Prerpints.org logo
Preprint
Review

This version is not peer-reviewed.

Neurotoxicity Biochemical Biomarkers in Fish Toxicology

Submitted:

20 September 2024

Posted:

20 September 2024

You are already at the latest version

Abstract
Acetylcholinesterase (AChE) activity is the most commonly used neurotoxicity biomarker in fish. It is measured mostly in the brain but can also be evaluated in muscle or (in the case of very small fish) in whole body homogenate. AChE activity is measured using standard methods, thus the results obtained by various authors are comparable. AChE seems to be a sensitive neurotoxicity biomarker since in most cases of fish exposure to various toxic agents a decrease in the enzyme activity was observed. The effects of toxic agents on AChE activity are concentration and time-related. An increase in AChE activity occurred very rarely. The results of the analysis showed that most aquatic pollutants may modulate AChE activity. Acetylcholinesterase activity can be also used to evaluate transgenerational neurotoxic effects.
Keywords: 
acetylcholinesterase
;  
AChE
;  
aquatic pollution
;  
fish
;  
neurotoxicity
Subject: 
Biology and Life Sciences  -   Toxicology

1. Introduction

Development and use of neurotoxicity biomarkers is an important issue in toxicology since numerous emerging pollutants such as microplastics, pharmaceuticals, and other novel chemical compounds as well as “old” contaminants e.g. metals and pesticides, show a neurotoxic potential and may cause human neurodevelopmental disorders such as autism, attention-deficit hyperactivity disorder, dyslexia and others [1]. In polluted waters, neurotoxic compounds affect aquatic organisms first, thus measurement of neurotoxic effects in fish is necessary from the One Health perspective [2]. Neurotoxicity in fish may result in disturbed schooling, migration, spatial distribution, feeding, reproduction, and predator avoidance. Neurotoxicity biomarkers used in fish include histopathological [3,4] and morphometric [5] evaluation of brain, various behavioral endpoints [6,7,8], expression of marker genes associated with neuron development and growth [9], the levels of neurotransmitters in brain [10,11]. However, changes in activity of cholinesterases are the most often used biomarkers of aquatic pollution, because these enzymes are frequent targets for toxic effects of contaminants such as insecticides or metals [12]. The most commonly used biochemical biomarker of neurotoxicity in fish is acetylcholinesterase (AChE) activity measured in the brain, in the whole body (in the case of embryos and larvae), or in other organs (muscle, liver, and gills).
The present paper aims to review and summarize the recent literature data on the use of acetylcholinesterase activity as a neurotoxicity biomarker.

2. Acetylcholinesterase as a Neurotoxicity Biomarker

AChE is a serine hydrolase that terminates the impulse transmission in cholinergic synapses by hydrolysis and inactivation of the neurotransmitter acetylcholine (ACh). Although the primary function of AChE is to terminate neural transmission, it was also found that AChE plays a role in neural development [13]. AChE occurs in all tissues and is most abundant in the brain and muscles. AChE inhibition increases ACh concentration and its neurotransmitter action [14] causing cognitive and behavioral disturbances. According to de la Torre et al. [15], AChE activity is a sensitive biomarker of exposure of fish to toxic agents. However, Menendez-Helman et al. [16] pointed out that using AChE activity as a biomarker requires understanding its natural fluctuation. They measured the seasonal cycle of AChE activity in Cnesterodon decemmaculatus and reported the highest values in summer, and a considerable decrease in winter, probably related to different water temperatures. Also, an inverse relationship between enzymatic activity and animal size was established. Seasonal changes in AChE activity and sensitivity to pesticides (glyphosate and chlorpyrifos) were also reported by Bernal-Rey et al. [17] for the same fish species.
Scopus database was searched for the effects of toxic agents on fish AChE activity (Article title, Abstract, Keywords: “fish AND toxic* AND acetylcholinesterase”). The search resulted in 1308 documents, including 881 (67%) published in 2014-2023 (Oct. 24, 2023). These data were viewed and 100 of them (concerning only the brain or, in the case of embryos and larvae, whole body AChE) were selected and shown in Table 1.
Additionally, the search: “fish AND pesticide AND acetylcholinesterase” resulted in 49% of papers published in the last 10 years, “fish AND pharmaceutical or drug” AND acetylcholinesterase - 61%, “fish AND nanoparticle AND acetylcholinesterase” - 86% and “fish AND microplastic AND acetylcholinesterase” resulted in 98% of papers published in 2014-2023. These statistics show that AChE activity measurement is an increasingly important component of multibiomarker evaluation of the effects of toxic agents in fish, including emerging aquatic pollutants.
In Table 1 summarizing the effects of various toxic agents on AChE activity, 100 papers were included containing 119 data (in some studies, toxicity of more than one compound was evaluated). Most data (45%) concern pesticides (35% – insecticides, 8% – herbicides, 2% – fungicides). Other groups of data concern pharmaceuticals and disinfectants (12%), elements (10%), microplastics (7%) and nanoparticles (6%). The remaining 18% of data describe the effects of other compounds such as antifouling agents, cosmetic components, aromatic hydrocarbons, cyanotoxins, plastic components, and others. Most experiments (44%) were conducted on embryos, larvae, or adults of Danio rerio.
Analysis of the methods of AChE activity measurements (in 100 papers) revealed that most authors (66%) used the method developed and described by Ellman et al. [18], 23% used commercial biochemical kits, 4% - other methods and 7% did not specify the method used. Spectrophotometric cuvettes (16%) are often replaced by microplates (27%) and 57% of authors did not specify the reading method (but commercial kit users presumably used microplates, thus the microplates were probably used in most studies).

3. The effects of Toxic Agents on Acetylcholinesterase Activity

Analysis of the results shown in Table 1 revealed that in most cases (64%) AChE inhibition was reported, in 25% - no change, and only in 11% - an increase in AChE activity occurred. In case of no significant change observed, most data (44%) concerned lower concentrations of agents, while at higher concentrations changes occurred, in 35% no change was a single result for one concentration tested or observed at all levels of a studied agent, in 18% - after shorter times of exposure, while at longer times changes were observed, and only in 3% (1 case) nonlinear reaction occurred and no change was reported at the intermediate concentration of an agent. These data showed clear concentration- and time-related effects of chemicals on AChE activity, and a high responsiveness and sensitivity of this enzyme to various toxic agents. This confirms that AChE is a good neurotoxicity biomarker.
The results of many studies indicate that various aquatic pollutants may modulate AChE activity in fish, e.g., organophosphorus and carbamate insecticides are well-known AChE inhibitors that act by specifically binding to the active site of AChE and blocking the access of the physiological substrate [14,19,20,21], as well as organophosphate esters used as plasticizers and flame retardants [22]. However, chemicals other than carbamates and organophosphates have also been documented to alter acetylcholinesterase activities (Table 1). Sato et al. [23] tested in vitro inhibition of common carp AChE by 35 various insecticides and their derivatives and found that various chemical forms of active compounds (e.g, oxon vs. thiono or diethyl vs dimethyl) showed different inhibitory power. Also, combinations of different insecticides showed an additive inhibitory effect. An in vitro study of the effects of metal ions on Diodon hystrix brain AChE activity [24] revealed inhibition order: Cr6+ < Co2+ < Ag2+ < Cu2+ < Pb2+ < As5+ < Cd2+ < Zn2+ < Ni2+ < Hg2+ and proved that AChE activity is a useful biomarker for evaluating metal toxicity to fish.
According to Colovic et al. [14], AChE inhibitors include irreversible and reversible groups. Reversible inhibitors, competitive or noncompetitive, mostly have therapeutic applications, while toxic effects are associated with irreversible AChE activity modulators.
The data of various studies showing the effects of aquatic pollutants on the fish brain or whole-body AChE activity (Table 1) reveal that most examined agents including microplastics, pharmaceuticals, pesticides, metals, etc., usually inhibited the enzyme but the effects were concentration- and time-related. AChE activation also sometimes occurred or non-linear alternate bidirectional changes were observed at various concentrations or different times of exposure to the same agent making interpretation of neurotoxic effect difficult. In most cases of microplastic exposures inhibition of AChE was observed, however at low concentrations enzyme activation sometimes occurred [25,26]. Also, most exposures of fish to pharmaceuticals resulted in AChE inhibition, except for some antidepressants (sertraline) that induced no changes or activated the enzyme. According to Muller et al. [27], antidepressants inhibited human AChE and opposite effects observed in fish are difficult to explain. Most pesticides: insecticides, herbicides, fungicides, and an antifouling agent caused AChE inhibition in fish, often concentration and/or time-related. According to Mladenovic et al. [28], many commonly used triazine, carbamate, organophosphate, neonicotinoid, methylurea, or phenylurea pesticides such as atrazine, simazine, propazine, carbofuran, monocrotophos, dimethoate, carbaryl, tebufenozide, imidacloprid, acetamiprid, diuron, monuron, and linuron are AChE inhibitors due to their binding to the AChE active site. For some pesticides that usually inhibited AChE, activation was reported in single cases [29,30,31] which might have been related to very low concentrations used. Inhibition of AChE activity by other chemicals was also reported: disinfectants, bisphenol A, cosmetic compounds, organic solvents, metals and other elements, nitrogenous metabolites, and other aquatic pollutants. It is noteworthy that in the case of exposure of fish to nanoparticle materials AChE activity was rarely inhibited, suggesting that environmentally relevant concentrations of these pollutants are little neurotoxic. According to the review by Olivares-Rubio and Espinosa-Aguirre [32], polycyclic aromatic hydrocarbons (e.g., benzo[a]pyrene, pyrene, and anthracene) inhibited AChE activity but PAHs with a low molecular weight did not induce changes or cause stimulation of AChE activity.
Acetylcholinesterase activity is sometimes measured in various tissues and the results are not always the same as for the brain and also differ among the organs examined. Fakhereddin and Doğan [33] observed different values and different time- and concentration-related patterns of splenic and cardiac AChE activities in rainbow trout treated with clothianidin (a neonicotinoid insecticide). Abegoda-Liyanageand Pathiratne [34] reported no alterations in brain AChE activities following TiO2 and nano-TiO2 exposures but an increase occurred in gill and liver. Different patterns of gill and muscle AChE activity changes over time of exposure to three pesticides, compared to the brain, were reported also by Amin et al. [29]. Bonansea et al. [35] observed no changes in brain AChE activity following low and high cypermethrin or chlorpyrifos exposures, while muscle AChE activities significantly decreased after exposures to high concentrations of both pesticides. According to Golombieski et al. [36], AChE activity in the brain and muscles of three cyprinid fish species exposed to diafuran decreased similarly. A considerable and significant decrease in AChE activity in muscle of trichlorfon-exposed tilapia was also reported by Guimaraes et al. [37]. Similar changes in brain and muscle AChE activities were observed by Modesto and Martinez [38] in Prochilodus lineatus exposed to Roundup and by Benli and Celik [39] in zebrafish treated with sulfoxaflor. The decrease in AChE activities measured in the muscle, liver, and gill of tilapia exposed to dichloromethane followed the decrease in the brain. However, the control value of AChE activity and the difference between the values for the control and exposed fish were the highest in brain and muscle. Nayak and Patnaik [40] reported the highest activity of AChE in the brain and muscle of Anabas testudineus but the degree of enzyme inhibition following exposure to naphthalene occurred also in the gill and liver. According to Tilton et al. [41], chlorpyrifos reduced zebrafish muscle AChE activity in a concentration-dependent way but no such a relationship was observed for copper – a significant decrease in AChE activity occurred only at the lowest Cu concentration (6.3 µg/L). Ullah et al. [42] reported similar activities and inhibition of brain and muscle AChE of Tor putitora from various sampling sites of different pollution levels. The results obtained by Marinho et al. [43] showed an even higher sensitivity of muscle AChE, compared to the brain, to nano-Ag intoxication. These data show that AChE activity in muscle is probably an equally reliable biomarker as brain or whole-body AChE activity.
On the other hand, sometimes brain and muscle AChE may show opposite reactions to toxic agents. dos Santos Teixeira et al. [44] reported that AChE activity of pintado da Amazônia decreased in muscle but increased in the brain compared to the control group after Roundup exposure. According to Zhang et al. [45], AChE activity in various tissues of zebrafish was inhibited almost at the same time when the fish were exposed to high concentrations of toxic agents (Cd2+ or deltamethrin), while at lower concentrations inhibition showed a delay compared to the brain: brain > gill > muscle > liver. These data show that muscle AChE activity should be considered with caution. Caution is also necessary since for some toxic agents, AChE may be not a reliable biomarker of neurotoxicity. Agostini et al. [46] reported no changes in zebrafish brain AChE activity during treatment with 0.5% ethanol solution, while a significant decrease in acetylcholine level and choline acetyltransferase occurred.
Table 1. The effects of toxic agents on brain (or whole body – in embryos and larvae) acetylcholinesterase (AChE) activity in fish.
Table 1. The effects of toxic agents on brain (or whole body – in embryos and larvae) acetylcholinesterase (AChE) activity in fish.
GCS Fish species Toxic agent Concentration [mg/L] Exp. dur. [d] AChE
activity 		Author
M Oreochromis niloticus microplastic 100 21 ↓ [47]
M Danio rerio embryos microplastic 0.1-10 4 ↓ [48]
M Oreochromis mossambicus microplastic 100***
500 *** 1000*** 		14 -
↓
↓ 		[49]
M Danio rerio embryos microplastic 0.1-3 5 ↓ [50]
M Danio rerio microplastic 10000@ 5 ↓ [51]
M Oryzias javanicus microplastic 0.5-5 21 ↑ [25]
M
E 		Danio rerio microplastic 2 30 ↑ [26]
Cu (as CuSO4•5H2O) 25* ↑
M
E 		Dicentrarchus labrax microplastic 0.26 or 0.69 4 ↓ [52]
Hg (as HgCl2) 0.010 or 0.016 ↓
E Cnesterodon decemmaculatus As (as NaAsO2) 0.5-5 4 - [53]
E Anabas testudineus Cr VI (as CrO3) 2.75 or 5.5 72 ↓ [54]
E
E 		Danio rerio Cr III (as CrCl3•6H2O)
Cr VI (as (K2Cr2O7) 		1 5 ↓

↓ 		[55]
E Hypopthalmichthys molitrix larvae Hg (as HgCl2) 1-10* 14 ↓ [56]
E Danio rerio embryos Hg (as HgCl2) 10

100 		1
2-4
1
2-4 		-
-
-
↓ 		[57]
E Danio rerio Al 5.5 15 ↓ [58]
E Oreochromis niloticus Al (as Al2(SO4)3 1 or 3* 14 ↑ [59]
E Danio rerio embryos + larvae Sb (as K2Sb2C8H4O12•3 H2O) 200-800 2 ↓ [60]
N
E 		Oreochromis niloticus Ti (as TiO2 NPs)
Ti (as TiO2) 		0.05 or 0.1 7-14 -
- 		[34]
N
N
N
N 		Oncorhynchus mykiss graphene nanoflakes graphene oxide
reduced graphene oxide silicon carbide nanofibers 		4 36 - [61]
N Danio rerio Se NPs 0.5 or 10 4 ↓ [62]
N Danio rerio Ag NPs 1
3-5* 		4 -
↓ 		[43]
F Danio rerio paclobutrazol 10 4-14 ↓ [63]
F Danio rerio thifuzamide 0.19
1.9 or 2.85 		6 ↓ [64]
F Danio rerio embryos mancozeb 0.5*
5*
50* 		4 ↓
-
↓ 		[65]
H Prochilodus lineatus Roundup® 1 or 5 4 ↓ [38]
H Danio rerio larvae Roundup® 4.8* 5 ↑ [30]
H Danio rerio embryos Roundup®
glyphosate 		0.25 2 ↓ [66]
H Danio rerio larvae haloxyfop-p-methyl 0.2-0.4 4 ↑ [67]
H Oreochromis niloticus pendimethalin 0.52 28 ↓ [68]
I
H 		Cyprinus carpio chlorpyrifos
glyphosate 		25*
3.5 		21 ↓
↓ 		[69]
I
I
H 		Tilapia nilotica Nemacur®
malathion
diuron 		0.1-2
0.1-2
1 		1 ↓
↓
↓ 		[70]
H
I 		Danio rerio DMA® 806 BR (Fipronil)
Regent® 800 WG (2,4-D) 		63.5*
447* 		4 ↑
↑ 		[71]
I Danio rerio embryos chlorphoxim 2.5-7.5 4 ↓ [72]
I Gambusia affinis chlorpyrifos 0. 297 4 ↓ [73]
I Oncorhynchus mykiss chlorpyrifos 2.25 or 4.5
7.25*
7.25* 		1-4
1-2
3-4 		-
-
↓ 		[74]
I Oreochromis niloticus chlorpyrifos 5-15* 30 ↓ [75]
I Cyprinus carpio
Ctenopharyngodon idella
Aristychthysnobilis 		diafuran 1-3 4 ↓ [36]
I
I 		Jenynsia multidentata cypermethrin
chlorpyrifos 		0.04 or 0.4*
0.4 or 4* 		4 -
- 		[35]
I Gambusia affinis cypermethrin 0.2 or 6.25** 7 ↓ [76]
I Heteropneustes fossilis chlorpyrifos 0.09 or 0.192 7-30 ↓ [77]
I Capoeta umbla chlorpyrifos 55

110
1
4
1
4 		-
↓
↓
↓ 		[4]
I Cyprinus carpio chlorpyrifos 23 or 46* 14 ↓ [78]
I

I

I 		Oreochromis niloticus malathion

chlorpyrifos

λ-cyhalothrin
1.425

0.125

0.0039
1
2
1
2
1
2 		↑
↓
↑
↑
-
↓ 		[29]
I Colossoma macropomum malathion 7.3 4 - [79]
I Cyprinus carpio λ cyhalothrin 0.14 or 0.28* 15-45 ↓ [80]
I
I 		Danio rerio chlorpyrifos
cyfluthrin 		1.16*
7.06 or 14.12* 		5 ↓ [81]
I Oncorhynchus mykiss larvae chlorpyrifos 0.3*
3* 		21 -
↓ 		[82]
I Oncorhynchus mykiss chlorpyrifos 2*

4*
6* 		7
14-21
7-21
7-21 		-
↓
↓
↓ 		[83]
I Danio rerio dinotefuran 0.2
1 		28 ↓
↓ 		[84]
I Danio rerio imidacloprid 0.15*
15 or 45* 		4 -
↓ 		[85]
I
I 		Danio rerio imidacloprid
thiamethoxam 		0.05-20* 14-35 -
↓ 		[86]
I Danio rerio sulfoxaflor 0.87-3.51 4 ↑ [39]
I Gambusia affinis carbofuran 0.191 or 0.255 15-40 ↓ [87]
I Oreochromis niloticus carbofuran 0.246 30 ↓ [88]
I Danio rerio larvae fenpropathrin 0.016-0.064 4 ↑ [89]
I Danio rerio larvae isoprocarb 1-2.5 6 ↓ [90]
I Clarias batrachus thiamethoxam 6.93 or 13.86 45 ↓ [91]
I Danio rerio methomyl 0.5-23.3 6 ↓ [92]
I Oncorhynchus mykiss phosmet 5*
5*
25 or 50* 		1-2
3-4
1-4 		-
↓
↓ 		[93]
I Prochilodus lineatus fipronil 5.5
82^ 		15 -
↓ 		[94]
I Rhamdia quelen trichlorfon 11 21 ↓ [95]
I Colossoma macropomum trichlorfon 0.26 or 0.43 1-4 ↓ [96]
I Carassius auratus gibelio trichlorfon 0.5-2**** 0.5-4 ↓ [97]
I Oryzias latipes diazinon 10 or 20* 122 ↓ [98]
I
I 		Channa punctatus triazophos
deltamethrin 		3.4 or 6.8*
0.36 or 0.72* 		4 ↓
↓ 		[99]
Pd Danio rerio embryos + larvae cloramine T 16
32
64
128 		4 -
-
↓
↓ 		[100]
Pd Danio rerio embryos + larvae 2, 5-dichloro-1, 4-benuinone 0.2
0.4 or 0.6 		4 -
↓ 		[101]
Pd Danio rerio fluoxetine 5-16** 4 ↓ [102]
Pd Danio rerio fluoxetine 0.1-10* 21 - [103]
Pd Rhamdia quelen ciprofloxacin 1*
10 or 100* 		28 -
↓ 		[3]
Pd Oreochromis mossambicus triclosan 0.131-1.046 4 ↓ [104]
Pd Corydoras paleatus triclosan 189* 2 ↓ [105]
Pd Gambusia affinis gestodene 4.4**
378.7** 		60 ↓
↑ 		[106]
Pd Oreochromis niloticus synthetic progesterone 0.2-0.8 4 ↓ [107]
Pd Danio rerio metformin 1, 20 or 40* 120 ↓ [108]
Pd Danio rerio sertraline 1
10 or 100 		28 -
↑ 		[109]
Pd Danio rerio embryos + larvae sertraline 1-100 10 - [64]
Pd Danio rerio nortriptyline 0.88-500* 7 ↓ [110]
Pd Danio rerio embryos moxidectin 1.5-5* 4 - [111]
O Danio rerio tributylin 10**
100-300** 		42 -
↓ 		[112]
O Danio rerio embryos bisphenol A 11.4 1 ↓ [113]
O Danio rerio bisphenol A 0.22-1.5* 4 ↑ [31]
O Danio rerio bisphenol AF 0.05 or 0.5 4 ↓ [114]
O Gambusia affinis bisphenol A 4.74 or 7.74 15-60 ↓ [115]
O Oreochromis niloticus benzylparaben 0.005-5* 56 ↓ [116]
O Danio rerio embryos methylparaben 0.1 or 1* 6 ↓ [117]
O Danio rerio methylparaben 1 or 11* 30 ↓ [118]
O Danio rerio embryos octocrylene 5*
50 or 500* 		4 -
↓ 		[119]
O Gambusia affinis decabromodiphenyl ether 25 or 50* 2 ↑ [120]
O Danio rerio embryos benzophenone-3 1 or 10* 3 ↓ [121]
O

O 		Danio rerio larvae hexabromobenzene

pentabromobenzene
30*
100-300*
30-100*
300* 		6 -
↓
-
↓ 		[122]
O
O
O 		Clarias gariepinus benzene
toluene
xylene 		0.762**
26.614**
89.403** 		30 ↓
-
- 		[123]
O Anabas testudineus naphthalene 4.2-5.0 3 ↓ [40]
O
O 		Cyprinus carpio ammonia NH3
nitrite NO2- 		30.7
153.7 		4 ↓ [124]
O Danio rerio embryos + larvae ammonia NH3 0.06-0.85 7 ↓ [125]
O Oreochromis mossambicus ammonia NH3 1 28-56 ↓ [126]
O Oreochroms niloticus guanitoxin 125 or 250# 4 ↓ [127]
O Danio rerio ethanol 5 7-28 - [46]
O Oreochromis mossambicus dichloromethane 730-790 4 ↓ [128]
O Cirrhinus mrigala phenol 2.32 or 6.96 7-28 ↓ [129]
O Clarias gariepinus burnt tyre ash 0.56-2.24 28 ↓ [130]
*µg/L **ng/L ***mg/kg feed ****g/kg feed #algal extract @particles/L ^ µg/kg sediment . GCS – group of chemical substance; E – metals and other elements; F – fungicides; H – herbicides; I – insecticides; M – microplastics; N – nanoparticles; O – other substances; Pd – pharmaceuticals and disinfectants . Exp. dur. – exposure duration; d – days; m – minutes; n/a – not applicable; NPs – nanoparticle. ↓ – decrease, ↑ – increase, - – no change.

4. Transgenerational Effects of Toxic Agents on Acetylcholinesterase Activity

Interestingly, AChE activity can be used as a biomarker of transgenerational toxicity effects. Pompermaier et al. (2022) reported that zebrafish larvae obtained from adults exposed to an herbicide containing 2,4- dichlorophenoxyacetic acid (2,4-D) showed elevated AChE activity. According to Wan et al. (2022), parental exposure of medaka to benzo[a]pyrene (BaP) caused a significant reduction of AChE activity in offspring but not in the exposed adults. Molecular analysis revealed that the marker genes associated with neuron development were downregulated in the larvae. This indicates an epigenetic effect. A similar transgenerational epigenetic effect of chlorpyrifos-oxon on AChE activity was observed by Schmitt et al. [131]. According to Brander et al. [132], epigenetic mechanisms include acetylation or phosphorylation of histones, DNA methylation, and interactions of non-coding RNA during transcription that may affect gene and protein expression.
Inhibition of AChE activity is usually accompanied by oxidative stress. Issac et al. [133] found that oxidative stress experimentally induced by exposure of zebrafish embryos to H2O2 resulted in a considerable and significant decrease in AChE activity. However, the role of oxidative stress in the modulation of AChE activity is still unclear and according to various authors, it may be involved in both decrease [134,135] and increase [136] of AChE activity.

5. Other neurotoxicity Biochemical Biomarkers

In fish toxicology, other neurotoxicity biochemical biomarkers are also sometimes used such as activities of BChE (butyrylcholinesterase), CbE (carboxylesterase), and GABA (γ-aminobutyric acid) level [137]. Morsy [10] evaluated the concentrations of neurotransmitters: dopamine, norepinephrine, and acetylcholine in Cyprinus carpio, exposed to dithiopyridine herbicide, and reported a decrease in catecholamine levels, while ACh concentration increased (which was accompanied by AChE inhibition). Bedrossiantz et al. (2021) reported a concentration- and time-dependent decrease in the brain levels of dopamine, norepinephrine, and serotonin in zebrafish exposed to methamphetamine. According to a meta-analysis by Santana et al. [138], fish ChE and BChE are common biomarkers of environmental contamination due to their sensitivity to many toxicants, including pesticides. The authors concluded that regardless of tissue, BChE response was more variable than AChE, and no difference between their average activities was detected. The effects of pesticides were size- and age-related, cholinesterases in adult fish being the least sensitive to intoxication. Insecticides were stronger inhibitors compared to herbicides and fungicides. Interestingly, the analytical-grade pure active compounds inhibited cholinesterase activities more than commercial formulations. Among the pesticide classes, organophosphorus insecticides had the strongest effect on the activity of fish AChE and BChE, followed by carbamates, organochlorines, and pyrethroids. Ortiz-Delgado et al. [139] reported that malathion inhibited AChE and BChE activities in Senegalese sole in a dose- and time-dependent manner, but the activity of BChE was about two orders of magnitude lower compared to AChE.

6. Conclusions

The activity of acetylcholinesterase is the most widely applied neurotoxicity biomarker in fish. The results obtained by many authors for various fish species and numerous chemicals showed that AChE activity is a sensitive, and useful but nonspecific biomarker of intoxication in fish. AChE activity can be affected by aquatic pollutants, that mostly cause enzyme inhibition. This results in disturbed acetylcholine hydrolysis, the consequences of which are disturbed sensory, cognitive, and motor functions.

References

  1. Stengel, D.; Wahby, S.; Braunbeck, T. In search of a comprehensible set of endpoints for the routine monitoring of neurotoxicity in vertebrates: Sensory perception and nerve transmission in zebrafish (Danio rerio) embryos. Environ. Sci. Pollut. Res. 2018, 25, 4066–4084. [Google Scholar] [CrossRef] [PubMed]
  2. https://www.who.int/europe/initiatives/one-health.
  3. Carvalho, P.S.; Fonseca-Rodrigues, D.; Pacheco, M.; Almeida, A.; Pinto-Ribeiro, F.; Pereira, P. Comparative neurotoxicity of dietary methylmercury and waterborne inorganic mercury in fish: Evidence of optic tectum vulnerability through morphometric and histopathological assessments. Aquat. Toxicol. 2023, 261, 106557. [Google Scholar] [CrossRef] [PubMed]
  4. Kirici, M. Assessment of 8-hydroxy-2-deoxyguanosine activity, apoptosis, acetylcholinesterase and antioxidant enzyme activity in Capoeta umbla brain exposed to chlorpyrifos. Int. J. Ocean. Hydrobiol. 2022, 51, 167–177. [Google Scholar] [CrossRef]
  5. Puga, S.; Pereira, P.; Pinto-Ribeiro, F.; O’Driscoll, N.J.; Mann, E.; Barata, M.; Pousão-Ferreira, P.; Canário, J.; Almeida, A.; Mário Pacheco. Unveiling the neurotoxicity of methylmercury in fish (Diplodus sargus) through a regional morphometric analysis of brain and swimming behavior assessment. Aquat. Toxicol. 2016, 180, 320–333. [Google Scholar] [CrossRef] [PubMed]
  6. Sanchez-Aceves, L.M.; Pérez-Alvarez, I.; Belén Onofre-Camarena, D.; Gutiérrez-Noya, V.M.; Rosales-Pérez, K.E.; Orozco-Hernández, J.M.; Hernández-Navarro, M.D.; Islas Flores, H.; Gómez-Olivan, L.M. Prolonged exposure to the synthetic glucocorticoid dexamethasone induces brain damage via oxidative stress and apoptotic response in adult Danio rerio. Chemosphere 2024, 364. [Google Scholar] [CrossRef] [PubMed]
  7. Chang, X.; Shen, Y.; Yang M; Yun L. ; Liu Z.; Feng S.; Yang G.; Meng X.; Su X. Antipsychotic drug-induced behavioral abnormalities in common carp: The potential involvement of the gut microbiota-brain axis. J. Hazard. Mat. 2024, 472, 134444. [Google Scholar] [CrossRef]
  8. Oger, M.J.L.; Vermeulen, O.; Lambert, J.; Madanu, T.L.; Kestemont, P.; Cornet, V. Down to size: Exploring the influence of plastic particle Dimensions on physiological and nervous responses in early-stage zebrafish. Environ. Pollut. 2024, 351, 124094. [Google Scholar] [CrossRef]
  9. Wan, T.; Au, D. W-T.; Mo J.; Chen L.; Cheung K-M.; Kong R.Y-C.; Seemann F. Assessment of parental benzo[a]pyrene exposure induced cross-generational neurotoxicity and changes in offspring sperm DNA methylome in medaka fish. Environ. Epigen. 2022, 8, 1–12. [Google Scholar] [CrossRef]
  10. Morsy, G.M. Bioaccumulation and neurotoxicity of dithiopyridine herbicide in the brain of freshwater fish, Cyprinus carpio. Toxicol. Indust. Health 2013, 31. [Google Scholar] [CrossRef]
  11. Bedrossiantz, J.; Bellot, M.; Dominguez-García, P.; Faria, M.; Prats, E.; Gómez-Canela, C.; López-Arnau, R.; Escubedo, E.; Raldúa, D. A zebrafish model of neurotoxicity by binge-like methamphetamine exposure. Front. Pharmacol. 2021, 12, 770319. [Google Scholar] [CrossRef]
  12. Vieira, M.; Nunes, B. Cholinesterases of marine fish: Characterization and sensitivity towards specific chemicals. Environ. Sci. Pollut. Res. 2021, 28, 48595–48609. [Google Scholar] [CrossRef]
  13. Bigbee, J.W.; Sharma, K.W.; Gupta, J.J.; Dupree, J.L. Morphogenic role for acetylcholinesterase in axonal outgrowth during neural development. Environ. Health Perspect. 1999, 107, Suppl. 1. 81–87. [Google Scholar]
  14. Colovic, M.B.; Krstic, D.Z.; Lazarevic-Pasti, T.D.; Bondzic, A.M.; Vasic, V.M. Acetylcholinesterase inhibitors: Pharmacology and toxicology. Curr. Neuropharmacol. 2013, 11, 315–335. [Google Scholar] [CrossRef] [PubMed]
  15. de la Torre, F.R.; Ferrari, L.; Salibian, A. Freshwater pollution biomarker: Response of brain acetylcholinesterase activity in two fish species. Comp. Biochem. Physiol. C 2002, 131, 271–280. [Google Scholar] [CrossRef] [PubMed]
  16. Menéndez-Helman, R.J.; Ferreyroa, G.V.; dos Santos Afonso, M.; Salibián, A. Circannual rhythms of acetylcholinesterase (AChE) activity in the freshwater fish Cnesterodon decemmaculatus. Ecotoxicol. Environ. Saf. 2015, 111, 236–241. [Google Scholar] [CrossRef] [PubMed]
  17. Bernal-Rey, D.L.; Cantera, C.G.; dos Santos Afonso, M.; Menéndez-Helman, R.J. Seasonal variations in the dose-response relationship of acetylcholinesterase activity in freshwater fish exposed to chlorpyrifos and glyphosate. Ecotoxicol. Environ. Saf. 2020, 187, 109673. [Google Scholar] [CrossRef]
  18. Ellman, G.L.; Courtney, K.D.; Andres V., J.R.; Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinestarase activity. Biochem. Pharmacol. 1961, 7, 88–95. [Google Scholar] [CrossRef]
  19. Fulton, M.H.; Key, P.B. Acetylcholinesterase inhibition in estuarine fish and invertebrates as an indicator of organophosphorus insecticide exposure and effects. Environ. Toxicol. Chem. 2001, 20, 37–45. [Google Scholar] [CrossRef]
  20. Rodríguez-Fuentes, G.; Rubio-Escalante, F.J.; Noreña-Barroso, E.; Escalante-Herrera, K.S.; Schlenk, D. Impacts of oxidative stress on acetylcholinesterase transcription, and activity in embryos of zebrafish (Danio rerio) following Chlorpyrifos exposure. Comp. Biochem. Physiol. C 2015, 172–173, 19–25. [Google Scholar] [CrossRef]
  21. Arora, S.; Kumar, A. Mixture toxicity assessment of selected insecticides to silver perch fingerling, Bidyanus bidyanus. Ecotoxicol. Environ. Saf. 2021, 226, 112790. [Google Scholar] [CrossRef]
  22. Patisaul, H.B.; Behl, M.; Birnbaum, L.S.; Blum, A.; Diamond, M.L.; Fernández, S.R.; Hogberg, H.T.; Kwiatkowski, C.F.; Page, J.D.; Soehl, A.; Stapleton, H.M. Beyond cholinesterase inhibition: Developmental neurotoxicity of organophosphate ester flame retardants and plasticizers. Environ. Health Perspect. 2021, 129, 105001. [Google Scholar] [CrossRef] [PubMed]
  23. Sato, R.; Mitani, K.; Matsumoto, T.; Takahashi, S.; Yamada R-H. ; Kera Y. Effects of insecticides in vitro on acetylcholinesterase purified from body muscle of Koi carp (Cyprinus carpio). Jap. J. Environ. Toxicol. 2007, 10, 1–38. [Google Scholar]
  24. Nordin, N.; Abdulla, R. ; S.A.; Sabullah M.K. Acetylcholinesterase (AChE) of Diodon hystrix brain as an alternative biomolecule in heavy metals biosensing. J. App. Sci. Engin, 2021; 25, 573–580. [Google Scholar] [CrossRef]
  25. Usman, S.; Razis, A.F.A.; Shaari, K.; Amal, M.N.A.; Saad, M.Z.; Isa, N.M.; Nazarudin, M.F. Polystyrene microplastics exposure: An insight into multiple organ histological alterations, oxidative stress and neurotoxicity in Javanese medaka fish (Oryzias javanicus Bleeker, 1854). Int. J. Environ. Res. Pub. Health 2021, 18, 9449. [Google Scholar] [CrossRef] [PubMed]
  26. Santos, D.; Luzio, A.; Felix, L.; Cabecinha, E.; Bellas, J.; Monteiro, S.M. Microplastics and copper induce apoptosis, alter neurocircuits, and cause behavioral changes in zebrafish (Danio rerio) brain. Ecotoxicol. Environ. Saf. 2022, 242, 113926. [Google Scholar] [CrossRef]
  27. Muller, T.C.; Rocha, J.B.T.; Morsch, V.M.; Neis, R.T.; Schetinger, M.R.C. Antidepressants inhibit human acetylcholinesterase and butyrylcholinesterase activity. Biochim. Biophys. Acta 2002, 1587, 92–98. [Google Scholar] [CrossRef]
  28. Mladenovic, M.B.; Arsic, B.B.; Ragno, R.; Stankovic, N.; Mihovic, N.; Regan, A.; Milicevic, J.S.; Micic, R. The targeted pesticides as acetylcholinesterase inhibitors: Comprehensive cross-organism molecular modelling studies performed to anticipate the pharmacology of harmfulness to humans in vitro. Molecules 2018, 23, 2192. [Google Scholar] [CrossRef]
  29. Amin, M.; Yousuf, M.; Attaullah, M.; Ahmad, N.; Nor Azra, M.; Lateef, M.; Dad Buneri, I.; Zekker, I.; El-Saber Batiha, G.; Aboelenin, S.M.; Zahoor, M.; Ikram, M.; Naeem, M. Cholinesterase activity as a potential biomarker for neurotoxicity induced by pesticides in vivo exposed Oreochromis niloticus (Nile tilapia): Assessment tool for organophosphates and synthetic pyrethroids. Environ. Technol. 2023, 44, 2148–2156. [Google Scholar] [CrossRef]
  30. Pompermaier, A.; Tamagno, W.A.; Alves, C.; Barcellos, L.J.G. Persistent and transgenerational effects of pesticide residues in zebrafish. Comp. Biochem. Physiol. C 2022, 262, 109461. [Google Scholar] [CrossRef]
  31. Heredia-García, G.; Elizalde-Velázquez, G.A.; Gómez-Oliván, L.M.; Islas-Flores, H.; García-Medina, S.; Galar-Martínez, M.; Dublán-García, O. Realistic concentrations of Bisphenol-A trigger a neurotoxic response in the brain of zebrafish: Oxidative stress, behavioral impairment, acetylcholinesterase inhibition, and gene expression disruption. Chemosphere 2023, 330, 138729. [Google Scholar] [CrossRef]
  32. Olivares-Rubio, H.F.; Espinosa-Aguirre, J.J. Acetylcholinesterase activity in fish species exposed to crude oil hydrocarbons: A review and new perspectives. Chemosphere 2021, 264, 128401. [Google Scholar] [CrossRef]
  33. Fakhereddin, T.; Doğan, D. Pro-oxidant potency of clothianidin in rainbow trout. Arch. Indust. Hyg. Toxicol. 2021, 72, 164–172. [Google Scholar] [CrossRef] [PubMed]
  34. Abegoda-Liyanage, C.S.; Pathiratne, A. Comparison of toxicity of nano and bulk titanium dioxide on Nile tilapia (Oreochromis niloticus): Acetylcholinesterase activity modulation and DNA damage. Bull. Environ. Contam. Toxicol. 2023, 110, 101. [Google Scholar] [CrossRef] [PubMed]
  35. Bonansea, R.I.; Wunderlin, D.A.; Amé, M.V. Behavioral swimming effects and acetylcholinesterase activity changes in Jenynsia multidentata exposed to chlorpyrifos and cypermethrin individually and in mixtures. Ecotoxicol. Environ. Saf. 2016, 129, 311–319. [Google Scholar] [CrossRef] [PubMed]
  36. Golombieski, J.I.; MarchesanE. ; Rabaioli Camargo E.; Salbego J.; Schmitt Baumart J.; Loro V.L.; de Oliveira Machado S.L.; Zanella R.; Baldisserotto B. Acetylcholinesterase enzyme activity in carp brain and muscle after acute exposure to diafuran. Sci. Agric. (Piracicaba, Brazil) 2008, 65, 340–345. [Google Scholar] [CrossRef]
  37. Guimaraes, A.T.B.; Silva de Assisb, H.C.; Boeger, W. The effect of trichlorfon on acetylcholinesterase activity and histopathology of cultivated fish Oreochromis niloticus. Ecotoxicol. Environ. Saf. 2007, 68, 57–62. [Google Scholar] [CrossRef]
  38. Modesto, K.A.; Martinez, C.B.R. Effects of RoundupTransorb on fish: Hematology, antioxidant defenses and acetylcholinesterase activity. Chemosphere 2010, 81, 781–787. [Google Scholar] [CrossRef]
  39. Benli, P.P.; Çelik, M. In vivo effects of neonicotinoid-sulfoximine insecticide sulfoxaflor on acetylcholinesterase activity in the tissues of zebrafish (Danio rerio). Toxics 2021, 9, 73. [Google Scholar] [CrossRef]
  40. Nayak, S.; Patnaik, L. Acetylcholinesterase, as a potential biomarker of naphtalene toxicity in different tissues of a freshwater teleost, Anabas testudineus. J. Environ. Engin. Landsc. Manag. 2021, 29, 403–409. [Google Scholar] [CrossRef]
  41. Tilton, F.A.; Bammler, T.K.; Gallagher, E.P. Swimming impairment and acetylcholinesterase inhibition in zebrafish exposed to copper or chlorpyrifos separately, or as mixtures. Comp. Biochem. Physiol. C 2011, 153, 9–16. [Google Scholar] [CrossRef]
  42. Ullah, S.; Li, Z.; Hassan, S.; Ahmad, S.; Guo, X.; Wanghe, K.; Nabi, G. Heavy metals bioaccumulation and subsequent multiple biomarkers based appraisal of toxicity in the critically endangered Tor putitora. Ecotoxicol. Environ. Saf. 2021, 228, 113032. [Google Scholar] [CrossRef]
  43. Marinho, C.S.; Matias, M.V.F.; Toledo, E.K.M.; Smaniotto, S.; Ximenes-da-Silva, A.; Tonholo, J.; Santos, E.L.; Machado, S.S.; Zanta, C.L.P.S. Toxicity of silver nanoparticles on different tissues in adult Danio rerio. Fish Physiol. Biochem. 2021, 47, 239–249. [Google Scholar] [CrossRef] [PubMed]
  44. dos Santos Teixeira, J.M.; da Silva Lima, V.; de Moura, F.R.; da Costa Marisco, P.; Sinhorin, A.P.; Gindri Sinhorin, V.D. Acute toxicity and effects of Roundup Original® on pintado da Amazônia. Environ. Sci. Pollut. Res. 2018, 2018 25, 25383–25389. [Google Scholar] [CrossRef]
  45. Zhang, T.; Yang, M.; Pan, H.; Li, S.; Ren, B.; Ren, Z.; Xing, N.; Qi, L.; Ren, Q.; Xu, S.; Song, J.; Ma, J. Does time difference of the acetylcholinesterase (AChE) inhibition in different tissues exist? A case study of zebra fish (Danio rerio) exposed to cadmium chloride and deltamethrin. Chemosphere 2017, 168, 908–916. [Google Scholar] [CrossRef] [PubMed]
  46. Agostini, J.F.; Zuehl Dal Toé, H.C.; Medeiros Vieira, K.; Baldin, S.L.; Fernandes Costa, N.L.; Uribe Cruz, C.; Longo, L.; Machado, M.M.; da Silveira, T.R.; Schuck, P.F.; Pacheco Rico, E. Cholinergic system and oxidative stress changes in the brain of a zebrafish model chronically exposed to ethanol. Neurotoxicol. Res. 2018, 33, 749–758. [Google Scholar] [CrossRef] [PubMed]
  47. Yang, J.; Karbalaei, S.; Hussein, S.M.; Ahmad, A.F.; Walker, T.R.; Salimi, K. Biochemical effects of polypropylene microplastics on red tilapia (Oreochromis niloticus) after individual and combined exposure with boron. Environ. Sci. Eur. 2023, 35, 71. [Google Scholar] [CrossRef]
  48. Suman, A.; Mahapatra, A.; Gupta, P.; Ray, S.S.; Singh, R.K. Polystyrene microplastics modulated bdnf expression triggering neurotoxicity via apoptotic pathway in zebrafish embryos. Comp. Biochem. Physiol. C 2023, 271, 109699. [Google Scholar] [CrossRef]
  49. Jeyavani, J.; Sibiya, A.; Stalin, T.; Vigneshkumar, G.; Al-Ghanim, K.A.; Riaz, M.N.; Govindarajan, M.; Vaseeharan, B. Biochemical, genotoxic and histological implications of polypropylene microplastics on freshwater fish Oreochromis mossambicus: An aquatic eco-toxicological assessment. Toxics 2023, 11, 282. [Google Scholar] [CrossRef]
  50. Martin-Folgar, R.; Torres-Ruiz, M.; de Alba, M.; Cañas-Portilla, A.I.; González, M.C.; Morales, M. Molecular effects of polystyrene nanoplastics toxicity in zebrafish embryos (Danio rerio). Chemosphere 2023, 312, 137077. [Google Scholar] [CrossRef]
  51. Xue Y-H. ; Jia T.; Yang N.; Sun Z-X.; Xu Z-Y.; Wen X-L.; Feng L-S. Transcriptome alterations in zebrafish gill after exposure to different sizes of microplastics. J. Environ. Sci. Health A 2022, 57, 347–356. [Google Scholar] [CrossRef]
  52. Barboza, L.G.A.; Vieira, L.R.; BrancoV. ; Figueiredo N.; Carvalho F.; Carvalho C.; Guilhermino L. Microplastics cause neurotoxicity, oxidative damage and energy-related changes and interact with the bioaccumulation of mercury in the European seabass, Dicentrarchus labrax (Linnaeus, 1758). Aquat. Toxicol. 2018, 195, 49–57. [Google Scholar] [CrossRef]
  53. González Núñez, A.A.; Ferro, J.P.; Campos, L.B.; Eissa, B.L.; Mastrángelo, M.M.; Ferrari, L.; Ossana, N.A. Evaluation of the acute effects of arsenic on adults of the neotropical native fish Cnesterodon decemmaculatus using a set of biomarkers. Environ. Toxicol. Chem. 2022, 41, 1246–1259. [Google Scholar] [CrossRef] [PubMed]
  54. Kumar, N.; Bhushan, S.; Patole, P.B.; Gite, A. Multi-biomarker approach to assess chromium, pH and temperature toxicity in fish. Comp. Biochem. Physiol. C 2022, 254, 109264. [Google Scholar] [CrossRef] [PubMed]
  55. Xu, Y.; Wang, L.; Zhu, J.; Jiang, P.; Zhang, Z.; Li, L.; Wu, Q. Chromium induced neurotoxicity by altering metabolism in zebrafish larvae. Ecotoxicol. Environ. Saf. 2021, 228, 112983. [Google Scholar] [CrossRef] [PubMed]
  56. Wang, S.; Han, X.; Yu, T.; Liu, Y.; Zhang, H.; Mao, H.; Hu, C.; Xu, X. Isoprocarb causes neurotoxicity of zebrafish embryos through oxidative stress-induced apoptosis. Ecotoxicol. Environ. Saf. 2022, 242, 113870. [Google Scholar] [CrossRef]
  57. Henriques, M.C.; Carvalho, I.; Santos, C.; Herdeiro, M.T.; Fardilha, M.; Pavlaki, M.D.; Loureiro, S. Unveiling the molecular mechanisms and developmental consequences of mercury (Hg) toxicity in zebrafish embryo-larvae: A comprehensive approach. Neurotoxicol. Teratol. 2023, 100, 107302. [Google Scholar] [CrossRef]
  58. Alves, C.; Tamagno, W.A.; Vanin, A.P. , Pompermaier A.; Gil Barcellos L.J. Cannabis sativa-based oils against aluminum-induced neurotoxicity. Sci. Rep. 2023, 13, 813. [Google Scholar] [CrossRef]
  59. Oliveira, V.M.; Assis, C.R.D.; Silva Costa, C.M.; Silva, R.P.F.; Santos, J.F.; Carvalho Jr, L.B.; Bezerra, R.S. Aluminium sulfate exposure: A set of effects on hydrolases from brain, muscle and digestive tract of juvenile Nile tilapia (Oreochromis niloticus). Comp. Biochem. Physiol. C 2017, 191, 101–108. [Google Scholar] [CrossRef]
  60. Xia, S.; Zhu, X.; Yan, Y.; Zhang, Y.; Chen, G.; Lei, D.; Wang, G. Developmental neurotoxicity of antimony (Sb) in the early life stages of zebrafish. Ecotoxicol. Environ. Saf. 2021, 218, 112308. [Google Scholar] [CrossRef]
  61. Jakubowska-Lehrmann, M.; Dąbrowska, A.; Białowąs, M.; Makaras, T.; Hallmann, A.; Urban-Malinga, B. The impact of various carbon nanomaterials on the morphological, behavioural, and biochemical parameters of rainbow trout in the early life stages. Aquat. Toxicol. 2023, 259, 106550. [Google Scholar] [CrossRef]
  62. Fan, S.; Yang, Y.; Sun, L.; Yu, B.; Dai, C.; Yuanyuan, Q. Different toxicity to liver and gill of zebrafish by selenium nanoparticles derived from bio/chemical methods. Environ. Sci. Pollut. Res. 2022, 29, 61512–61521. [Google Scholar] [CrossRef]
  63. Guo, D.; Luo, L.; Kong, Y.; Kuang, Z.; Wen, S.; Zhao, M.; Zhang, W.; Fan, J. Enantioselective neurotoxicity and oxidative stress effects of paclobutrazol in zebrafish (Danio rerio). Pest. Biochem. Physiol. 2022, 185, 105136. [Google Scholar] [CrossRef] [PubMed]
  64. Yang, H.; Chen, H.; Liang, X.; Zhao, Y.; Martyniuk, C.J. Molecular and behavioral responses of zebrafish embryos/larvae after sertraline exposure. Ecotoxicol. Environ. Saf. 2021, 208, 111700. [Google Scholar] [CrossRef] [PubMed]
  65. Vieira, R.; Venâncio, C.A.S.; Félix, L.M. Toxic effects of a mancozeb-containing commercial formulation at environmental relevant concentrations on zebrafish embryonic development. Environ. Sci. Pollut. Res. 2020, 27, 21174–21187. [Google Scholar] [CrossRef] [PubMed]
  66. Ames, J.; Stringini Severo, E.; Guilherme da Costa-Silva, D.; Rosso Storck, T.; Blank do Amaral, A.M.; Azambuja Miragem, A.; Broock Rosemberg, D.; Loro, V.L. Glyphosate-based herbicide (GBH) causes damage in embryo-larval stages of zebrafish (Danio rerio). Neurotoxicol. Teratol. 2023, 95, 107147. [Google Scholar] [CrossRef]
  67. Liu, Y.; Guo, J.; Liu, W.; Yang, F.; Deng, Y.; Meng, Y.; Cheng, B.; Fu, J.; Zhang, J.; Liao, X.; Wei, L.; Lu, H. Effects of haloxyfop-p-methyl on the developmental toxicity, neurotoxicity, and immunotoxicity in zebrafish. Fish Shellfish Immunol. 2023, 132, 108466. [Google Scholar] [CrossRef]
  68. Hamed, H.S.; El-Sayed, Y.S. Antioxidant activities of Moringa oleifera leaf extract against pendimethalin-induced oxidative stress and genotoxicity in Nile tilapia, Oreochromis niloticus (L.). Fish Physiol. Biochem. A 2019, 45, 71–82. [Google Scholar] [CrossRef]
  69. Zhang, D.; Ding, W.; Liu, W.; Li, L.; Zhu. ; Ma J. Single and combined effects of chlorpyrifos and glyphosate on the brain of common carp: Based on biochemical and molecular perspective. Int. J. Mol. Sci. 2023, 24, 12934. [Google Scholar] [CrossRef]
  70. El-Nahhal, Y. Toxicity of some aquatic pollutants to fish. Environ. Monitor. Ass. 2018, 190, 449. [Google Scholar] [CrossRef]
  71. Viana, N.P.; Menezes da Silva, L.C.; Portruneli, N.; Soares, M.P.; Cardoso, I.L.; Bonansea, R.I.; Goulart, B.V.; Montagner, C.C.; Espíndola, E.L.G.; Wunderlin, D.A.; Fernandes, M.N. Bioconcentration and toxicological impacts of fipronil and 2,4-D commercial formulations (single and in mixture) in the tropical fish, Danio rerio. Environ. Sci. Pollut. Res. 2022, 29, 11685–11698. [Google Scholar] [CrossRef]
  72. Xiong, Y.; Wang, C.; Dong, M.; Li, M.; Hu, C.; Xu, X. Chlorphoxim induces neurotoxicity in zebrafish embryo through activation of oxidative stress. Environ. Toxicol. 2022, 38, 566–578. [Google Scholar] [CrossRef]
  73. Kavitha, P.; Rao, J.V. Toxic effects of chlorpyrifos on antioxidant enzymes and target enzyme acetylcholinesterase interaction in mosquito fish, Gambusia affinis. Environ. Toxicol. Pharmacol. 2008, 26, 192–198. [Google Scholar] [CrossRef] [PubMed]
  74. Topal, A.; Şişecioğlu, M.; Atamanalp, M.; Işık, A.; Yılmaz, B. The in vitro and in vivo effects of chlorpyrifos on acetylcholinesterase activity of rainbow trout brain. J. Appl. Anim. Res. 2016, 44, 243–247. [Google Scholar] [CrossRef]
  75. Oruç, E.Ö. Oxidative stress, steroid hormone concentrations and acetylcholinesterase activity in Oreochromis niloticus exposed to chlorpyrifos. Pest. Biochem. Physiol. 2010, 96, 160–166. [Google Scholar] [CrossRef]
  76. Touaylia, S.; Khazri, A.; Mezni, A.; Mezni, A. Assessment of biochemical biomarkers of mosquitofish (Gambusia affinis (Baird et Girard, 1853)) on exposure to the insecticide cypermethrin. Int. J. Environ. Stud. 2022. [Google Scholar] [CrossRef]
  77. Mishra, A.K.; Gopesh, A.; Singh, K.P. Effects of chlorpyrifos toxicity on brain, pseudobranchial neurosecretory system and swimming performance of a catfish, Heteropneustes fossilis. Drug Chem. Toxicol. 2023, 47, 67–80. [Google Scholar] [CrossRef]
  78. Pala, A.; Serdar, O.; Yonar, S.M.; Yonar, M.E. Ameliorative effect of Fennel (Foeniculum vulgare) essential oil on chlorpyrifos toxicity in Cyprinus carpio. Environ. Sci. Pollut. Res. 2021, 28, 890–897. [Google Scholar] [CrossRef]
  79. Silva de Souza, S.; Campos, D.F.; Machado, R.N.; Custodio da Costa, J.; Sebrenski da Silva, G.; Fonseca de Almeida-Val, V.M. Severe damages caused by Malathion exposure in Colossoma macropomum. Ecotoxicol. Environ. Saf. 2020, 205, 111340. [Google Scholar] [CrossRef]
  80. Chatterjee, A.; Bhattacharya, R.; Chatterjee, S.; Saha, N.C. λ cyhalothrin induced toxicity and potential attenuation of hematological, biochemical, enzymological and stress biomarkers in Cyprinus carpio L. at environmentally relevant concentrations: A multiple biomarker approach. Comp. Biochem. Physiol. C 2021, 250, 109164. [Google Scholar] [CrossRef]
  81. Zhang, W.; Fan, R.; Luo, S.; Liu, Y.; Jin, Y.; Li, Y.; Li, B.; Chen, Y.; Jia, L.; Yuan, X. Combined effects of chlorpyrifos and cyfluthrin on neurobehavior and neurotransmitter levels in larval zebrafish. J. Appl. Toxicol. 2022, 42, 1662–1670. [Google Scholar] [CrossRef]
  82. Weeks Santos, W.; Gonzalez, P.; Cormier, B.; Mazzella, N.; Moreira, A.; Clérandeau, C.; Morin, B.; Cachot, J. Subchronic exposure to environmental concentrations of chlorpyrifos affects swimming activity of rainbow trout larvae. Environ. Toxicol. Chem. 2021, 40, 3092–3102. [Google Scholar] [CrossRef]
  83. Mehtabidah, A.; Majid, M.; Hussain, I.; Kali, S.; Naz, T.; Niazi, M.B.K.; Khan, M.R.A.; Zafar, M.I. Chlorpyrifos mediated oxidative damage and histopathological alterations in freshwater fish Oncorhynchus mykiss in Northern Pakistan. Aquacult. Res. 2020, 51, 4583–4594. [Google Scholar] [CrossRef]
  84. Ran, L.; Yang, Y.; Zhou, X.; Jiang, X.; Hu, D.; Lu, P. The enantioselective toxicity and oxidative stress of dinotefuran on zebrafish (Danio rerio). Ecotoxicol. Environ. Saf. 2021, 226, 112809. [Google Scholar] [CrossRef] [PubMed]
  85. Guerra, L.J.; Blank do Amaral, A.M.; de Quadros, V.A.; da Luz Fiuza, T.; Rosemberg, D.B.; Prestes, O.D.; Zanella, R.; Clasen, B.; Loro, V.L. Biochemical and behavioral responses in zebrafish exposed to imidacloprid oxidative damage and antioxidant responses. Arch. Environ. Contam. Toxicol. 2021, 81, 255–264. [Google Scholar] [CrossRef] [PubMed]
  86. Zhang J-G. ; Ma D-D.; Xiong Q.; Qiu S-Q.; Huang G-Y.; Shi W-J.; Ying G.G. Imidacloprid and thiamethoxam affect synaptic transmission in zebrafish. Ecotoxicol. Environ. Saf. 2021, 227, 112917. [Google Scholar] [CrossRef] [PubMed]
  87. Rouachdia, R.; Trea, F.; Tichati, L.; Ouali, K. Assessment of biochemical markers and behavior response of non-target freshwater teleost Gambusia affinis to carbofuran toxicity. Appl. Ecol. Environ. Res. 2023, 21, 545–559. [Google Scholar] [CrossRef]
  88. Hamed, H.S.; Ismal, S.M.; Faggio, C. Effect of allicin on antioxidant defense system, and immune response after carbofuran exposure in Nile tilapia, Oreochromis niloticus. Comp. Biochem. Physiol. C 2021, 240, 108919. [Google Scholar] [CrossRef]
  89. Yu, T.; Xu, X.; Mao, H.; Han, X.; Liu, Y.; Zhang, H.; Lai, J.; Gu, J.; Xia, M.; Hu, C.; Li, D. Fenpropathrin exposure induces neurotoxicity in zebrafish embryos. Fish Physiol. Biochem. 2022, 48, 1539–1554. [Google Scholar] [CrossRef]
  90. Wang Y-J.; Chen C-Z.; Li P.; Liu L.; Chai Y.; Li Z-H. Chronic toxic effects of waterborne mercury on silver carp (Hypophthalmichthys molitrix) larvae. Water 2022, 14, 1774. [Google Scholar] [CrossRef]
  91. Mukherjee, D.; Saha, S.; Chukwuka, A.V.; Ghosh, B.; Dhara, K.; Saha, N.C.; Pal, P.; Faggio, C. Antioxidant enzyme activity and pathophysiological responses in the freshwater walking catfish, Clarias batrachus Linn under sub-chronic and chronic exposures to the neonicotinoid, Thiamethoxam®. Sci. Total Environ. 2022, 836, 155716. [Google Scholar] [CrossRef]
  92. Jablonski, C.A.; Brandão Pereira, T.C.; De Souza Teodoro, L.; Altenhofen, S.; Rübensam, G.; Bonan, C.D.; Bogo, M.R. Acute toxicity of methomyl commercial formulation induces morphological and behavioral changes in larval zebrafish (Danio rerio). Neurotoxicol. Teratol. 2022, 89, 107058. [Google Scholar] [CrossRef]
  93. Muhammed, M.; Dogan, D. Toxicity and biochemical responses induced by phosmet in rainbow trout (Oncorhynchus mykiss). Toxicol. Res. 2021, 10, 983–991. [Google Scholar] [CrossRef] [PubMed]
  94. Santillan Deiú, A.; de la Torre, F.R.; Ondarza, P.M.; Miglioranza, K.S.B. Multibiomarker responses and bioaccumulation of fipronil in Prochilodus lineatus exposed to spiked sediments: Oxidative stress and antioxidant defenses. Pest. Biochem. Physiol. 2021, 177, 104876. [Google Scholar] [CrossRef] [PubMed]
  95. Baldissera, M.D.; Souza, C.F.; Zanell, R.; Prestes, O.D.; Meinhart, A.D.; Da Silva, A.S.; Baldisserotto, B. Behavioral impairment and neurotoxic responses of silver catfish Rhamdia quelen exposed to organophosphate pesticide trichlorfon: Protective effects of diet containing rutin. Com. Biochem. Physiol. C 2021, 239, 108871. [Google Scholar] [CrossRef] [PubMed]
  96. Duncan, W.P.; Silva Idalino, J.J.; da SilvaA. G.; Moda R.F.; Menezes da Silva H.C.; Matoso D.A.; Silva Gomes A.L. Acute toxicity of the pesticide trichlorfon and inhibition of acetylcholinesterase in Colossoma macropomum (Characiformes: Serrasalmidae). Aquacult. Int. 2020, 28, 815–830. [Google Scholar] [CrossRef]
  97. Lu, J.; Zhang, M.; Lu, L. Tissue metabolism, hematotoxicity, and hepatotoxicity of trichlorfon in Carassius auratus gibelio after a single oral administration. Front. Physiol. 2018, 9, 551. [Google Scholar] [CrossRef]
  98. Flynn, K.; Johnson, R.; Lothenbach, D.; Swintek, J.; Whiteman, F.; Etterson, M. The effects of combinations of limited ration and diazinon exposure on acetylcholinesterase activity,growth and reproduction in Oryzias latipes, the Japanese medaka. J. Appl. Toxicol. 2020, 40, 535–547. [Google Scholar] [CrossRef]
  99. Singh, S.; Tiwari, R.K.; Pandey, R.S. Evaluation of acute toxicity of triazophos and deltamethrin and their inhibitory effect on AChE activity in Channa punctatus. Toxicol. Rep. 2018, 5, 85–89. [Google Scholar] [CrossRef]
  100. Rivero-Wendt, C.L.G.; Fernandes, L.G.; dos Santos, A.N.; Brito, I.L.; dos Santos Jaques, J.A.; dos Santos dos Anjos, E.; Fernandes, C.E. Effects of Chloramine T on zebrafish embryos malformations associated with cardiotoxicity and neurotoxicity. J. Toxicol. Environ. Health A 2023, 86, 372–381. [Google Scholar] [CrossRef]
  101. Chen, Y.; Liu, C.; Xiao, L.; Gao, G.; He, L.; Zhao, K.; Shang, X. 2, 5-dichloro-1, 4-benuinone exposure to zebrafish embryos/larvae causes neurodevelopmental toxicity. Ecotoxicol. Environ. Saf. 2022, 243, 114007. [Google Scholar] [CrossRef]
  102. Orozco-Hernández, J.M.; Gómez-Oliván, L.M.; Elizalde-Velázquez, G.A.; Rosales-Pérez, K.E.; Cardoso-Vera, J.D.; Heredia-García, G.; Islas-Flores, H.; García-Medina, S.; Galar-Martínez, M. Fluoxetine-induced neurotoxicity at environmentally relevant concentrations in adult zebrafish Danio rerio. Neurotoxicol. 2022, 90, 121–129. [Google Scholar] [CrossRef]
  103. Correia, D.; Domingues, I.; Faria, M.; Oliveira, M. Chronic effects of fluoxetine on Danio rerio: A biochemical and behavioral perspective. Appl. Sci. 2022, 12, 2256. [Google Scholar] [CrossRef]
  104. Deepika, D.; Padmavathy, P.; Srinivasan, A.; Sugumar, G.; Jawahar, P. Short term effects of antimicrobial agent triclosan on Oreochromis mossambicus (Peters, 1852): Biochemical and genetic alterations. Ind. J. Anim. Res. 2023, 57, 788–794. [Google Scholar] [CrossRef]
  105. Sager, E.; Scarcia, P.; Marino, D.; Mac Loughlin, T.; Rossi, A.; de La Torre, F. Oxidative stress responses after exposure to triclosan sublethal concentrations: An integrated biomarker approach with a native (Corydoras paleatus) and a model fish species (Danio rerio). J. Toxicol. Environ. Health A 2022, 85, 291–306. [Google Scholar] [CrossRef] [PubMed]
  106. Tan, Y.; Liang, C.; Guo, Y.; Zou, H.; Guo, Y.; Ye, J.; Hou, L.; Wang, X. Thyroid endocrine disruption and neurotoxicity of gestodene in adult female mosquitofish (Gambusia affinis). Chemosphere, 2023, 313, 37594. [Google Scholar] [CrossRef] [PubMed]
  107. Rocha, C.S.; Puchale, R.Z.; Barcarolli, I.F. Avaliação toxicológica da progesterona em biomarcadores de tilápia do Nilo (Oreochromis niloticus). Rev. Bras. Meio Amb. 2022, 10, 26–40. [Google Scholar]
  108. Elizalde-Velázquez, G.A.; Gómez-Oliván, L.M.; García-Medina, S.; Rosales-Pérez, K.E.; Orozco-Hernández, J.M.; Islas-Flores, H.; Galar-Martínez, M.; Hernández-Navarro, M.D. Chronic exposure to realistic concentrations of metformin prompts a neurotoxic response in Danio rerio adults. Sci. Total Environ. 2022, 849, 157888. [Google Scholar] [CrossRef]
  109. Yang, H.; Gu, X.; Chen, H.; Zeng, Q.; Mao, Z.; Jin, M.; Li, H.; Ge, Y.; Zha, Y.; Martyniuk, C.J. Transcriptome profiling reveals toxicity mechanisms following sertraline exposure in the brain of juvenile zebrafish (Danio rerio). Ecotoxicol. Environ. Saf. 2022, 242, 113936. [Google Scholar] [CrossRef]
  110. Oliveira, A.C.; Fascineli, M.L.; Andrade, T.S.; Sousa-Moura, D.; Domingues, I.; Camargo, N.S.; Oliveira, R.; Grisolia, C.K.; Villacis, R.A.R. Exposure to tricyclic antidepressant nortriptyline affects early-life stages of zebrafish (Danio rerio). Ecotoxicol. Environ. Saf. 2021, 210, 111868. [Google Scholar] [CrossRef]
  111. Muniz, M.S.; Halbach, K.; Araruna, I.C.A.; Martins, R.X.; Seiwert, B.; Lechtenfeld, O.; Reemtsma, T.; Farias, D. Moxidectin toxicity to zebrafish embryos: Bioaccumulation and biomarker responses. Environ. Pollut. 2021, 283, 117096. [Google Scholar] [CrossRef]
  112. Li, P.; Li Z-H. Neurotoxicity and physiological stress in brain of zebrafish chronically exposed to tributyltin. J. Toxicol. Environ. Health A 2021, 84, 20–30. [Google Scholar] [CrossRef]
  113. Murugan, R.; Arokiyaraj, B.H.S.; Arockiaraj, J. Deacetyl epoxyazadiradione ameliorates BPA-induced neurotoxicity by mitigating ROS and inflammatory markers in N9 cells and zebrafish larvae. Comp. Biochem. Physiol. C 2023, 271, 109692. [Google Scholar] [CrossRef] [PubMed]
  114. Rao, J.V.; Begum, G.; Pallela, R.; Usman, P.K.; Rao, R.N. Changes in behavior and brain acetylcholinesterase activity in mosquito fish, Gambusia affinis in response to the sub-lethal exposure to chlorpyrifos. Int. J. Environ. Res. Pub. Health 2023, 2, 478–483. [Google Scholar] [CrossRef] [PubMed]
  115. Belhamra, R.; Tichati, L.; Trea, F.; Ouali, K. Effect of subacute treatment with bisphenol A on oxidative stress biomarkers and lipid peroxidation in Gambusia affinis mosquitofish. Toxicol. Environ. Health Sci. 2023, 15, 61–72. [Google Scholar] [CrossRef]
  116. Lin, H.; Jia, Y.; Han, F.; Xia, C.; Zhao, Q.; Zhang, J.; Li, E. Toxic effects of waterborne benzylparaben on the growth, antioxidant capacity and lipid metabolism of Nile tilapia (Oreochromis niloticus). Aquat. Toxicol. 2022, 248, 106197. [Google Scholar] [CrossRef] [PubMed]
  117. Raja, G.L.; Subhashree, K.D.; Lite, C.; Santosh, W.; Barathi, S. Transient exposure of methylparaben to zebrafish (Danio rerio) embryos altered cortisol level, acetylcholinesterase activity and induced anxiety-like behaviour. Gen. Comp. Endocrinol. 2019, 279, 53–59. [Google Scholar] [CrossRef]
  118. Thakkar, S.; Seetharaman, B.; Ramasamy, V. Impact of chronic sub-lethal methylparaben exposure on cardiac hypoxia and alterations in neuroendocrine factors in zebrafish model. Mol. Biol. Rep. 2022, 49, 331–340. [Google Scholar] [CrossRef]
  119. Gayathri, M.; Sutha, J.; Mohanthi, S.; Ramesh, M.; Poopal R-K. Ecotoxicological evaluation of the UV-filter octocrylene (OC) in embryonic zebrafish (Danio rerio): Developmental, biochemical and cellular biomarkers. Comp. Biochem. Physiol. C 2023, 271, 109688. [Google Scholar] [CrossRef]
  120. Pérez-Iglesias, J.M.; González, P.; Calderón, M.R.; Natale, G.S.; Almeida, C.S. Comprehensive evaluation of the toxicity of the flame retardant (decabromodiphenyl ether) in a bioindicator fish (Gambusia affinis). Environ. Sci. Pollut. Res. 2022, 29, 50845–50855. [Google Scholar] [CrossRef]
  121. Sandoval-Gío, J.J.; Noreña-Barroso, E.; Escalante-Herrera, K.; Rodríguez-Fuentes, G. Effect of benzophenone-3 to acetylcholinesterase and antioxidant system in zebrafish (Danio rerio) embryos. Bull. Environ. Contam. Toxicol. 2021, 107, 814–819. [Google Scholar] [CrossRef]
  122. Chen, X.; Guo, W.; Lei, L.; Guo, Y.; Yang, L.; Han, J.; Zhou, B. Bioconcentration and developmental neurotoxicity of novel brominated flame retardants, hexabromobenzene and pentabromobenzene in zebrafish. Environ. Pollut. 2021, 268, 115895. [Google Scholar] [CrossRef]
  123. Sayed, A. L-D.H.; Soliman H.A.M.; Idriss S.K.; Abdel-Ghaffar S.K.; Hussein A.A.A. Oxidative stress and immunopathological alterations of Clarias gariepinus exposed to monocyclic aromatic hydrocarbons (BTX). Water Air Soil Pollut. 2023, 234, 354. [Google Scholar] [CrossRef]
  124. Molayemraftar, T.; Peyghan, R.; Jalali, M.R.; Shahriari, A. Single and combined effects of ammonia and nitrite on common carp, Cyprinus carpio: Toxicity, hematological parameters, antioxidant defenses, acetylcholinesterase, and acid phosphatase activities. Aquaculture 2022, 548, 737676. [Google Scholar] [CrossRef]
  125. Mariz, C.F.; de Melo Alves, M.K.; Ventura Dos Santos, S.M.; Alves, R.N.; Carvalho, P.S.M. Lethal and sublethal toxicity of un-ionized ammonia to early life stages of Danio rerio. Zebrafish 2023, 20, 67–76. [Google Scholar] [CrossRef] [PubMed]
  126. Gopi, N.; Iswarya, A.; Vijayakumar, S.; Jayanthi, S.; Nord, A.S.M.; Velusamye, P.; Vaseeharan, B. Protective effects of dietary supplementation of probiotic Bacillus licheniformis Dahb1 against ammonia induced immunotoxicity and oxidative stress in Oreochromis mossambicus. Comp. Biochem. Physiol. C 2022, 259, 109379. [Google Scholar] [CrossRef]
  127. Passos, L.S.; Gomes, L.C.; Pereira, T.M.; Sadauskas-Henrique, H.; Dal Pont, G.; Ostrensky, A.; Pinto, E. Response of Oreochromis niloticus (Teleostei: Cichlidae) exposed to a guanitoxin-producing cyanobacterial strain using multiple biomarkers. Sci. Total Environ. 2022, 835, 155471. [Google Scholar] [CrossRef]
  128. Nirmala, G.N.; Sharma, A.; Ragunathan, V. Antagonistic effect of dichloromethane on Oreochromis mossambicus and immune stimulation activity of Aloe vera. Front. Environ. Sci. 2022, 10, 913065. [Google Scholar] [CrossRef]
  129. Muthukumaravel, K.; Vasanthi, N.; Kanagavalli, V.; Santhanabharathi, B.; Pradhoshini, K.P.; Alam, L.; Faggio, C. Potential biomarker of phenol toxicity in freshwater fish C. mrigala: Serum cortisol, enzyme acetylcholine esterase and survival organ gill. Comp. Biochem. Physiol. C 2023, 263, 109492. [Google Scholar] [CrossRef]
  130. Iheanacho, S.C.; Ekpenyong, J.; Nwose, R.; Adeolu, A.I.; Offu, P.; Amadi-Eke, A.; Iheanacho, A.C.; Ogunji, J. Effects of burnt tire-ash on Na+/K+, Ca2+-ATPase, serum immunoglobulin and brain acetylcholinesterase activities in Clarias gariepinus (Burchell, 1822). Drug Chem. Toxicol. 2023, 46, 503–509. [Google Scholar] [CrossRef]
  131. Schmitt, C.; Peterson, E.; Willis, A.; Kumar, N.; McManus, M.; Subbiah, S.; Crago, J. Transgenerational effects of developmental exposure to chlorpyrifos-oxon in zebrafish (Danio rerio). Toxicol. Appl. Pharmacol. 2020, 408, 115275. [Google Scholar] [CrossRef]
  132. Brander, S.M.; White, J.W.; DeCourten, B.M.; Major, K.; Hutton, S.J.; Connon, R.E.; Mehinto, A. Accounting for transgenerational effects of toxicant exposure in population models alters the predicted long-term population status. Environ. Epigen. 2022, 8, 1–12. [Google Scholar] [CrossRef]
  133. Issac, P.K.; Guru, A.; Velayutham, M.; Pachaiappan, R.; Arasu, M.V.; Al-Dhabi, N.A.; Choi, K.C.; Harikrishnan, R.; Arockiaraj, J. Oxidative stress induced antioxidant and neurotoxicity demonstrated in vivo zebrafish embryo or larval model and their normalization due to morin showing therapeutic implications. Life Sci. 2021, 283, 119864. [Google Scholar] [CrossRef] [PubMed]
  134. Jha, R.; Rizvi, S.I. Age-dependent decline in erythrocyte acetylcholinesterase activity: Correlation with oxidative stress. Biomed. Pap. Med. Faculty University Palacky Olomouc Czech Republic 2009, 153, 195–198. [Google Scholar] [CrossRef] [PubMed]
  135. Liu, H.; Wu, J.; Yao J-Y. ; Wang H.; Li S-T. The role of oxidative stress in decreased acetylcholinesterase activity at the neuromuscular junction of the diaphragm during sepsis. Oxidat. Med. Cell. Longevity 2017, 9718615. [Google Scholar] [CrossRef] [PubMed]
  136. Melo, J.B.; Agostinho, P.; Oliveira, C.R. Involvement of oxidative stress in the enhancement of acetylcholinesterase activity induced by amyloid beta-peptide. Neurosci. Res. 2003, 45, 117–127. [Google Scholar] [CrossRef]
  137. Nájera-Martínez, M.; Landon-Hernández, G.G.; Romero-López, J.P.; Domínguez-López, M.L.; Vega-López, A. Disruption of neurotransmission, membrane potential, and mitochondrial calcium in the brain and spinal cord of Nile tilapia elicited by Microcystis aeruginosa extract: An uncommon consequence of the eutrophication process. Water Air Soil Pollut. 2022, 233, 6. [Google Scholar] [CrossRef]
  138. Santana, M.S.; Sandrini-Neto, L.; Di Domenico, M.; Mela Prodocimo, M. Pesticide effects on fish cholinesterase variability and mean activity: A meta-analytic review. Sci. Total Environ. 2021, 757, 143829. [Google Scholar] [CrossRef]
  139. Ortiz-Delgado, J.B.; Funes, V.; Albendín, G.; Scala, E.; Sarasquete, C. Toxicity of malathion during Senegalese sole, Solea senegalensis larval development and metamorphosis: Histopathological disorders and effects on type B esterases and CYP1A enzymatic systems. Environ. Toxicol. 2021, 36, 1894–1910. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.
Prerpints.org logo

Preprints.org is a free preprint server supported by MDPI in Basel, Switzerland.

facebook logotwitter logolinkedin logo
bsky
MDPI Initiatives
Important Links
Subscribe

Disclaimer

Terms of Use

Privacy Policy

Privacy Settings

© 2025 MDPI (Basel, Switzerland) unless otherwise stated