The pathogenesis of Degnala disease involves a complex interplay between the ingested mycotoxins, the immune response of the affected animal, and environmental factors. The primary pathological changes occur in the skin and subcutaneous tissues of the extremities, although systemic effects can also be observed
. Degnala is a mycotoxicosis caused by toxins produced by toxigenic fungi, and the fungus
Fusarium spp. is the main causative agent [
9,
15,
16]. The disease was reproduced experimentally, and three species of the genus
Fusarium were identified in the rice straw supplied to buffaloes, namely,
F. oxysporum, F. equiseti, and
F. moniliforme. The animals developed the disease only when
F. oxysporum was present [
12]. Other fungi, such as
Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Penicillium spp. and
Fusarium spp., which are fungal species with variable toxigenic capacities (especially
Fusarium spp., which produce toxins with greater cytotoxic effects), are frequently found in rice straw supplied to buffaloes [
13,
14]. Buffaloes ingest mycotoxin-contaminated fodder, which leads to the absorption of these toxins through the gastrointestinal tract. The toxins enter the bloodstream and are distributed throughout the body, reaching the peripheral tissues. Mycotoxins exert direct cytotoxic effects on the cells of the skin and subcutaneous tissues, leading to cell death and tissue necrosis. These toxins inhibit protein synthesis and disrupt cellular membranes, causing cell lysis and inflammatory responses. The immune system responds to the damaged tissues and the presence of toxins, resulting in inflammation. Inflammatory mediators are released, further exacerbating tissue damage and leading to the clinical signs of dermatitis and necrosis [
9,
15,
16].The toxins ochratoxin A, zearalenone and citrinin are commonly isolated from straws of different grains containing the fungi
Fusarium spp.,
Aspergillus spp. and
Penicillium spp. [
13]. The main toxin involved in the pathogenesis of Degnala disease is the T-2 toxin, which is typically produced by different strains of the fungus
Fusarium spp. [
17,
18] and is considered one of the most potent toxins of Group A [
19]. Another group of studies identified aflatoxins B1 and B2 in rice straw containing the fungi
Fusarium spp.,
Aspergillus spp. and
Penicillium spp. [
14]. Degnala disease in buffaloes is primarily caused by the ingestion of aflatoxins, particularly aflatoxin B1, which is produced by the fungus Aspergillus flavus. Aflatoxins are potent carcinogenic mycotoxins that can contaminate a variety of agricultural commodities, including grains, nuts, and oilseeds, under conditions of high temperature and humidity. Buffaloes are particularly susceptible to aflatoxin ingestion due to their dietary habits and digestive physiology. Once ingested, aflatoxin B1 is metabolized in the liver by cytochrome P450 enzymes to form a reactive intermediate, aflatoxin B1-8,9-epoxide. This epoxide is highly reactive and can bind to cellular macromolecules, including DNA, proteins, and lipids, leading to cellular damage and dysfunction. In the case of Degnala disease, the liver is the primary target organ for aflatoxin toxicity. The liver plays a crucial role in the metabolism and detoxification of aflatoxins. However, prolonged exposure to high levels of aflatoxins can overwhelm the liver's detoxification mechanisms, leading to the accumulation of toxic metabolites and subsequent liver damage. Aflatoxin-induced liver damage can manifest as hepatocellular necrosis, fibrosis, and cirrhosis, impairing the liver's function and overall health of the animal. In addition to liver damage, aflatoxins can also affect the reproductive system in buffaloes. Aflatoxin B1 and its metabolites can cross the placental barrier and accumulate in reproductive tissues, including the ovaries and uterus, leading to reproductive disorders. Aflatoxin exposure in pregnant buffaloes can result in embryonic death, abortion, and the birth of weak or stillborn calves. Furthermore, aflatoxins can have immunosuppressive effects, making buffaloes more susceptible to infections and other diseases. This immunosuppression can further exacerbate the health problems associated with Degnala disease and increase the risk of secondary infections [
13,
14]. However, no scientific studies have evaluated the toxins present in animals.
The occurrence of Degnala disease is closely associated with the presence of aflatoxin-contaminated feedstuffs, particularly grains, oilseeds, and crop residues. Aflatoxins are produced by the fungus Aspergillus flavus, which can contaminate feedstuffs during cultivation, harvesting, storage, and processing. Factors such as high temperature, high humidity, improper storage conditions, and insect damage can promote aflatoxin contamination in feedstuffs. Buffaloes of all ages and sexes are susceptible to Degnala disease, but it is more commonly observed in adult female buffaloes, particularly those in the reproductive age group. Pregnant buffaloes are especially vulnerable to the effects of aflatoxin toxicity, as it can lead to reproductive disorders such as abortion, stillbirth, and neonatal mortality. The occurrence of Degnala disease can vary seasonally, with higher incidences reported during periods of high temperature and humidity, which favor fungal growth and aflatoxin production. Additionally, outbreaks of Degnala disease are often associated with the consumption of contaminated feedstuffs, particularly during times of feed scarcity or poor feed management practices. The economic impact of Degnala disease is significant, as it can lead to reduced milk production, reproductive failure, increased veterinary costs, and losses due to calf mortality. Furthermore, aflatoxin-contaminated milk from affected buffaloes can pose a health risk to consumers, as aflatoxins are carcinogenic and can accumulate in milk and dairy products. In conclusion, Degnala disease is a major health concern for buffaloes in regions where aflatoxin contamination in feedstuffs is prevalent. Understanding the occurrence and risk factors associated with Degnala disease is essential for implementing effective preventive and control measures to minimize its impact on buffalo populations and the dairy industry [
9,
14,
15].
Another possible explanation is that Degnala disease can be caused by selenium poisoning due to the contamination of rice straw in selenium-rich soil [
20,
21]. However, this hypothesis has been ruled out by the reproduction of the disease in buffaloes fed rice straw contaminated with
F. oxysporum and the presence of serum selenium levels within the normal range for the species [
12]. In addition, selenium accumulation occurs in more arid areas, and the period in which there is an accumulation of selenium in the soil does not coincide with the seasonality of the disease [
13].
The pathogenesis of clinical gangrene syndrome is unknown[
15]; however, there are several findings, hypotheses and suggestions associated with the process. Initially, the ingestion of rice straw infested by fungi occurs, which leads to the release of toxins in the intestine. Toxins are absorbed and reach the liver through the circulatory system and later reach peripheral tissues, where they cause vasoconstriction in the extremities, which leads to obstruction of the blood supply, causing anoxia and tissue necrosis [
17,
22,
23]. It has also been reported that the dissolution of collagen and elastin leads to the appearance of skin lesions, which occur concomitantly with an increase in the thickness of blood vessels and the presence of thrombi and eosinophilic infiltration [
24].