Abstract
The fungal metabolites produced by Aspergillus flavus and Aspergillus parasiticus cause detrimental health effects on humans and animals. Particularly aflatoxin B1 (AFB1) is the most studied and a well-known global carcinogen, producing hepatotoxic, genotoxic and immunotoxic effects in multiple species. AFB1 is shown to provoke liver dysfunctioning by causing hepatocytes apoptosis and disturbing cellular enzymatic activities. In liver, AFB1 causes apoptosis via extrinsic mechanism because of high expression of death receptor pathway. The detailed mechanism of AFB1 induced hepatocytes apoptosis, via death receptor pathway still remains elusive. So the present study was conducted to explore apoptotic mechanism initiated by death receptors and associated genes in aflatoxin B1 induced liver apoptosis in chickens fed with AFB1 for 3 weeks. Results from the present study displayed histopathological and ultrastructural changes in liver such as hydropic degeneration, fatty vacuolar degeneration and proliferation of bile duct in hepatocytes in AFB1 group, along with imbalance between reactive oxygen species (ROS) and antioxidant defense system upon AFB1 ingestion. Moreover, AFB1 intoxicated chickens showed upregulation of death receptors FAS, TNFR1 and associated genes and downregulation of inhibitory apoptotic proteins XIAP and BCL-2. The results obtained from this novel and comprehensive study including histopathological, ultrastructural, flow cytometrical and death receptor pathway gene expression profiles, will facilitate better understanding of mechanisms and involvement of death receptor pathway in hepatocytes apoptosis induced by AFB1 and ultimately may be helpful in bringing down the toxigenic potential of AFB1.
Highlights
Aflatoxins are probably the most intensively researched mycotoxins in the world as 4.5 billion people worldwide suffer from intemperate exposure to aflatoxins which causes 4.6–28.2% of all global hepatocellular carcinoma cases [1, 2]
The present study was conducted to explore apoptotic mechanism initiated by death receptors and associated genes in aflatoxin B1 induced liver apoptosis in chickens fed with AFB1 for 3 weeks
The present study revealed over expression of Fatty acid synthetase receptor (FAS) and TNF-Tumor necrosis factor receptor 1 (R1) receptors along with their associated genes i-e cysteineaspartic protease (CASPASE) 8, CASPASE 10, FAS-associated death domain (FADD), TRADD and TNF receptor-associated factor 2 (TRAF2), which was consistent with earlier reports in human hepatocytes [38, 39] and with our recent study on thymocytes apoptosis [23]
Summary
Aflatoxins are probably the most intensively researched mycotoxins in the world as 4.5 billion people worldwide suffer from intemperate exposure to aflatoxins which causes 4.6–28.2% of all global hepatocellular carcinoma cases [1, 2]. These fungal metabolites are mainly produced by Aspergillus flavus and Aspergillus parasiticus. Aflatoxin B1 (AFB1) is the most widely known carcinogen [5] having highly hepatotoxic, genotoxic, immunotoxic, and other adverse health effects on humans and several other animal species [6]. AFB1 are hepatotoxic, causing pallor discoloration, enlargement, congestion and necrosis of liver along with triggering proliferation of bile duct and infiltration of mononuclear and heterophilic cells in many livestock and laboratory animals, yet susceptibility varies with breed, species, age, dose, length of exposure and nutritional status [13,14,15]
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