Role of Gal-3 mediated lysophagy in arsenic-induced chicken hepatocyte injury

Arsenic is one of the important pollutants in the environment. As the main target organ of arsenic exposure, the liver contains a large number of lysosomes, which play an important role in liver injury induced by arsenic. The involvement of lysosomes in arsenic-induced hepatic damage among avian species, specifically chickens, has yet to be documented. Therefore, in this study, we established animal models of chickens and primary chicken hepatocyte models with different concentrations of arsenic trioxide (ATO) and further explored the hepatotoxic mechanism of arsenic from the perspective of lysosome damage. Our study confirmed that ATO affected the growth and development of chickens; caused substantial liver damage with decreased antioxidant capacity. Our study also found that exposure to ATO leads to lysosomal damage. This leads to the leakage of tissue protease B (CTSB) within lysosomes and triggers the Gal-3-dependent lysosomal phagocytosis mechanism to eliminate the damaged lysosomes.Moreover, we also found that lysosome damage and lysophagy induced by ATO were associated with intracellular Ca 2+ disturbance. Taken together, the results show that ATO can induce lysosome damage and activate Gal-3 mediated lysophagy. • Liver injury was induced in chickens exposed to arsenic trioxide (ATO). • ATO induced lysophagy in both ex vivo and in vivo models of chicken liver. • The use of si-Gal-3 effectively attenuates ATO-induced lysophagy in chicken hepatocytes.