Zinc Alleviates Acetaminophen-aggravated Hepatic Steatosis

Purpose:Abnormal accumulation of lipid droplets in hepatocytes is a symbolic event of hepatic steatosis and a pathological feature of metabolic syndrome related to liver diseases（nonalcoholic fatty liver,alcoholic fatty liver,etc.）.The abnormal accumulation of lipid droplets is caused by the imbalance of dynamic changes（formation and degradation）of lipid droplets.Autophagy is a very important way to degrade lipid droplets,and the inhibition of autophagy will inhibit the degradation of lipid droplets,which will lead to hepatic steatosis.In this paper,acetaminophen（APAP）,a common inducer of drug-induced liver injury,was used as a model to explore the role of autophagy disorder in aggravating hepatocyte steatosis,and further explore the inhibitory effect of trace element zinc.Method:（1）The effect of APAP on hepatocyte steatosis was detected by the number and composition of lipid droplets.（2）The autophagy changes in hepatocyte steatosis aggravated by APAP were detected by dansyl cadaverine,lysosomal tracer and acridine orange,and several different autophagy inhibitors were used to verify them.H₂DCFDA and ethidium dihydrochloride were used to detect the oxidative stress of hepatocyte steatosis aggravated by APAP.（3）By using zinc chelating agent and zinc carrier to change the content of zinc in cells,the positive and negative effects of zinc on alleviating APAP-aggravated hepatocyte steatosis were verified.Results:（1）APAP-aggravated hepatocyte steatosis,which was manifested by the increase of lipid droplets and the increase of triglyceride and total cholesterol levels;（2）APAP leads to autophagy damage and lysosomal function decline,which may be the reason why it aggravates hepatic steatosis;（3）Using autophagy inhibitor to aggravate autophagy damage caused by APAP can further aggravate fatty degeneration of hepatocytes;（4）Zinc can improve the fatty degeneration of hepatocytes aggravated by APAP by regulating autophagy and exerting antioxidant effect.Conclusion:APAP aggravated the steatosis of hepatocytes by inhibiting autophagy,and zinc can maintain the normal operation of autophagy and play an antioxidant role,thus improving the steatosis of hepatocytes aggravated by APAP.