Role of autophagy and apoptosis in aluminum exposure-induced liver injury in rats

Abstract

Aluminum exposure can lead to different degrees of damage to various organ systems of the body. It has been previously revealed that that aluminum exposure can damage the liver, causing liver dysfunction. However, the specific mechanism remains unclear. This research aims to uncover the damaging effect of aluminum exposure on rat liver and to demonstrate the role of autophagy and apoptosis in this effect. Thirty-two Wistar rats were randomly divided into the control group (C group), low-dose aluminum exposure group (L group), middle-dose aluminum exposure group (M group), and high-dose aluminum exposure group (H group) (n = 8). The rats respectively received intraperitoneal injection of 0, 5, 10 and 20 mg/(kg·d) AlCl3 solution for 4 w (5 times/w). After the experiment, changes in the ultrastructure and autolysosome in rat liver were observed; the liver function, apoptosis rate, as well as levels of apoptosis-associated proteins and autophagy-associated proteins were detected. The results indicated that aluminum exposure damaged rat liver function and structure and resulted in an increase of autolysosomes. TUNEL staining revealed an elevated number of apoptotic hepatocytes after aluminum exposure. Moreover, we found from Western blotting that the levels of autophagy-associated proteins Beclin1 and LC3-II increased; apoptotic protein Caspase-3 level elevated and Bcl-2/Bax ratio reduced. Our research suggested that aluminum exposure can lead to high autophagy and apoptosis levels of rat hepatocytes, accompanied by hepatocyte injury and impaired liver function. This study shows that autophagy and apoptosis pathways participate in aluminum toxication-induced hepatocyte injury.