Study on the mechanism underlying Al-induced hepatotoxicity based on the identification of the Al-binding proteins in liver

Abstract

Aluminum (Al) is the most abundant metal element in the earth's crust, and is implicated in the pathogenesis of liver lesions. However, the mechanisms underlying Al³⁺-induced hepatotoxicity are still largely elusive. Based on analysis with native gel electrophoresis, Al³⁺ plus 8-hydroxyquinoline staining and LC-MS/MS, the proteins with high Al³⁺ affinity were identified to be carbamoyl-phosphate synthase, adenosylhomocysteinase, heat shock protein 90-alpha, carbonic anhydrase 3, serum albumin and calreticulin. These proteins are involved in physiological processes such as the urea cycle, redox reactions, apoptosis and so on. Then we established an Al³⁺-treated rat model for biochemical tests, morphology observation and Ca²⁺ homeostasis analysis, in order to evaluate the extent of oxidative damage, hepatic histopathology and specific indicators of Al³⁺-related proteins in liver. Our findings indicated the high-affinity interactions with Al³⁺ perturbed the normal function of the above proteins, which could account for the mechanism underlying Al³⁺-induced hepatotoxicity.