Inorganic mercury induces liver oxidative stress injury in quails by inhibiting Akt/Nrf2 signal pathway

Abstract

Mercury is widely used in human life and production. Excessive mercury can accumulate in livestock and poultry through air, drinking water, and food, which causes a serious threat to natural environment and human food safety. However, the exact mechanism of hepatotoxicity caused by mercuric chloride (HgCl2) is still unclear. The purpose of this study is to explore the mechanism of HgCl2 poisoning in the liver. Based on the above background, 28 quails were randomly and equally divided into 4 groups to establish a hepatotoxicity model by oral administration of HgCl2 once daily (0 mg/kg, 2 mg/kg, 4 mg/kg, and 8 mg/kg, respectively). The experiment period was 84 d. The assay results of blood routine and biochemical indexes showed liver injury in quails. Further research found that mRNA and protein levels of nuclear factor-erythroid related factor 2 (Nrf2) and its key promoter protein kinase B (Akt) were significantly decreased, suggesting HgCl2 treatment led to liver oxidative stress injury in a dose-dependent manner by inhibiting the antioxidant signal pathway Akt/Nrf2. Besides, the increase of nuclear factor-κB and tumor necrosis factor-alpha levels as well as the activation of tumor protein 53 indicated the occurrence of inflammation and apoptosis. Moreover, the inhibition of multidrug resistance protein 2 (Mrp2) which participates in HgCl2-mediated toxicant metabolism resulted in toxicity accumulation. Thus, a vicious circle was formed to further aggravate the liver injury. In conclusion, our results demonstrated that HgCl2 leads to liver inflammation, apoptosis, and detoxification dysfunction by inhibiting the antioxidant pathway Akt/Nrf2. Among them, Akt and Mrp2 may be effective therapeutic targets for the treatment of HgCl2-triggered hepatotoxicity.