Abstract
Arsenic is a well-known environmental toxicant and carcinogen, which has been epidemiologically proved related to the increased hepatic disorders. Researches have shown that aseptic inflammation and abnormal immune response are associated with arsenic-induced liver injury. However, the immunotoxic effects of liver have not been extensively characterized. Ginkgo biloba extract (GBE), a natural products of G. biloba leaves with proven anti-inflammatory and potential immunoregulatory activities, was used as intervention agent to explore its protective effects on arsenic-induced hepatotoxicity. Thus, the underlying mechanism of the immunotoxic effects on arsenic-induced liver injury were investigated in 2.5, 5.0, and 10.0 mg/kg NaAsO2 of Wistar rats for 16 weeks. Subsequently, GBE was used as intervention agent in 50 mg/kg for 6 weeks after cessation of arsenic exposure. The ratio of Th17 to Treg cells in peripheral blood as well as the secretion of inflammatory cytokines IL-17A, IL-6, TGF-β1, and IL-10 in serum and liver were detected. Meanwhile, the notable activation of aseptic inflammation-related molecule TLR4 and its downstream targets MyD88 and NF-κB in the liver were observed. In this work, we confirmed that subchronic exposed to arsenic triggered the infiltration of inflammatory cells in rat liver, coupled with obvious histopathological changes and aberrant hepatic serum biochemical parameters. Meanwhile, imbalanced immune response was verified by the notable abnormal ratio of Th17 to Treg cells in peripheral blood as well as the secretion of inflammatory cytokines IL-17A, IL-6, TGF-β1, and IL-10 in serum and liver of arsenic exposed rats. Further, the level of TLR4, MyD88, and NF-κB in liver both transcription and translation activity were raised. Subsequently, GBE markedly mitigated arsenic-induced liver injury, most impressively, post treatment with GBE prominently suppressed the overactivated inflammatory-related TLR4-MyD88-NF-κB pathway and evidently decreased the secretion of inflammation cytokines. Meanwhile, the disturbance of pro- and anti-inflammatory response was reversed. We concluded that the disruption of pro- and anti-inflammatory T-cells balance caused by cytokines mediated cell-cell interactions may be one of the mechanisms underlying arsenic-induced liver injury and that GBE intervention exerts an evidence protective effects, which might be closely associated with the suppression of inflammatory-related TLR4 pathway.