Nickel-induced Liver Injury And Protective Effects Of Grape Seed Procyanidin Extract In Male Rats

Objective:To investigate the adverse effects of nickel sulfate (NiSO4) and its mechanism on liver cells and the protective effects of grape seed procyanidin extract (GSPE) from the perspective of oxidative stress and apoptosis in male rats. Methods:(1) Study on adverse effects of nickel sulfate and its mechanism in rat liver cells.32 health male Wistar rats were divided into four groups including three NiSO4 exposure groups and control group. The exposure groups administrated intraperitoneally with NiSO4 at doses of 1.25,2.50 and 5.00mg/kg once a day for 30 days respectively, and control group was treated with normal saline by same condition. Rats were sacrificed by dislocation of cervical vertebra to weigh livers and evaluate organ coefficient. The activities of superoxide dismutase (SOD), glutathion peroxidase (GSH-Px), catalase (CAT), and the contents of Total-antioxidative capability (T-AOC), malondialdehyde (MDA) and hydrogen peroxide (H2O2) were measured by spectrophotometry assay. The protein expression levels of Bax, Bcl-2 and Caspase-3 in rat liver cells were detected with Western blot technique. (2) Protective effects of GSPE against nickel sulfate induced liver injury in male rats.40 health male Wistar rats with sexual maturation were divided into five groups randomly, including control group with normal saline solution, the model group administrated intraperitoneally with NiSO4 at dose of 2.50mg/kg and normal saline treated with intragastric administration, and the intervention groups administrated with 2.50mg/kg NiSO4 by intraperitoneal injection and GSPE at doses of 50,100 and 200mg/kg by intragastric administration once a day for 30 days respectivelly. All experimental methods were same as the first part. Results:(1) Compared with control group, the organ coefficient decreased in NiSO4 2.50mg/kg and 5.00mg/kg groups (P<0.05). The activities of GSH-Px and CAT were inhibited by nickel sulfate at doses of 2.50 and 5.00mg/kg, but SOD and T-AOC inhibited only in NiSO4 5.00mg/kg group (P<0.05), meanwhile the contents of MDA and H2O2 increased in 2.50 and 5.00mg/kg groups (P<0.05). The protein expression levels of Bax and ratio of Bax/Bcl-2 in NiSO4 5.00mg/kg group increased significantly compared with control group in rats liver cells (P<0.05). The protein expression level of Cleaved-Caspase3 in rats liver cells increased significantly in NiSO4 2.50 and 5.00mg/kg groups compared with control group (P<0.05), and the Pro-Caspase3 in NiSO4 5.00mg/kg group was significantly lower than that of control group (P<0.05). (2) GSPE could have the protective effect for rats liver cells, the organ coefficient increased in GSPE 50 and 200mg/kg groups compared with NiSO4 model group (P<0.05). The levels of MDA and H2O2 were lower than that of NiSO4 model group in GSPE 100 and 200mg/kg groups. The protein expression level of Cleaved-Caspase-3 and ratio of Bax/Bcl-2 were significantly lower than that of NiSO4 model group in GSPE 200mg/kg group (P<0.05). Conclusion The results showed that excess nickel exposure can induce adverse effects of liver cells that could be related to oxidative damage and abnormal protein expression of Bax, Bcl-2 and Caspase-3 and GSPE could have some protective effects on liver injury induced by nickel sulfate in male rats.