Role of oxidative stress in liver toxicity induced by nickel oxide nanoparticles in rats.

The aim of the present study was to explore the role of oxidative stress in liver toxicity induced by nickel oxide nanoparticles (nano‑NiO) in rats. Male Wistar rats received saline (control), nano‑NiO [0.015, 0.06 or 0.24 mg/kg body weight (b.w.)] or micro‑NiO (0.24 mg/kg b.w.) by intratracheal instilling twice a week for 6 weeks. Liver tissues were then collected and examined for biomarkers of nitrative and oxidative stress, as well as mRNA expression of heme oxygenase (HO)‑1 and metallothionein (MT)‑1. The results demonstrated that the NiO exposure groups had increased liver wet weight and coefficient to body weight, as well as liver pathological changes, evidenced as cellular edema, hepatic sinus disappeara-nce and binucleated hepatocytes. The activities of total nitric oxide synthase and inducible nitric oxide synthase, and the nitric oxide content, were increased in the 0.24 mg/kg nano‑NiO group compared with the control group. The MT‑1 mRNA expression levels were downregulated, while HO‑1 mRNA was upregulated in the 0.24 mg/kg nano‑NiO exposure group compared with the control group. In addition, abnormal changes of hydroxyl radical, lipid peroxidation, catalase, glutathione peroxidase, total superoxide dismutase and total antioxidative capacity were observed in the liver tissues of the 0.24 mg/kg nano‑NiO exposure group, compared with the control group. The present results therefore indicated that nano‑NiO‑induced liver toxicity may be associated with nitrative and oxidative stress in rats.