dose-dependent hepatotoxicity effects of zinc oxide nanoparticles

objective(s):   zinc oxide nanoparticles (znp) are increasingly used in sunscreens, biosensors, food additives and pigments. in this study the effects of znp on liver of rats was investigated.     materials and methods: experimental groups received 5, 50 and 300 mg/kg znp respectively for 14 days. control group received only distilled water. alt, ast and alp were considered as biomarkers to indicate hepatotoxicity. lipid peroxidation (mda), sod and gpx were detected for assessment of oxidative stress in liver tissue. histological studies and tunel assay were also done.  results:   plasma concentration of zinc (zn) was significantly increased in 5 mg/kg znp-treated rats. liver concentration of zn was significantly increased in the 300 mg/kg znp-treated animals. weight of liver was markedly increased in both 5 and 300 mg/kg doses of znp. znp at the doses of 5 mg/kg induced a significant increase in oxidative stress through the increase in mda content and a significant decrease in sod and gpx enzymes activity in the liver tissue. administration of znp at 5 mg/kg induced a significant elevation in plasma ast, alt and alp. histological studies showed that treatment with 5 mg/kg of znp caused hepatocytes swelling, which was accompanied by congestion of rbc and accumulation of inflammatory cells. apoptotic index was also significantly increased in this group. znp at the dose of 300 mg/kg had poor hepatotoxicity effect.  conclusion:  it is concluded that lower doses of znp has more hepatotoxic effects on rats, and recommended to use it with caution if there is a hepatological problem.