Zinc oxide nanoparticles cause hepatotoxicity in rare minnow (Gobiocypris rarus) via ROS-mediated oxidative stress and apoptosis activation and inhibition of lipid peroxidation

Abstract

Zinc oxide nanoparticles (ZnO NPs) measuring 30 ± 10 nm in diameter are utilized in various applications, including batteries, plastics, ceramics, cosmetics, flame retardants, and food. However, their potential impact and risk on aquatic ecosystems remain unclear. This study examined the hepatotoxic effects of dietary ZnO NPs in rare minnow. Three hundred rare minnows were fed diets containing 0 mg/kg, 20 mg/kg and 60 mg/kg of ZnO NPs for 60 days, with hepatotoxicity assessments at 15-day intervals. The histological data showed that ZnO NPs severely damage liver tissues, causing cytoplasmic vacuolization and irregular or missing nuclei. The treatment groups showed a significant rise in the liver injury index (P < 0.05). Moreover, there was a notable increase in zinc accumulation in the ZnO NPs groups compared to the control group (P < 0.05). ZnO NPs also reduced body weight and hepato-somatic index (HSI) in rare minnows. The enzyme activity results showed elevated levels of reactive oxygen species (ROS), total cholesterol (T-CHO), triglyceride (TG), acetyl Coa carboxylase (ACC), and fatty acid synthase (FAS) in the ZnO NPs fed groups, while total antioxidant capacity (T-AOC) and malondialdehyde (MDA) decreased. Further investigation found that accumulation of ZnO NPs in the liver tissues up-regulated the levels of genes related to antioxidant (mn-sod, cat and nf-κb), pro-apoptotic (bax) and lipogenesis (gpat3, dgat1a and dgat1b), while down-regulating genes associated with lipid catabolism (cpt1 and tpi1). These findings suggest that dietary ZnO NPs cause hepatotoxicity by inducing oxidative stress through ROS, triggering apoptosis, and inhibiting lipid peroxidation. The results indicate that ZnO NPs may pose a significant threat to aquatic animals and ecosystems.