Nickel chloride-induced ROS cause cyto- and geno-toxicity in rat intestine: a biochemical and histological study.

Nickel (Ni) is a significant environmental pollutant that poses a risk to human health due to its carcinogenic nature which involves DNA damage, oxidative stress, and disruption of cellular signaling pathways. These effects contribute to the development of lung, nasal, and sinonasal cancers, as well as damage to various tissues and organs. Nickel chloride (NiCl₂), an inorganic divalent Ni compound, has been reported to induce oxidative stress in cellular systems by disrupting redox homeostasis. This study aimed to  investigate the effect of a single acute oral dose of NiCl₂ on the rat small intestine, especially on the antioxidant defence system and DNA integrity. Male Wistar rats were divided into five groups: one control (untreated) and four NiCl₂-treated groups, each receiving single oral dose of NiCl₂ at 45, 90, 135, and 180 mg/kg body weight. NiCl₂ treatment diminished the content of reduced glutathione and total sulfhydryl groups but increased lipid and protein oxidation and also hydrogen peroxide levels. The antioxidant power of the intestine was compromised due to inhibition of key antioxidant enzymes and decreased reduced glutathione levels which led to impaired free radical quenching and metal-reducing ability. Oral administration of NiCl₂ inhibited the marker enzymes of intestinal brush border membrane. Enzymes of pathways of carbohydrate metabolism like glycolysis, gluconeogenesis, citric acid cycle, and hexose monophosphate shunt were also inhibited. The diphenylamine and comet assays showed significantly increased DNA fragmentation, while DNA-protein cross-linking in intestinal mucosa of NiCl₂-administered animals was also elevated, when compared to the control group. Histopathology showed abnormal morphology of intestinal villi with marked lymphocytic infiltration in NiCl₂-treated rats. This is likely due to increased ROS production and oxidative damage of cell components. All changes were seen in a NiCl₂ dose-dependent manner. The observed intestinal damage could be due to significant impairment in the antioxidant defence system elicited by oxidative stress produced upon exposure to NiCl₂ with more prominent changes at higher doses of the metal ion.