Subchronic Exposure to Arsenic and Nickel Triggers Nitrosative Stress and Histological Alterations in the Rat Liver

Environmental exposure to heavy metals poses a threat to human health. Several studies documented harmful effects on the liver after arsenic and nickel exposure at concentrations beyond permissible limits. Nevertheless, the impact of a simultaneous exposure to both elements on hepatic biochemistry and histology remains unelucidated. Therefore, this study aimed to evaluate the effects of individual and combined ingestion of arsenic and nickel on the rat liver. Adult males (n = 10/group) received saline (control), 1 mg L^-1 of arsenic, 7 mg L^-1 of nickel, and two metals simultaneously in drinking water for 70 days. The results showed that arsenic at 1 mg L^-1 did not alter ionic and oxidative parameters (p > 0.05), whereas nickel at 7 mg L^-1 increased the proportion of Ca and Cu, the occurrence of protein oxidation, and the Ca²⁺ ATPase activity (p < 0.05). Under our experimental conditions, no alterations were observed in hepatic MDA levels or in serum ALT, AST, and ALP (p > 0.05). Histological alterations in the rat liver after isolated arsenic and nickel exposure, including vascular congestion, hydropic degeneration, and inflammatory infiltrate, were intensified after metal co-exposure. The vascular disorder affected the proportion of hepatic components (blood vessels, sinusoids, cytoplasm, and hepatocytes; p < 0.05) in co-exposed rats. Nickel increased the number of mast cells in exposed and co-exposed rats (p < 0.05). Our findings revealed that subchronic co-exposure to arsenic and nickel triggered nitrosative stress in the liver, culminating in histological alterations involving inflammation and vascular disorders mainly.