Synergistic and antagonistic effects of nickel and cadmium on oxidative stress and Ca2+-ATPase activity in rats

Abstract Background Humans, plants, and animals are often exposed to metal mixtures rather than individual metals, yet the toxicological effects of such mixtures remain underexplored. This study investigates the effects of Nickel (Ni) and Cadmium (Cd), individually and in combination, on toxicity-associated parameters in male and female Wistar rats. A key focus is whether co-administration of these metals alters their toxicity compared to single-metal exposure. Results The study revealed increased accumulation of Ni and Cd in all test groups, with the highest concentrations in the liver and kidney. However, metal accumulation was higher in female rats. In addition, co-administration resulted in lower organ metal concentrations compared to separate exposures, suggesting antagonistic interactions. Lipid peroxidation (LPO) increased ( p < 0.05) in the kidney, heart, and intestine, while Ca 2 ⁺-ATPase activity decreased in the same organs. Superoxide dismutase (SOD) and glutathione (GSH) levels declined across all test groups, and catalase (CAT) activity was significantly reduced in the kidney but unchanged in other organs. In most of the parameters studied the results indicate metal toxicity was more in female rats due to higher accumulation and less in rats administered a combination of both metals occasioned by antagonistic interactions. Conclusion Female rats exhibited higher metal concentrations and toxicity, potentially explaining their increased susceptibility. Additionally, metal co-administration led to reduced toxicity compared to separate exposures, likely due to antagonistic interactions. This study highlights the importance of investigating metal mixtures rather than single metals to better understand real-world toxicity risks.