Antagonistic effects of titanium dioxide nanoparticles on cadmium-induced nephrotoxicity and intestinal flora imbalance by reducing its bioavailability in rats

Titanium dioxide nanoparticles (nTiO 2 ) possess unique physicochemical properties, such as large specific surface area, enabling heavy metals adsorption like Cadmium (Cd), yet the combined risks to the ecosystem and human remain unclear. This 90-day study explored the combined effects of nTiO 2 (at a population-relevant dose of 100 mg/kg body weight administered via gavage) and cadmium chloride (CdCl 2 ) (50 mg Cd/L by drinking water) on kidney and gut microbiota of rats. Co-exposure of nTiO 2 and Cd significantly reduced the nephrotoxicity induced by Cd, with lower levels of urine biochemical indicators and Cd content, milder histopathological changes and ultrastructural damage. A two-way ANOVA analysis suggested antagonism between nTiO 2 and Cd on urinary creatinine (CRE) and Urea. Coincidentally, gut microbiota remained unaffected by nTiO 2 but was disrupted by Cd. Co-exposure also partially alleviated the adverse changes, restoring the decreased Beta-diversity and the relative abundance of bacteria to control levels. Furthermore, co-exposure resulted in a 19.2 % decline in the blood Cd concentration and an 8.6 % reduction in kidney, while the Cd content of 24 h feces was 3.6 % higher. These findings suggested antagonistic effects of nTiO 2 against Cd-induced nephrotoxicity and intestinal flora disorder in rats. The effects might be attributed to the adsorption of nTiO 2 on Cd, which resulted in the reduced Cd intake and distribution, coupled with increased excretion, thereby decreasing the Cd bioavailability. This study provides new evidence for understanding the impacts of nTiO 2 and Cd on mammals and will contribute to the further risk assessments of co-exposure to human health and environment safety.