Effects and mechanisms of sub-chronic exposure to copper nanoparticles on renal cytochrome P450 enzymes in rats

Copper nanoparticles (Cu NPs) have widespread application because of their special physicochemical characteristics, however we need to more clearly study the toxicity mechanism of Cu NPs to ensure its safe use in pharmaceutical and animal feed. Thus, the aim of this study was to evaluate the effects and mechanisms of sub-chronic exposure to Cu NPs on renal CYP450 s of rats. In this study, we investigated the effects of Cu NPs on renal oxidative stress, cytokines and histopathology of rats. We found that Cu NPs (200 mg/kg) significantly disordered the function and structure of the kidney and caused a dose-dependent increase in oxidative stress and cytokines, which significantly decreased the levels of mRNA, protein, and activity of CYP450 s. Micro-coppers (Cu MPs) and Cu ions have similar effects, but their effects on CYP450 s were weaker than Cu NPs. The expression of nuclear receptors were inhibited and the expression of Akt, STAT3/5, CREB, p70S6K, NF-κB, P38 and ERK1/2 were activated when the inhibition effects of CYP450 s activity were observed in renal of rats. Therefore, we believe that Cu NPs can activate the STAT, NF-κB and MAPK signaling pathways to down-regulate the expression and activity of CYP450 s by inducing oxidative stress and inflammatory response in rat kidney.