Quercetin protects cadmium-induced renal injury in mice by inhibiting pyroptosis

Abstract

Abstract The heavy metal pollutant cadmium (Cd) is frequently found in the environment and is highly toxic, particularly affecting the kidneys. It remains unclear whether the non-toxic flavonoid quercetin can counteract Cd-induced renal pyroptosis. In this study, we established a model of cadmium poisoning treated with quercetin both in vitro (using mouse renal MES-13 cells at a concentration of 5 µM for 24 h) and in vivo (10 Kunming mice receiving 1 mg/kg body weight via oral gavage for 4 weeks). In vitro experiments revealed that cell viability significantly decreased after exposure to different concentrations of Cd for 12h and 24h, following a concentration-time dependent pattern. Furthermore, treatment with Cd led to a significant increase in cleaved caspase-1, NLRP3, and IL-1β protein levels in MES-13 cells (P < 0.01), which was effectively alleviated by quercetin treatment. In vivo studies demonstrated that Cd significantly elevated blood urea nitrogen levels while reducing GPX and SOD levels. Pathological sections revealed tubular stenosis and renal interstitial congestion as characteristic damage caused by Cd exposure. Notably, Cd-induced renal cell pyroptosis protein cleaved caspase-1 was significantly increased, however, quercetin administration could mitigate these injuries induced by Cd exposure through decreasing caspase-1 protein expression and inhibiting renal cell pyroptosis. Collectively, our findings indicate that kidney cells are susceptible to pyroptotic cell death due to Cd exposure possibly mediated by ROS production leading to oxidative cellular damage followed by activation of caspase-1; meanwhile, quercetin exhibits protective effects against kidney injuries induced by Cd through inhibition of kidney cell pyroptosis.