Quercetin protects cadmium-induced kidney injury by regulating PI3K/AKT/mTOR and Nrf2/NQO1 pathways in rats

Cadmium (Cd) is a hazardous heavy metal widely found in the environment. Quercetin (Que) is a flavonoid antioxidant with biological actions. To elucidate the molecular mechanism of Que alleviating renal injury induced by Cd. CdCl 2 intraperitoneal injection (1 mg/kg b.w.) and/or Que gavage (50 mg/kg b.w.) for 7 days. Renal function and oxidative stress markers were measured, apoptosis, autophagy was measured. Que ameliorated Cd-induced renal dysfunction. Meanwhile, Que alleviated oxidative damage and enhancing antioxidant enzyme activity, it also upregulated Nrf2 and NQO1 expression. In addition, Que significantly decreased the levels of apoptosis-related factors alongside increased Bcl-2 level. More importantly, Que reduced p62 and increased Beclin-1, Atg5, and LC3 levels. This was related to the decrease of PI3K, p-AKT, and p-mTOR protein levels by Que. Que restored autophagy, inhibited oxidative stress and apoptosis, and contributed to the amelioration of Cd-induced nephrotoxicity through inhibition of PI3K/AKT/mTOR and activation of the Nrf2/NQO1 pathway. • Cadmium-induced oxidative stress, autophagy inhibition, and apoptosis in kidney • Quercetin attenuates kidney oxidative damage by upregulating Nrf2/NQO1 pathway • Quercetin down-regulates PI3K/AKT/mTOR pathway to restore autophagy • Quercetin has a protective effect on cadmium-induced renal injury