Quercetin alleviated cadmium-induced oxidative stress, endoplasmic reticulum stress, and autophagy in chicken kidneys

Cadmium (Cd) is a toxic carcinogen that severely damages many tissues and organs. Quercetin (Que) is a flavonol known for its excellent antioxidant properties. Forty-eight 1-day-old male Hyland egg-laying chickens were assigned to the following treatments: control group; 150 mg/kg Cd group; 250 mg/kg Que group; and 150 mg/kg Cd + 250 mg/kg Que group. The experimental results confirmed that the histopathological observation of the kidneys in Cd-exposed chickens showed blurred glomerular contour, enlarged lumen, and a significant increase in renal function indicators such as Uric Acid (UA), Creatinine (Cr), Blood Urea Nitrogen (BUN), and β-N-acetylglucosaminidases (NAG), indicating Cd-induced nephrotoxicity, while Que alleviated the Cd-induced nephrotoxicity. Cd induces renal oxidative stress by reducing Catalase (CAT), Total Superoxide Dismutase (T-SOD), and Total antioxidant capacity (T-AOC) levels, while increasing Malondialdehyde (MDA) and Glutathione (GSH) levels. Meanwhile, Cd induced renal endoplasmic reticulum (ER) stress and autophagy by up-regulating the expression of GRP78, PERK, p-PERK, ATF4, ATF6, CHOP, eIF2α, p-eIF2α, and LC3, and down-regulating p62. Furthermore, immunohistochemistry (IHC) analysis confirmed the positive expression of the autophagy markers LC3 and p62, consistent with the aforementioned findings. Interestingly, Que inhibits the ER stress and autophagy genes mentioned above, and upregulates p62, thereby alleviating Cd-induced oxidative stress, ER stress, and autophagy. This study found that Cd-induced ER stress occurred earlier than autophagy in the kidneys of chickens. Overall, this study elucidated the protective effect of Que on Cd-induced kidney injury, and the mechanisms involved oxidative stress, ER stress, and autophagy.