Quercetin-targeted AKT1 regulates the Raf/MEK/ERK signaling pathway to protect against doxorubicin-induced nephropathy in mice

Background: Doxorubicin is an anthracycline antitumor agent commonly used in clinical practice, which has some nephrotoxicity and is often used to establish mouse models of kidney injury for basic medical research. This study will investigate the protective effect of quercetin on renal function in doxorubicin-induced nephropathy mice.Methods: C57BL/6 mice were divided into control, model, and quercetin low-, and high-dose groups. Serum and urine were collected to analyze markers of kidney function. H&E staining was used to detect pathological changes in renal tissues. Transmission electron microscopy was performed to observe the ultrastructural changes in renal tissues. Immunohistochemistry was performed to detect the changes of Ang II. RT-qPCR was performed to detect the changes of cytokines. ELISA was used to detect changes in serum inflammatory factors. Molecular docking was performed to verify the targeting relationship between quercetin and AKT1. Western blot was performed to detect Bax, Bcl-2, Cyt-c, AKT1, Raf, MEK, and ERK proteins.Results: Quercetin could induce the recovery of kidney function in kidney-injured mice; H&E results showed that kidney tissue damage and tissue fibrosis were reduced in kidney-injured mice under quercetin. The mitochondrial swollen structure was destroyed by doxorubicin, while the mitochondrial structure was restored under quercetin. The levels of abnormal apoptotic proteins Bax and Bcl-2 were regulated to normal by quercetin. The high expression of Ang II caused by doxorubicin was down-regulated by quercetin. Abnormal inflammatory factors caused by doxorubicin were reversed by quercetin. Western blot experiments showed that quercetin regulated the protein levels of AKT1 and Raf/MEK/ERK and inhibited the detrimental effects of doxorubicin.Conclusion: Quercetin may mitigate doxorubicin-induced kidney injury in mice by regulating renal cell inflammatory factors and Raf/MEK/ERK signaling pathway through AKT1 to promote recovery of renal function.

Automated summary

The study found that quercetin can promote the recovery of kidney function in kidney-injured mice. Histopathological results showed that kidney tissue damage and fibrosis were reduced under the action of quercetin. The mitochondrial swollen structure caused by doxorubicin was restored by quercetin. Quercetin regulated the levels of abnormal apoptotic proteins Bax and Bcl-2 to normal levels. The high expression of Ang II caused by doxorubicin was down-regulated by quercetin. Abnormal inflammatory factors caused by doxorubicin were reversed by quercetin. Western blot experiments showed that quercetin regulated the protein levels of AKT1 and Raf/MEK/ERK and inhibited the detrimental effects of doxorubicin.