β-hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating Camkk2 Mediated Ferroptosis
Description
Background: Cisplatin is a highly effective antineoplastic drug. However, the application of cisplatin is limited by cisplatin-induced nephrotoxicity. Recent researches have suggested that β-hydroxybutyrate (β-HB) works as a therapeutic agent protected against acute or chronic organ damage effectively. However, therapeutic mechanisms of β-HB on chemotherapy drugs inducing acute kidney injury remain elusive. Methods: Our research established a cisplatin-induced acute kidney injury (AKI) model, with β-HB or high fat diet administration. Blood urea nitrogen (BUN) and creatinine (Cr) in serum were tested, western blotting and immunohistochemical staining were used to evaluate ferroptosis and Camkk2. We further using HK-2 cells to clarify the effects of β-HB on ferroptosis and Camkk2 in vitro. Results: Simultaneously, cisplatin-induced abnormally elevation of BUN, Cr and renal tubular necrosis were significantly alleviated by exogenous or endogenous β-HB in vivo. In addition, β-HB also reduced ferroptosis biomarkers and increased anti-ferroptosis biomarkers in kidney. β-HB significantly attenuated cisplatin-induced cell ferroptosis and damage in vitro. Moreover, western blotting and immunohistochemical staining indicated that β-HB may prevent kidney injury through regulating the Camkk2. Conclusion: This study revealed protective effects of β-HB on cisplatin-induced nephrotoxicity, the newly potential molecular mechanisms underlying were inhibited ferroptosis and Camkk2.