Nephroprotective Effect of L-Carvone on a Mouse Model of LPS-Induced Sepsis-Associated Renal Injury via Regulation of TLR4/NF-κB/AP-1/IRF-3 and Nrf2/iNOS Molecular Signaling Cascades.

Background: LPS-evoked endotoxemia triggers systemic inflammation and can cause multi-organ damage, with the kidneys being particularly vulnerable. L-carvone is a natural monoterpene with strong antimicrobial, cytoprotective, and immunomodulatory benefits. Objective: This study was aimed at exploring the influence of L-carvone on LPS-aggravated sepsis-associated renal impairment in mice. Methods: A total of 32 male albino-type mice were randomly divided into six groups: untreated control group, sepsis model group (LPS 10 mg/kg single dose), vehicle group (oral corn oil for 5 days before LPS injection), and three intervention groups orally pre-treated with low (25), moderate (50), or high (100) mg/kg doses of L-carvone for 5 continuous days before LPS challenge. Results: L-carvone markedly decreased levels of KIM-1, BUN, and creatinine, and reversed renal histological aberrations. It downregulated TLR4, NF-κB, AP-1, IRF-3, and iNOS renal expression, while upregulating Nrf2 transcription in a dose-dependent manner, thus decreasing interleukin (IL)-1β and TNF-α concentrations. L-carvone further ameliorated pro-apoptotic Bax levels, increased anti-apoptotic Bcl-2, inhibited MDA production, and enhanced SOD activity. Conclusion: L-carvone effectively mitigates sepsis-related renal impairment by counteracting inflammatory, oxidative, and apoptotic mechanisms, thus supporting its translational therapeutic promise.