L-carvone protects against myoglobinuric acute tubular necrosis via inhibition of NF-κB and caspase-dependent apoptotic pathways
Year: 2026
Type: article
Abstract: Background: Acute kidney injury (AKI) secondary to rhabdomyolysis is a life-threatening clinical condition characterized by oxidative stress, inflammation, and tubular cell apoptosis. Effective pharmacological treatments targeting these pathophysiological cascades remain limited. Objective: This study aimed to investigate the nephroprotective effects of the natural monoterpene L-carvone in a murine model of glycerol-induced rhabdomyolysis-associated AKI. Methods: Fifty male BALB/c mice were assigned to five groups (n = 10/group): control, rhabdomyolysis (50% glycerol, 10 mL/kg), and three groups receiving prophylactic oral L-carvone (25, 50, or 100 mg/kg) for five days prior to glycerol administration. Renal function was evaluated via blood urea nitrogen (BUN), creatinine, and myoglobin. Tubular injury (KIM-1, NGAL), inflammatory gene expression (IL-1β, TNF-α, NF-κB), apoptotic protein expression (BAX, BCL-2, caspase-8, cleaved caspase-3), and renal histopathology were analyzed. Results: L-carvone pretreatment significantly lowered serum BUN, creatinine, and myoglobin levels compared to the untreated rhabdomyolysis group. Furthermore, L-carvone markedly reduced the expression of tubular injury biomarkers KIM-1 and NGAL. RT-qPCR analysis demonstrated that L-carvone substantially decreased mRNA levels of pro-inflammatory mediators IL-1β, TNF-α, and NF-κB. Western blot analysis revealed a strong anti-apoptotic shift, characterized by decreased BAX, caspase-8, and cleaved caspase-3, alongside significantly increased BCL-2. These molecular improvements strongly correlated with significantly preserved renal histopathological architecture. Conclusion: L-carvone provides robust renal protection against glycerol-induced rhabdomyolysis by attenuating key inflammatory and apoptotic signaling pathways. These preclinical findings highlight its therapeutic potential as a promising candidate for the management of rhabdomyolysis-associated AKI.
Source: Toxicology Reports
Institutions: University of Baghdad, Ministry of Health
Language: English
Topic: Acute Kidney Injury Research
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,530
OpenAlex ID: W7160280450