Glycyrrhizic acid attenuates cisplatin-induced nephrotoxicity: anti-inflammatory mechanisms and renoprotective effects in Wistar rats

Abstract

This study explored the renoprotective effect of glycyrrhizic acid (GA) in a Wistar rat model of cisplatin (CDDP)- induced nephrotoxicity, focusing on its anti-inflammatory mechanisms. Thirty-five male rats were divided into five groups: saline control, ethanol vehicle, GA (100 mg/kg/day, i.p., for 7 days), CDDP (10 mg/kg, i.p., single dose), and GA + CDDP. GA was administered once daily, and CDDP was injected on the second day. Renal function was assessed by measuring serum creatinine, BUN, and urinary KIM-1, while inflammatory markers including IL-1β, IL-18, TNF-α, NF-κB, TLR4, and TLR9 were evaluated using ELISA. Histopathological assessment was performed using H&E staining. CDDP significantly elevated BUN, creatinine, and KIM-1 levels, accompanied by increased expression of IL-1β, TNF-α, NF-κB, and TLR4. GA administration attenuated these alterations, indicating reduced renal damage and inflammation. No significant effects were observed on IL-18 or TLR9 levels. Histological examination revealed that GA treatment helped preserve tubular structure and reduce tissue injury. These results indicate that the protective effects of GA in this model may be linked to its ability to downregulate inflammatory mediators, particularly those involving NF-κB and TLR4. Based on these findings, GA holds promise as a supportive intervention to lessen cisplatin-associated renal toxicity during chemotherapy.