Evaluation of the Protective Effects of Liquiritigenin against Glycerol-Induced Acute Kidney Injury in Male Rabbits

Abstract Abstract Background: Acute kidney injury (AKI) is a critical clinical condition characterized by a sudden loss of kidney function. It's commonly associated with rhabdomyolysis (RML), often resulting from myoglobin release. This leads to oxidative stress, inflammation, endothelial damage, and tubular necrosis. Currently, therapeutic options for AKI are limited, spurring interest in natural compounds with nephroprotective effects. Objective: This study investigates the protective effects of Liquiritigenin (LQ), a licorice-derived flavonoid, on glycerol (GLY)-induced AKI, an established model for RML-related renal injury, focusing on its potential to reduce renal damage via antioxidant and anti-inflammatory mechanisms. Materials and Methods: Sixty male albino rabbits were divided into five groups: control, induction group (AKI group), vehicle group, and two treatment groups receiving LQ at 30 mg/kg and 50 mg/kg. GLY-induced AKI was established by administering a single intramuscular injection of hypertonic glycerol. Biochemical analyses included measurements of serum creatinine, urea, creatine kinase (CK), electrolytes, oxidative stress markers (glutathione peroxidase [GPx1] and malondialdehyde [MDA], and inflammatory cytokines (IL1β, IL6, TNF-α). Kidney tissues were examined histologically to assess structural damage. Results: The GLY-induced AKI group exhibited significantly elevated serum creatinine, urea, CK, proinflammatory cytokines, and MDA, alongside decreased GPx1 levels and substantial histopathological damage. In contrast, the LQ treatment groups, especially at 50 mg/kg, showed significant reductions in serum creatinine, urea, CK levels, and inflammatory cytokines, with a notable improvement in GPx1 and a decrease in MDA levels. Electrolyte imbalances observed in the GLY group were also restored, in the LQ-treated groups. Histopathological analysis revealed decreased tubular injury and overall tissue recovery in the LQ-treated groups. Conclusions: LQ demonstrated significant nephroprotective effects in GLY-induced AKI, likely through attenuation of oxidative stress and inflammatory pathways. These findings position LQ as a promising therapeutic candidate for managing AKI, particularly in cases associated with RML.