Liquiritigenin Protects Against Glycerol-Induced Acute Kidney Injury via Antioxidant and Anti-Inflammatory Mechanisms

Acute kidney injury (AKI) is a critical clinical condition characterized by a sudden loss of kidney function.AKI is commonly associated with rhabdomyolysis (RML), which often results 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.This study investigates the protective effects of Liquiritigenin (LQ), a licorice-derived chiral flavonoid.Due to its simple structure, LQ exhibits good absorption and bioavailability.As a selective estrogen- agonist, it inhibits cytokine gene expression, exerts substantial scavenging activity against reactive species, restores mitochondrial integrity, promotes antioxidant enzyme production, and downregulates cytokine expression.This study investigates the strong antioxidant and anti-inflammatory properties of LQ in a glycerol (GLY)-induced AKI model.Sixty male albino rabbits were divided into five groups: control, AKI-induced group (induction), vehicle group, and two treatment groups treated with LQ (30 mg/kg and 50 mg/kg, respectively).AKI was induced by 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 (IL1, IL6, TNF-).Kidney tissues were examined histologically to assess structural damage.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.LQ demonstrated significant nephroprotective effects in GLY-induced AKI, through the inhibition of oxidative stress-induced tubular injury, downregulation of proinflammatory cytokines, and preservation of renal tubular structure.These findings suggest that LQ is a promising therapeutic candidate for managing AKI, particularly in cases associated with RML.