Protective Effects of Glycyrrhizic Acid and 18β-Glycyrrhetinic Acid against Cisplatin-Induced Nephrotoxicity in BALB/c Mice

The clinical use of antineoplastic drug cisplatin (CP) is commonly complicated by nephrotoxic side effects that limit its application and therapeutic efficiency. This study used a model of CP-induced renal injury in male BALB/c mice to investigate the protective effects of the active components of licorice, glycyrrhizic acid (GA), and 18β-glycyrrhetinic acid (18βGA) against CP-induced nephrotoxicity, and the chemoprotectant, amifostine, was used as a control. Oral administration of GA or 18βGA significantly reduced CP-induced increases in the levels of blood urea nitrogen, creatinine, and lactate dehydrogenase. Hematoxylin and eosin staining revealed that GA and 18βGA delayed the progression of renal injury, including tubular necrosis, hyaline casts, and tubular degeneration in response to CP exposure. Oxidative status and inflammatory responses in CP-treated mice were restored to near-normal levels by treatment with GA or 18βGA. These protective effects might be associated with upregulation of nuclear factor E2-related protein (Nrf2) and downregulation of nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κB) in the kidney. Notably, we demonstrated that GA and 18βGA rendered renal cells resistant to CP-induced HMGB1 cytoplasmic translocation and release. These findings suggest that GA and 18βGA might be act as the chemoprotectants against CP-induced nephrotoxicity.