18β-glycyrrhetinic acid Mitigates bisphenol A-induced liver and renal damage: Inhibition of TNF-α/NF-κB/p38-MAPK, JAK1/STAT1 pathways, oxidative stress and apoptosis

Bisphenol A (BPA) has been commonly used in various consumer products, including water bottles, food containers, and canned food linings. However, there are concerns about its potential toxicity to human health, particularly its impact on the liver and kidneys. The objective of this research was to investigate the potential ameliorative effects of 18β-glycyrrhetinic acid (GA) against BPA-induced hepatotoxicity and nephrotoxicity in rats. The animals were supplemented with BPA (250 mg/kg b.w.) alone or with GA (50 and 100 mg/kg b.w.) for 14 days. GA treatment alleviated the BPA-induced hepato-renal tissue injuries through reducing the serum ALT, AST and ALP levels, and urea and creatinine levels. GA co-treatment also increased activities of SOD, CAT and GPx enzymes and levels of GSH, and suppressed MDA levels in BPA induced tissues. BPA also induced inflammation by increasing the levels of TNF-α, NF-κB, JAK1, STAT1, P38 MAPK and JNK in liver and kidney tissues and GA treatment ameliorated these effects. BPA triggered apoptosis by increasing caspase-3, Bax, and cytochrome c at protein levels and also by decreasing the antiapoptotic Bcl-2 level. However, treatment with GA (50 and 100 mg/kg) decreased apoptosis. Overall, our results have revealed the potential ameliorative mechanisms of GA, as a possible agent for BPA-induced hepatotoxicity and nephrotoxicity.