Targeting PI3K/Akt/Nrf2 pathway by glabridin alleviates acetaminophen-induced hepatic injury in rats

Abstract

Acetaminophen (APAP) induced liver injury is a leading cause for drug-induced liver damage. Glabridin is an isoflavonoid that is reported to possess anti-inflammatory and oxidative stress preventing effects. The aim of this study was to evaluate the protective effects of glabridin against APAP-induced liver injury in rats. Rats were pre-administered with glabridin (30 mg/kg, p.o.; 7 days) followed by single dose of APAP (500 mg/kg, i.p.; 7th day) one hour after glabridin administration. The resulting levels of liver enzymes (AST, ALT, ALP), lipid peroxidation, antioxidant enzymes (CAT, GPx, SOD, GST), reduced glutathione (GSH), inflammatory mediators (TNF-α, IL-6, IL-1β), and apoptosis regulator proteins (casp-3, casp-9, Bcl2, Bax) were determined. Oxidative stress, inflammation and apoptosis triggered due to APAP-induced liver injury were significantly alleviated (p < 0.05) by glabridin. Western blot analysis showed the regulatory effect of glabridin on phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and Nrf2/HO-1 protein expressions against APAP-induced toxicity. Histopathological (H&E) data provided evidence for the protective effect of glabridin on rat liver tissue from injury caused by APAP. In conclusion, the protective effect of glabridin on APAP-induced liver injury was exerted by activating the PI3K/Akt/Nrf2/HO-1 pathway, inhibiting oxidative stress, inflammation, and apoptosis.

Keywords

• Glabridin
• Apoptosis
• Inflammation
• Oxidative stress
• Liver injury