Chlorogenic acid, quercetin, coenzyme Q10 and silymarin modulate Keap1-Nrf2/heme oxygenase-1 signaling in thioacetamide-induced acute liver toxicity

Abstract

Background and aimsThe normal functioning of Kelch-like ECH-associated protein-1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) complex is necessary for the cellular protection against oxidative stress. We investigated the effect of chlorogenic acid (CGA), quercetin (Qt), coenzyme Q10 (Q10) and silymarin on the expression of Keap1/Nrf2 complex and its downstream target; heme oxygenase-1 (HO-1) as well as inflammation and apoptosis in an acute liver toxicity model induced by thioacetamide (TAA). Main methodsWistar rats were divided into 13 groups: Control, silymarin, CGA, Qt, Q10, TAA (single dose 50 mg/kg, i.p.), TAA + silymarin (400 mg/kg, p.o.), TAA + CGA (100 & 200 mg/kg, p.o.), TAA + Qt (200 &300 mg/kg, p.o.) and TAA+ Q10 (30&50 mg/kg, p.o.) and treated for 8 days. Key findingsThe results showed improved liver functions and hepatic tissue integrity in all tested doses of TAA + silymarin, TAA + CGA, TAA + Qt and TAA + Q10 groups compared to the TAA group. Furthermore, these groups showed significantly lower ROS, malondialdehyde and nitric oxide levels but higher glutathione content and superoxide dismutase activity compared to the TAA group, p < 0.05. In these groups, Keap1 expression was significantly decreased while Nrf2 expression and HO-1 activity were increased. In addition, the number of apoptotic cells and the expression level of TNF-α in the liver tissues were significantly decreased compared to the TAA group. SignificanceCGA, Qt, Q10 and silymarin protect against TAA-induced acute liver toxicity via antioxidant, anti-inflammatory, anti-apoptotic activities and regulating Keap1-Nrf2/HO-1 expression.