Naringenin attenuates CC l 4 ‐induced hepatic inflammation by the activation of an Nrf2‐mediated pathway in rats

Summary The possible protective effects of naringenin, a naturally occurring citrus flavonone, on carbon tetrachloride (CCl 4 )‐induced liver injury in rats and the mechanism underlying its effects were investigated. Forty rats were divided into five groups. Rats in Groups I and II served as the normal and injured liver groups, respectively; Group III rats were treated with the standard drug silymarin as a positive control; and rats in Groups IV and V (naringenin‐treated groups) were administrated 50 mg/kg, p.o., naringenin for 7 days. Liver samples were collected to evaluate mRNA and protein expression, histological changes and oxidative stress. Naringenin inhibited lipid peroxidation and reduced serum levels of hepatic enzymes induced by CCl 4 . In addition, naringenin increased the liver content of reduced glutathione and the activity of anti‐oxidant enzymes in rats treated with CCl 4 . Naringenin attenuated liver inflammation by downregulating CCl 4 ‐induced activation of tumour necrosis factor (TNF)‐ α , inducible nitric oxide synthase ( iNOS ) and cyclo‐oxygenase (COX‐2) at both the protein and mRNA levels. Naringenin treatment significantly increased NF‐E2‐related factor 2 (Nrf2) and heme oxygenase (HO‐1) expression in injured livers. In rats treated with CCl 4 alone, decreases were seen in nuclear Nrf2 expression and in the mRNA levels of its target genes (e.g. HO‐1 , NQO1 and glutathione S‐transferase alpha 3 ( GST‐a3 )). Together, the results suggest that naringenin can protect the liver against oxidative stress, presumably by activating the nuclear translocation of Nrf2 as well as attenuating the TNF‐ α pathway to elicit an anti‐inflammatory response in liver tissue.