title: Naringenin attenuates CCl4 -induced hepatic inflammation by the activation of an Nrf2-mediated pathway in rats.
abstract: The possible protective effects of naringenin, a naturally occurring citrus flavonone, on carbon tetrachloride (CCl4 )-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 CCl4 . In addition, naringenin increased the liver content of reduced glutathione and the activity of anti-oxidant enzymes in rats treated with CCl4 . Naringenin attenuated liver inflammation by downregulating CCl4 -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 CCl4 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.
authors.affiliation: Department of Biology, Medicinal Plants and Drug Research Institute, Shahid Beheshti University, Tehran, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Esmaeili
authors.forename: Mostafa
authors.initials: M
authors.lastname: Alilou
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced* / Q000517:prevention & control; D015394:Molecular Structure; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D012838:Silymarin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D044950:Flavanones; D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride; C005273:naringenin
keywords: carbon tetrachloride; hepatotoxicity; inflammation; naringenin