Naringenin attenuates CCl4‐induced hepatic inflammation by the activation of an Nrf2‐mediated pathway in rats. (June 2014)

• Record Type: Journal Article
• Authors: Esmaeili, Mohammad Ali; Alilou, Mostafa
• Is Part Of: Clinical and experimental pharmacology and physiology. Volume 41:Number 6(2014:Jun.)
• Page Start: 416
• Page End: 422
• Publication Date: 2014-06
• Subjects: Clinical pharmacology -- Periodicals; Pharmacology, Experimental -- Periodicals; Physiology, Experimental -- Periodicals; Physiology, Pathological -- Periodicals; 615.1
• DOI: 10.1111/1440-1681.12230
• Languages: English
• ISSNs: 0305-1870

Abstract

<abstract abstract-type="main" id="cep12230-abs-0001"> <title>Summary</title> <p>The possible protective effects of naringenin, a naturally occurring citrus flavonone, on carbon tetrachloride (CCl<sub>4</sub>)‐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<sub>4</sub>. In addition, naringenin increased the liver content of reduced glutathione and the activity of anti‐oxidant enzymes in rats treated with CCl<sub>4</sub>. Naringenin attenuated liver inflammation by downregulating CCl<sub>4</sub>‐induced activation of tumour necrosis factor (TNF)‐<italic>α</italic>, 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<sub>4</sub> alone, decreases were seen in nuclear Nrf2 expression and in the mRNA levels of its target genes (e.g. <italic>HO‐1</italic>, <italic> NQO1</italic> and glutathione S‐transferase alpha 3 (<italic>GST‐a3</italic>)). 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‐<italic>α</italic> pathway to elicit an anti‐inflammatory response in liver tissue.</p> </abstract>