title: Resveratrol mitigate structural changes and hepatic stellate cell activation in N'-nitrosodimethylamine-induced liver fibrosis via restraining oxidative damage.
abstract: Resveratrol, a polyphenol, found in skin of red grapes, peanuts and berries possesses anti-inflammatory, anti-carcinogenic and lipid modulation properties. Here, we demonstrate in vivo antifibrotic activity of resveratrol in a mammalian model, wherein hepatic fibrosis was induced by N'-nitrosodimethylamine (NDMA) administration. Apart from being a potent hepatotoxin, NDMA is a known mutagen and carcinogen, as well. To induce hepatic fibrosis, rats were administered NDMA (i.p.) in 10mg/kgb.wt thrice/week for 21 days. Another group of animals received resveratrol supplement (10mg/kgb.wt) subsequent to NDMA administration and were sacrificed weekly. The changes in selected biomarkers were monitored to compare profibrotic effects of NDMA and antifibrotic activity of resveratrol. The selected biomarkers were: sera transaminases, ALP, bilirubin, liver glycogen, LPO, SOD, protein carbonyl content, ATPases (Ca(2+), Mg(2+), Na(+)/K(+)) and hydroxyproline/collagen content. Alterations in liver architecture were assessed by H&E, Masson's trichrome and reticulin staining of liver biopsies. Immuno-histochemistry and immunoblotting were employed to examine expression of α-SMA. Our results demonstrate that during NDMA-induced liver fibrosis transaminases, ALP, bilirubin, hydroxyproline and liver collagen increases, while liver glycogen is depleted. The decline in SOD (>65%) and ATPases, which were concomitant with the elevation in MDA and protein carbonyls, strongly indicate oxidative damage. Fibrotic transformation of liver in NDMA-treated rats was verified by histopathology, immuno-histochemistry and immunoblotting data, with the higher expressivity of α-SMA-positive HSCs being most established diagnostic immuno-histochemical marker of HSCs. Resveratrol-supplement refurbished liver architecture by significantly restoring levels of biomarkers of oxidative damage (MDA, SOD, protein carbonyls and membrane-bound ATPases). Therefore, we conclude that antifibrotic effect of resveratrol is due to restrained oxidative damage and down-regulation of α-SMA, which inhibits HSC activation to obstruct liver fibrosis.
authors: Biochemical and Clinical Genetics Laboratory, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, U.P., India.
authors: Areeba
authors: A
authors: Ahmad
authors: Biochemical and Clinical Genetics Laboratory, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, U.P., India. Electronic address: riazzool@rediffmail.com.
authors: Riaz
authors: R
authors: Ahmad
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D015153:Blotting, Western; D004128:Dimethylnitrosamine; D015180:Electrophoresis, Gel, Two-Dimensional; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000188:drug therapy; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013267:Stilbenes; D004128:Dimethylnitrosamine; D000077185:Resveratrol
keywords: ATPases; Liver fibrosis; N′-Nitrosodimethylamine; Oxidative damage; Resveratrol; α-Smooth muscle actin