The protective effect of resveratrol on dimethylnitrosamine-induced liver fibrosis in rats.
Oxidative stress in liver injury is a major pathogenetic factor in progress of liver fibrosis. Resveratrol, a representative antioxidant derived from grapes, has been reported to show widespread pharmacological properties. In this study, we investigated the protective effects of resveratrol on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Rats were treated with resveratrol daily by oral gavage for seven days after a single intraperitoneal injection of DMN (40 mg/kg). Resveratrol remarkably recovered body and liver weight loss due to DMN-induced liver fibrosis. Liver histology showed that resveratrol alleviated the infiltration of inflammatory cells and fibrosis of liver tissue. Resveratrol decreased the level of malondialdehyde and increased the levels of glutathione peroxidase and superoxide dismutase. Also, resveratrol significantly inhibited the mRNA expression of inflammatory mediators including inducible nitric oxide, tumor necrosis factor-alpha and interleukin-1beta. In addition, resveratrol showed not only reduced mRNA expression of fibrosis-related genes such as transforming growth factor beta 1, collagen type I, and alpha-smooth muscle actin, but also a significant decrease of hydroxyproline in rats with DMN-induced liver fibrosis. Our results suggest that resveratrol could be used to treat liver injury and fibrosis and be useful in preventing the development of liver fibrosis and cirrhosis.
Hong
Sang-Won
SW
Department of Biomedical Sciences and Clinical Research Center, College of Medicine, Inha University, Incheon, 400-711, Korea.
Jung
Kyung Hee
KH
Zheng
Hong-Mei
HM
Lee
Hee-Seung
HS
Suh
Jun-Kyu
JK
Park
In-Suh
IS
Lee
Don-Haeng
DH
Hong
Soon-Sun
SS
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004128:Dimethylnitrosamine; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000627:therapeutic use*
D000975:Antioxidants; D015415:Biomarkers; D013267:Stilbenes; D004128:Dimethylnitrosamine; D000077185:Resveratrol