title: Ameliorative effect of grape seed proanthocyanidin extract on thioacetamide-induced mouse hepatic fibrosis.
abstract: The present study was designed to examine the effect of the grape seed proanthocyanidin extract (GSPE) on developing hepatic fibrosis that was induced by thioacetamide (TAA) in mice. Administration of TAA for 9 weeks led to a serious necrosis and apoptosis of the parenchymal cells, which resulted in an accumulation of excessive collagen in the liver and an increase of transformed hepatic stellate cells (HSCs). In addition, the mRNA expression of transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA), as the marker of the activated HSCs, and α1-(I)-collagen were all up-regulated significantly when compared with the control. However, combined oral administration of GSPE at 100 mg/kg suppressed the mRNA expression of TGF-β1 and α-SMA, with decreased collagen accumulation as demonstrated by histomorphological evaluation and quantitative RT-PCR. The mRNA expression of the pro-inflammatory factors, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), was remarkably enhanced by TAA treatment. However, their levels displayed a down-regulated trend beyond simultaneous GSPE treatment. Moreover, GSPE administration markedly suppressed lipid peroxidation. In conclusion, as a plant antioxidant, GSPE manifested effective hepatocellular protective action to ameliorate the developing liver fibrosis induced by chronic TAA administration in mice.
authors.affiliation: MOE Key Laboratory of Molecular Animal Nutrition and Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Yuling
authors.initials: Y
authors.lastname: Mi
authors.forename: Hongcui
authors.initials: H
authors.lastname: Cao
authors.forename: Caiqiao
authors.initials: C
authors.lastname: Zhang
authors.forename: Lanjuan
authors.initials: L
authors.lastname: Li
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D051546:Cyclooxygenase 2 / Q000235:genetics; D019610:Cytoprotection; D005260:Female; D005786:Gene Expression Regulation; D056604:Grape Seed Extract / Q000494:pharmacology*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008813:Mice, Inbred ICR; D009336:Necrosis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D044945:Proanthocyanidins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013853:Thioacetamide; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D000199:Actins; D000975:Antioxidants; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D018836:Inflammation Mediators; D044945:Proanthocyanidins; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D013853:Thioacetamide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase