title: Combination therapy with taurine, epigallocatechin gallate and genistein for protection against hepatic fibrosis induced by alcohol in rats.
abstract: This study was to investigate the possibility of enhancing the anti-fibrotic effect by using a combination therapy with taurine, epigallocatechin gallate and genistein in a rat liver fibrosis model induced by alcohol, and to explore its underlying mechanism. Hepatic fibrosis was induced by intragastric administration with various amount of alcohol (5.0-9.5 g/kg) within 24 weeks in rats. The model group received alcohol only, and treatment groups received the corresponding drugs plus alcohol respectively, while the normal control group received an equal volume of saline. The antifibrotic effects of combination therapy were assessed directly by hepatic histology, and indirectly by measurement of serum biochemical markers, the fibrosis markers and related key cytokines/proteins. The results showed that combination therapy could significantly improve the liver function, as indicated by decreasing levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyltransferase, interleukin-6 and tumor necrosis factor-α. Moreover, combination therapy could effectively suppress the serum levels of fibrosis markers and hepatic hydroxyproline content, inhibit collagen deposition and reduce the pathological tissue damage. Research on mechanism showed that combination therapy was able to markedly reduce lipid peroxidation and recruit the anti-oxidative defense system, and inhibit the expression of B-cell lymphoma 2, α-smooth muscle actin, transforming growth factor β(1) and small mothers against decapentaplegic homolog 3 proteins. Our results showed that combination therapy is effective in attenuating hepatic injury and fibrosis in the alcohol-induced rat model. The improved efficacy of the combination therapy with its good safety profile could represent a new protective approach for liver fibrosis.
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Zhuo
authors.forename: Ming
authors.initials: M
authors.lastname: Liao
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.forename: Quanfang
authors.initials: Q
authors.lastname: Huang
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.forename: Renbin
authors.initials: R
authors.lastname: Huang
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.forename: Xing
authors.initials: X
authors.lastname: Lin
mesh_terms: D000199:Actins / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001219:Aspartate Aminotransferases / Q000097:blood; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D000431:Ethanol / Q000009:adverse effects; D019833:Genistein / Q000008:administration & dosage*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000097:blood; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D051900:Smad3 Protein / Q000378:metabolism; D013654:Taurine / Q000008:administration & dosage*; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000199:Actins; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D002392:Catechin; D016207:Cytokines; D000431:Ethanol; D019833:Genistein; D009195:Peroxidase; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051900:Smad3 Protein; D013654:Taurine; D005723:gamma-Glutamyltransferase; C497787:Smad3 protein, rat; C498862:Acta2 protein, rat; C045651:epigallocatechin gallate