title: Bee venom inhibits hepatic fibrosis through suppression of pro-fibrogenic cytokine expression.
abstract: Bee venom (BV) has a long tradition of use for the control of pain and inflammation in various chronic diseases. Carbon tetrachloride (CCl4) is known to induce hepatotoxicity after being metabolized to the highly reactive trichloromethyl free radical and its peroxy radical. The purpose of the current study was to examine whether BV regulates the pro-inflammation and fibrosis related genes against a mouse model of hepatic fibrosis induced by CCl4 and ethanol-treated hepatocytes (ETH). Test mice were administered with CCl4 (2 ml/mg) and hepatocytes were treated with 25 mM ethanol. BV was added to the final concentration of 0.05-0.5 mg/kg and 1-100 ng/ml for in vivo and in vitro testing, respectively. Fibrotic livers and ETH were used for the measurement of hepatocyte necrosis, pro-inflammatory cytokines and fibrogenic genes. BV suppressed CCl4-induced hepatocyte necrosis markers of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). It also inhibited the secretion of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Moreover, BV inhibited CCl4-induced expression of transforming growth factor (TGF)-beta1, alpha-smooth muscle actin (SMA) and fibronectin. Similarly, ETH exhibited significant suppression of IL-1beta, TNF-alpha, TGF-beta1 and fibronectin when cultured with BV. These results suggest that BV possesses anti-fibrogenic properties that are mediated by the suppression of pro-inflammatory cytokines and fibrogenic gene expression. BV has substantial therapeutic potential for the treatment of fibrotic diseases.
authors.affiliation: Department of Pathology, Catholic University of Daegu, College of Medicine, Daegu 705-718, Korea.
authors.forename: Soo-Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Kim
authors.forename: Woo-Ram
authors.initials: WR
authors.lastname: Lee
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
authors.forename: Kwang-Gill
authors.initials: KG
authors.lastname: Lee
authors.forename: Sang-Mi
authors.initials: SM
authors.lastname: Han
authors.forename: Joo-Hong
authors.initials: JH
authors.lastname: Yeo
authors.forename: Sok Cheon
authors.initials: SC
authors.lastname: Pak
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D056705:Apitherapy; D001219:Aspartate Aminotransferases / Q000097:blood; D001514:Bee Venoms / Q000494:pharmacology / Q000627:therapeutic use*; D002251:Carbon Tetrachloride; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism / Q000517:prevention & control*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D001514:Bee Venoms; D016207:Cytokines; D005353:Fibronectins; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C544013:alpha-smooth muscle actin, mouse; D000431:Ethanol; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase