title: Genistein attenuates D-GalN induced liver fibrosis/chronic liver damage in rats by blocking the TGF-β/Smad signaling pathways.
abstract: OBJECTIVE
  Genistein is a major isoflavonoid abundantly found in soy. Earlier genistein has been reported to possess protective effect against a multitude of disorders including cancer. Previously we demonstrated the protective effects of Genistein in d-Galactosamine (D-GalN) induced fulminant hepatic failure (FHF) in rats. In present study, we evaluated the hepatoprotective activity of Genistein in rat model of chronic liver damage and liver fibrosis.
  
  
  METHODS
  Liver fibrosis was induced by intraperitoneal injection of D-GalN (250 mg/kg BW) twice a week for 12 weeks. Genistein (5 mg/kg BW) was given via intra-gastric route as co-treatment daily for 12 weeks.
  
  
  RESULTS
  Genistein co-treatment significantly attenuated D-GalN-induced chronic liver damage and liver fibrosis as evident from a significant amelioration in functional impairment, including inhibition of the activation of Hepatic stellate cells (HSC), decreased expression in alpha smooth muscle actin (α-SMA) and accumulation of collagen matrix, and an elevation in serum alanine transaminase (ALT) and aspartate transaminase (AST) level. In addition Genistein co-treatment was associated with elevated expression of hepatic Smad7, which ultimately blunts the expression of TGF-β and the activation of TGF-β/Smad signaling. Furthermore Genistein significantly prevented the histopathological changes induced by D-GalN.
  
  
  CONCLUSIONS
  Our results suggest that Genistein could be a novel therapeutic/nutraceutical agent in treating chronic liver damage and liver fibrosis. In addition our study also suggests a possible mechanism of action in which Smad7-induced inhibition of TGF-β/Smad2/3 can be a central mechanism by which Genistein protects liver from chronic injury.
authors.affiliation: Department of Biotechnology, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Ajaz Ahmad
authors.initials: AA
authors.lastname: Ganai
authors.affiliation: Department of Biotechnology, Jamia Millia Islamia, New Delhi, 110025, India. Electronic address: biotechpharma2020@gmail.com.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Husain
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002908:Chronic Disease; D003094:Collagen / Q000096:biosynthesis; D005688:Galactosamine; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C002744:3-nitrotyrosine; D014443:Tyrosine; D005688:Galactosamine; D003094:Collagen; D019833:Genistein
keywords: Apoptosis; Cirrhosis; Oxidative stress; Steatohepatitis