Genistein modulates the expression of NF-κB and MAPK (p-38 and ERK1/2), thereby attenuating d-Galactosamine induced fulminant hepatic failure in Wistar rats

Toxicol Appl Pharmacol. 2015 Mar 1;283(2):139-46. doi: 10.1016/j.taap.2015.01.012. Epub 2015 Jan 22.


Genistein is an isoflavanoid abundantly found in soy. It has been found to play an important role in the prevention of various chronic diseases including cancer. In this study, we evaluated potential therapeutic properties of Genistein against d-Galactosamine (d-GalN) induced inflammation and hepatotoxicity in male Wistar rats. Fulminant hepatic failure (FHF) was induced in rats by intraperitoneal injection of d-GalN (700mg/kgBW). Genistein (5mg/kgBW/day) was given as pre-treatment for 30days via intra-gastric route followed by d-GalN (700mg/kgBW) injection. The hepatoprotective and curative effects of Genistein were evident from a significant decrease in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as prevention of histological damage by pre-treatment of Genistein. Genistein pre-treatment significantly inhibited the increased protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), thereby reducing nitric oxide (NO) and prostaglandin-E2 (PGE) levels, respectively. In addition Genistein significantly suppressed the production of d-GalN-induced proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. These inhibitory effects were associated with the suppression of nuclear factor-kappa B (NF-ĸB) activation, IKKα/β and Mitogen activated protein kinase (MAPK) phosphorylation by Genistein in d-GalN-treated animals. In conclusion, our results suggest that Genistein may serve as a potential supplement in the prevention of hepatic and inflammatory diseases. Furthermore Genistein is able to maintain the redox potential and strengthens the antioxidant defense system of a cell.

Keywords: Antioxidant; Apoptosis; Liver damage; Necrosis; Oxidative stress; Phytoestrogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Galactosamine / toxicity*
  • Gene Expression Regulation
  • Genistein / pharmacology
  • Genistein / therapeutic use*
  • Liver Failure, Acute / chemically induced
  • Liver Failure, Acute / metabolism*
  • Liver Failure, Acute / prevention & control
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Male
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / biosynthesis*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / biosynthesis*


  • NF-kappa B
  • Galactosamine
  • Genistein
  • p38 Mitogen-Activated Protein Kinases