18-β Glycyrrhetinic acid alleviates 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats: Role in hyperproliferation, inflammation and oxidative stress

Hum Exp Toxicol. 2015 Jun;34(6):628-41. doi: 10.1177/0960327114554045. Epub 2014 Oct 28.

Abstract

2-Acetylaminofluorene (2-AAF) is a known hepatic carcinogen which leads to tumour formation in rodents. 18-β Glycyrrhetinic acid (18β-GA) derived from liquorice plant has various pharmacological properties such as anti-ulcer, anti-inflammatory, antiviral, hepatoprotective and antioxidant. This study is designed to elucidate the chemopreventive properties of 18β-GA against 2-AAF-induced liver toxicity in Wistar rats and evaluated its effect on inflammatory and tumour promotion marker and activities of different oxidative stress enzymes. Administration of 2-AAF at the dose of (50 mg/kg body weight (b.w.) intraperitoneally (i.p.)) for five consecutive days induces hepatic toxicity, inflammation, oxidative stress and hyperproliferation. Pretreatment with 18β-GA at two different doses (45 and 75 mg kg(-1) b.w.) significantly ameliorates 2-AAF-induced increased lipid peroxidation, alanine transaminase and aspartate transaminase, xanthine oxidase activities and activities of phase-II detoxifying enzymes along with the levels of glutathione content. Administration of 18β-GA also significantly restored the expressions of proliferating cell nuclear antigen, cyclooxygenase 2, inducible nitric oxide synthase and nuclear factor κB. Furthermore, histological observations also support the preventive effects of 18β-GA. Our findings suggest that pretreatment with 18β-GA showed potential hepatoprotective effects via attenuation of oxidative stress, inflammation and hyperproliferation.

Keywords: 18β-GA; 2-AAF; Hepatotoxicity; inflammation; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Acetylaminofluorene / toxicity
  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Catalase / metabolism
  • Cell Proliferation / drug effects
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Cyclooxygenase 2 / metabolism
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Transferase / metabolism
  • Glycyrrhetinic Acid / pharmacology
  • Glycyrrhetinic Acid / therapeutic use*
  • Inflammation / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress / physiology
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Rats, Wistar
  • Xanthine Oxidase / metabolism

Substances

  • NF-kappa B
  • Proliferating Cell Nuclear Antigen
  • Protective Agents
  • 2-Acetylaminofluorene
  • Catalase
  • Glutathione Peroxidase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Xanthine Oxidase
  • Glutathione Transferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione
  • Glycyrrhetinic Acid