The effect of modulation of glutathione levels on markers for aflatoxin B1-induced cell damage

Afr J Med Med Sci. 2005 Mar;34(1):37-43.

Abstract

The modulatory effect of glutathione levels on markers for aflatoxin B1 (AFB1)-induced cell damage has been investigated in the rat (susceptible specie) and the (mouse resistant specie). The concentration of GSH was depleted and increased by administering paracetamol (PAM) and cysteine respectively and activities ofglutathione S-transferase (GST) and gamma-glutamyl transpeptidase (gamma-GT) were determined. The effect ofAFB1 on hepatic lipid peroxidation in both species was also investigated. Treatment of rats with 2 mg/kg.bwt AFB1 intraperitoneally caused a depletion of GSH in the liver to a minimum at 6 h (80% of the control value) and the level returned to normal after 24 h. GST was similarly increased to a maximum at 6 h and the level also returned to normal after 24 h. GSH and GST activities were not significantly affected in AFB1-treated mice. Orally administered PAM (400 mg/kg.bwt) caused a depletion of GSH with a minimum at 6 h (59% and 36% of the control rats and mice respectively). Pretreatment of AFB1 with PAM produced a serious depletion at 6 h (34% and 35% of the control rats and mice respectively). GST activities were also marginally increased in both animals. AFB1 pretreatment mediated (P < 0.001) hepatic lipid peroxidation in rats but not in mice as assessed by the formation of thiobarbituric acid reactive substances (TBARS). Treatment of rats and mice with oral cysteine (50 mg/kg bwt) elicited a significant elevation of GSH. Administration of cysteine with AFB to rats attenuated the toxic effects of AFB1 on GSH and inhibited the formation of TBARS. gamma-GT activity was significantly increased when AFB1 alone was administered to rats but was not increased (P > 0.05) when cysteine was pretreated alone with AFB1. Combined treatment of AFB, and PAM induced 177% increase in gamma-GT activity. Overall, our results suggest that the metabolism of aflatoxin B, by GSH does not lead to the formation of toxic products but rather GSH plays a protective role in AFB1-induced cell damage and GSH pathway is less utilised in mice.

MeSH terms

  • Acetaminophen / pharmacokinetics
  • Aflatoxin B1 / adverse effects*
  • Aflatoxin B1 / pharmacokinetics
  • Animals
  • Biomarkers
  • Glutathione / pharmacology*
  • Glutathione Transferase / pharmacology*
  • Lipid Peroxidation / drug effects
  • Liver / cytology
  • Liver / drug effects*
  • Liver / enzymology
  • Liver Neoplasms, Experimental / enzymology
  • Male
  • Mice
  • Rats

Substances

  • Biomarkers
  • Acetaminophen
  • Aflatoxin B1
  • Glutathione Transferase
  • Glutathione