Involvement of some low-molecular thiols in the peroxidative mechanisms of lead and ethanol action on rat liver and kidney

Toxicology. 2006 Feb 15;219(1-3):11-21. doi: 10.1016/j.tox.2005.10.022. Epub 2005 Dec 2.

Abstract

The involvement of low-molecular thiols, such as reduced glutathione (GSH) and metallothionein (Mt), in the mechanisms of the peroxidative action of lead (Pb) and ethanol (EtOH) in liver and kidney was investigated on rats treated with 500 mg Pb/l (in drinking water) and 5 g EtOH/kg body wt./24h (p.o.), alone and in conjunction with each other for 12 weeks. Beside of GSH and Mt, concentration of total and non-protein SH groups (TSH and NPSH, respectively) in these organs as well as the blood activity of dehydratase of delta-aminolevulinic acid (delta-ALAD) and the urinary concentration of delta-aminolevulinic acid (delta-ALA) were determined. The exposure to Pb and EtOH alone and in conjunction with each other led to a decrease in the blood delta-ALAD activity and an increase in the urinary delta-ALA concentration, and these effects were more markedly advanced at co-exposure. In the liver and kidney of rats treated with Pb and/or EtOH, a decrease in concentrations of GSH and NPSH was noted, compared to control. However, in the Pb+EtOH group, only the liver concentrations of NPSH and GSH were lower also compared to the Pb and EtOH groups. The liver concentration of TSH decreased in the rats exposed to EtOH alone and in conjunction with Pb, whereas the kidney concentration of TSH decreased only at co-exposure to Pb and EtOH. Mt concentration was unchanged except for an increase in the liver in the Pb and Pb+EtOH groups. Two-way analysis of variance (ANOVA/MANOVA) revealed that the changes noted at the co-exposure to Pb and EtOH resulted from an independent action of the two xenobiotics as well as from their interactive action. Negative correlations noted between the liver and kidney concentrations of GSH and/or NPSH and recently reported malondialdehyde (MDA, an indicator of lipid peroxidation) concentration in both organs of those rats indicate the relationship between the content of SH groups and the intensity of the Pb and/or EtOH-induced lipid peroxidation. The results allow for the conclusion that the decrease in the liver and kidney concentrations of GSH and NPSH are involved in the mechanisms of the peroxidative action of Pb and EtOH alone and at co-exposure in these organs.

MeSH terms

  • Aminolevulinic Acid / metabolism
  • Aminolevulinic Acid / urine
  • Animals
  • Central Nervous System Depressants / toxicity*
  • Ethanol / toxicity*
  • Glutathione / metabolism
  • Kidney / drug effects
  • Kidney / metabolism*
  • Lead / toxicity*
  • Lipid Peroxidation / drug effects*
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Metallothionein / metabolism
  • Oxidative Stress / drug effects*
  • Porphobilinogen Synthase / metabolism
  • Porphobilinogen Synthase / urine
  • Rats
  • Rats, Wistar
  • Sulfhydryl Compounds / physiology*

Substances

  • Central Nervous System Depressants
  • Sulfhydryl Compounds
  • Lead
  • Ethanol
  • Aminolevulinic Acid
  • Metallothionein
  • Porphobilinogen Synthase
  • Glutathione