Effect of glutathione (GSH) depletion on the serum levels of triiodothyronine (T3), thyroxine (T4), and T3/T4 ratio in allyl alcohol-treated male rats and possible protection with zinc

Int J Toxicol. 2001 Jan-Feb;20(1):15-20. doi: 10.1080/109158101750103332.

Abstract

The current study is an attempt to elucidate the link between glutathione (GSH) as a major endogenous antioxidant and the thyroid hormone levels. Rats were treated with a single intraperitoneal (IP) dose of either ZnCl2 (5 mg/kg) or allyl alcohol (AIAI) (1.5 mmol/kg), which acts as a GSH-depleting agent. ZnCl2 and AIAI were administered either alone (Zn- and AlAl-treated groups) or in combination (AIAI + Zn-treated group). Blood and liver samples were collected 5 hours post treatment in all groups. Zinc was used because of its potential intracellular regulatory effect as a calcium antagonist. The data indicate a decrease in the serum levels of triiodothyronine (T3) and thyroxin (T4), the T3/T4 ratio, and serum and liver total protein in AlAl-treated rats. Increases in the serum levels of aminotransferases, hepatic calcium, and lipid peroxidation products were observed. The decrease in T3 and the T3/T4 ratio indicates a reduced capacity of the microsomes to convert T4 into T3. Rats treated with AlAl + Zn had replenished hepatic GSH and showed a marked decrease in the serum levels of aminotransferases and in the liver calcium contents and lipid peroxidation products compared to AlAl-treated rats. In contrast, zinc treatment failed to normalize the serum levels of total protein, T3 and T4, and the T3/T4 ratio in the same rats. Rat treated with ZnCI2 alone tended to have a lower serum protein level that was accompanied with a significant decrease in both serum T3 and the T3/T4 ratio. The effect of zinc in increasing capillary permeability with the probable leakage of some serum proteins including the thyroid-binding proteins could possibly be the reason behind this finding. Possible covalent binding of AIAI metabolites to some cellular proteins may explain the persistence of reduced liver protein levels in zinc-protected rats.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Calcium / metabolism
  • Chemical and Drug Induced Liver Injury / blood*
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Chlorides / pharmacology*
  • Drug Interactions
  • Glutathione / deficiency*
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Propanols / toxicity*
  • Rats
  • Rats, Wistar
  • Thyroxine / blood*
  • Triiodothyronine / blood*
  • Zinc Compounds / pharmacology*

Substances

  • Chlorides
  • Propanols
  • Zinc Compounds
  • Triiodothyronine
  • allyl alcohol
  • zinc chloride
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione
  • Thyroxine
  • Calcium