2,3-Dimercapto-1-propanol does not alter the porphobilinogen synthase inhibition but decreases the mercury content in liver and kidney of suckling rats exposed to HgCl2

Basic Clin Pharmacol Toxicol. 2005 Apr;96(4):302-8. doi: 10.1111/j.1742-7843.2005.pto960405.x.

Abstract

Heavy metals have received great attention as environmental pollutants mainly because once introduced in the biological cycle they are incorporated in the food chain. Especially the mercury toxicity due to a diversity of effects caused by different chemical species should be emphasized. Heavy metal intoxication has been treated with chelating agents such as 2,3-dimercapto-1-propanol (BAL). However, the efficacy of this treatment is questionable due to the lack of specific effect on the toxic metal. The present study examined the effects of HgCl2 exposure (five doses of 5.0 mg/kg between ages 8 to 12 days) on physiological parameters, on porphobilinogen synthase activity, and on mercury content in liver, kidneys and brain from suckling rats. The effect of BAL (one dose of 12.5-75 mg/kg) applied 24 hr after mercury intoxication on these parameters was also investigated. The results demonstrate that HgCl2 intoxication induced a decrease of corporal weight gain as well as brain weight and an increase in renal weight. The inhibition of porphobilinogen synthase from liver and kidney, is still significant and was not modified by subsequent BAL treatment. However, BAL altered two effects induced by mercury: increase in death percentage and decrease in mercury contents in liver and kidney. The increase of mortality induced by mercury was not promoted by metal redistribution to brain nor by the increase of porphobilinogen synthase inhibition induced by metal. More investigations are necessary to determine if the different effects of BAL on intoxication by metals are possibly related to other tissues and/or if the probable metal-chelating complex formed is more toxic than the metal itself.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn / physiology
  • Brain / drug effects
  • Brain / metabolism
  • Brain Chemistry
  • Death
  • Dimercaprol / administration & dosage
  • Dimercaprol / adverse effects
  • Dimercaprol / pharmacokinetics*
  • Drug Administration Schedule
  • Drug Interactions
  • Drug Therapy, Combination
  • Female
  • Injections, Subcutaneous
  • Kidney / chemistry*
  • Kidney / drug effects
  • Kidney / metabolism
  • Liver / chemistry*
  • Liver / drug effects
  • Liver / metabolism
  • Mercuric Chloride / administration & dosage
  • Mercuric Chloride / antagonists & inhibitors
  • Mercuric Chloride / pharmacokinetics*
  • Mercury / antagonists & inhibitors*
  • Mercury / chemistry
  • Organ Size / drug effects
  • Porphobilinogen Synthase / drug effects
  • Porphobilinogen Synthase / metabolism
  • Porphobilinogen Synthase / pharmacokinetics*
  • Rats
  • Rats, Wistar
  • Weight Gain / drug effects

Substances

  • Dimercaprol
  • Mercuric Chloride
  • Porphobilinogen Synthase
  • Mercury