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Modulation of trichloroethylene in vitro metabolism by different drugs in rats

Mouna Cheikh Rouhou1, Isabelle Rheault, Sami Haddad

  • 1TOXEN, Département des Sciences Biologiques, Université du Québec à Montréal, CP 8888 Succ Centre-ville, Montreal, Canada H3C 3P8.

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|October 24, 2012
PubMed

Insights

This study investigated how common drugs interact with trichloroethylene (TCE) metabolism. Some drugs significantly alter TCE metabolites, suggesting potential impacts on toxicity in medicated individuals.

Area of Science:

  • Environmental Toxicology
  • Pharmacology
  • Drug Metabolism

Background:

  • Trichloroethylene (TCE) is a prevalent industrial solvent with significant human exposure.
  • Drug interactions can potentially alter the toxicity profile of TCE.
  • Understanding these interactions is crucial for assessing risks in co-exposed populations.

Purpose of the Study:

  • To identify and characterize metabolic interactions between TCE and 14 common drugs.
  • To investigate the impact of these interactions on TCE metabolite formation (trichloroethanol and trichloroacetate).
  • To determine the mechanisms of interaction using in vitro assays.

Main Methods:

  • Incubation of TCE with rat suspended hepatocytes in the presence of various drugs.
  • Quantification of TCE and its metabolites (TCOH, TCA) using gas chromatography-mass spectrometry (GC-MS).
  • Microsomal assays (oxidation, glucuronidation) to characterize strong interactions.

Main Results:

  • Drugs were categorized into four groups based on their effect on TCE metabolites.
  • Naproxen, salicylic acid, acetaminophen, gliclazide, and valproic acid showed the strongest interactions, altering metabolite levels by ≥50%.
  • Naproxen, gliclazide, and valproic acid confirmed interactions in microsomes, with specific inhibition patterns and constants (Ki).

Conclusions:

  • Significant metabolic interactions exist between TCE and several widely used drugs.
  • Specific drugs like naproxen, gliclazide, and valproic acid demonstrably modulate TCE metabolism.
  • Further research is needed to ascertain the clinical relevance of these findings in humans.

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