Induction of paracetamol biotransformation in the rat liver by gamma-hexachlorocyclohexane.
The effect of the insecticide gamma-hexachlorocyclohexane (lindane), a compound which induces the synthesis of hepatic microsomal enzymes, on the metabolism of paracetamol was investigated in the isolated perfused rat liver.
Male Wistar rats were treated with gamma-hexachlorocyclohexane (200,400 and 800 ppm) in the drinking water for 2 weeks.
When 1.0 mM paracetamol was recirculated in liver perfusion experiments (volume=140 ml ; flow=34 ml/min), the initial rate of uptake increased from 270 nmol min-1 g-1 (control) to 435 nmol min-1 g-1 (200 ppm), 575 nmol nmol min-1 g-1 (400 ppm) and 648 nmol min-1 g-1 (800 ppm).
The increased rates of uptake of paracetamol in livers from rats treated with gamma-hexachlorocyclohexane were probably due to the activation of mixed function oxidases.
The mixed function oxidases are believed to be responsible for the formation of the toxic intermediate of paracetamol metabolism, which produces necrosis of the hepatic tissue.
In consequence, one can expect that humans, chronically exposed to gamma-hexachloro-cyclohexane or similar insecticides and pesticides, are much more susceptible to liver damage when using paracetamol as a pain reliever.
Mots-clés Pascal : Pesticide, Insecticide, Inducteur enzyme, Brésil, Amérique du Sud, Amérique, Foie, Microsome, Drug-metabolizing enzyme, Enzyme, Paracétamol, Analgésique, Interaction toxique médicament, Rat, Rodentia, Mammalia, Vertebrata, Animal, Exposition professionnelle, Médecine travail, Homme, Toxicité, Organochloré, Foie pathologie, Appareil digestif pathologie, Lindane
Mots-clés Pascal anglais : Pesticides, Insecticide, Enzyme inducer, Brazil, South America, America, Liver, Microsome, Drug-metabolizing enzyme, Enzyme, Analgesic, Drug poison interaction, Rat, Rodentia, Mammalia, Vertebrata, Animal, Occupational exposure, Occupational medicine, Human, Toxicity, Organochlorine compounds, Hepatic disease, Digestive diseases, Lindane
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Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 96-0104208
Code Inist : 002B02U04. Création : 199608.