Chloroform interaction with chlordecone and mirex: correlation between biochemical and histological indices of toxicity and quantitative tissue levels.
The purpose of this study was to investigate whether the tissue distribution of chlordecone (CD) and mirex (M) might explain the difference in the potentiation of CHCl3 liver injury. Male Sprague-Dawley rats received either a single oral dose of CD or M (1, 2.5, 5, 10, 25, or 50 mg/kg) or three single daily doses of CD or M (0.5, 2, or 10 mg/kg). Eighteen hours following the last treatment, the animals were divided into two groups. The first group was killed and residues of CD or M in plasma, kidney, liver, and adipose tissue were measured by gas-liquid chromatography. The other group received CHCl3 (0.5 ml/kg, po) and was killed 24 hr later. Biochemical and histological indices of liver injury were evaluated. CD administered either singly or repetitively is more effective than M in potentiating the CHCl3-induced liver injury. This was exhibited by a higher increase in the plasma activities of the enzymes alanine aminotransferase and ornithine carbamoyl transferase and a greater alteration of the morphological pattern. There was a very good correlation between biochemical and histological indices. However, the severity of the liver injury did not parallel tissue concentrations. With M, a relatively poor potentiation of the liver damage was observed although adequate hepatic concentrations were present.
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism; D007631:Chlordecone / Q000493:pharmacokinetics / Q000633:toxicity*; D002725:Chloroform / Q000493:pharmacokinetics / Q000633:toxicity*; D002849:Chromatography, Gas; D004347:Drug Interactions; D007306:Insecticides / Q000633:toxicity*; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008917:Mirex / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D007306:Insecticides; D002725:Chloroform; D007631:Chlordecone; D008917:Mirex