Multiple activation of chloroform in kidney microsomes from male and female DBA/2J mice.
Microsomes from the renal cortex of DBA/2J mice can metabolize chloroform through oxidative and reductive pathways, similar to hepatic microsomes. The oxidative or reductive nature of CHCl3 activation is strictly dependent on the oxygenation of the incubation mixture, as indicated by the formation of qualitatively different adducts to phospholipids (PLs). The protein and lipid binding levels measured in kidney microsomes from control females differed significantly from the binding levels observed with kidney microsomes from male and testosterone-treated female DBA/2J mice in aerobic conditions only. Therefore, the sex-dependent CHCl3-induced acute nephrotoxicity seems related only with the oxidative CHCl3 activation. The levels of adducts to PL polar heads and to protein showed a strict correlation with each other. Therefore, the assay of adducts to PL polar heads may be used as a substitute for the assay of adducts to protein. This might be especially convenient when studying the effects of both phosgene and the trichloromethyl radicals.
Ade
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Istituto Superiore di Sanità, Biochemical Toxicology Unit, Roma, Italy.
Guastadisegni
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C
Testai
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E
Vittozzi
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L
D000818:Animals; D001711:Biotransformation; D002725:Chloroform / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000502:physiology; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008861:Microsomes / Q000378:metabolism*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology
D010743:Phospholipids; D013739:Testosterone; D002725:Chloroform; D005978:Glutathione