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• W2020951684 abstract "Intoxication of male and female mice with a single dose (300 or 600 mg/kg) of 1,1,2,2-tetrachloroethane (TTCE) resulted in significant decreases in cytochrome P-450 (to 58–73% of the control) and NADPH-cytochrome (P-450) c-reductase (to 29–35% of the control) in hepatic microsomes. This was accompanied by an alteration of mixed function monooxygenases stemming from the marked reduction (to 20–64% of the control) of several oxidative activities to selected substrates towards different P-450 isozymes (classes IA1, IA2, IIB1, IIE1 and IIIA). As phase II markers, epoxide hydrolase (≈35% loss), UDP-glucuronosyl transferase (≈42% loss) and to a lesser extent glutathione S-transferase (≈17% loss) were all affected. Also, the activity of δ-aminolevulinic (ALA) synthetase was decreased (≈57% of the control). On the contrary, heme oxygenase activity was increased (up to 35%) at the maximal dose tested. The decrease of P-450-function may be explained in terms of an alteration in the rate of heme biosynthesis and degradation, provoking a loss of heme content (≈33%) as well as of the direct inactivation of both P-450 and reductase. Because of increasing evidence on the involvement of free radical intermediates in the case of toxicity of haloalkanes, electron spin resonance spectroscopy (ESR) spin-trapping in vivo techniques were used to characterize the possible free radical species involved in the observed liver damage. The results obtained with the spin-trap N-benzylidene-2-methylpropylamine N-oxide (phenyl t-butylnitrone, PBN) provide evidence for the formation and trapping of the CHCl2CHCl free radicals. The detection of conjugated diene signals by means of second-derivative spectrophotometry, have enabled us to show that in vivo lipid peroxidation may be one of the main mechanisms responsible for TTCE hepatotoxicity." @default.
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• W2020951684 date "1992-01-01" @default.
• W2020951684 modified "2023-10-04" @default.
• W2020951684 title "On the hepatotoxicity of 1,1,2,2-tetrachloroethane" @default.
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• W2020951684 doi "https://doi.org/10.1016/0300-483x(92)90174-d" @default.
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