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  • The contribution of 2,3,5-trichlorophenyl methyl sulfone (cas 104380-10-1), a metabolite of 1,2,4-trichlorobenzene, to the δ-aminolevulinic acid synthetase induction by 1,2,4-trichlorobenzene in rat liver
  • Add time:08/10/2019         Source:sciencedirect.com

    In the present study, we investigated the contribution of methylsulfonyl metabolite derived from 1,2,4-trichlorobenzene (1,2,4-TCB) on the δ-aminolevulinic acid (ALA) synthetase induction by the parent compound in rats. The time courses of increasing of hepatic microsomal total cytochrome P450 content after a single ip administration of 1,2,4-TCB (1.36 mmol/kg), and 2,3,5- and 2,4,5-trichlorophenyl methyl sulfones (2,3,5- and 2,4,5-TCPSO2Mes) (50 μmol/kg each) were in parallel with those of increasing of the total heme content in liver microsomes. 1,2,4-TCB significantly increased the heme oxygenase activity, but 2,3,5- and 2,4,5-TCPSO2Mes did not. On the other hand, 1,2,4-TCB and 2,3,5-TCPSO2Me markedly enhanced the ALA synthetase activity. No change was observed in this enzyme activity after the administration of 2,4,5-TCPSO2Me. After the administration of 1,2,4-TCB to the rats treated with dl-buthionine-(S,R)-sulfoximine (BSO) and to the non-BSO-treated rats, the concentrations of both 2,3,5- and 2,4,5-TCPSO2Mes were significantly lower in liver of the BSO-treated rats than in liver of the non-BSO-treated rats. Additionally, the 1,2,4-TCB did not elevate the ALA synthetase activity in the BSO-treated rats. On the other hand, the administration of 2,3,5-TCPSO2Me to BSO-treated rats resulted in induction of ALA synthetase. The results strongly suggest that the methyl sulfone derived from 1,2,4-TCB, i.e., 2,3,5-TCPSO2Me, contributes highly to the induction of the ALA synthetase activity by the parent compound.

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