The contribution of 2,3,5-trichlorophenyl methyl sulfone, a metabolite of 1,2,4-trichlorobenzene, to the delta-aminolevulinic acid synthetase induction by 1,2,4-trichlorobenzene in rat liver.
In the present study, we investigated the contribution of methylsulfonyl metabolite derived from 1,2,4-trichlorobenzene (1,2,4-TCB) on the delta-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 i.p. 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 micromol/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.
Kato
Y
Y
School of Pharmaceutical Sciences, University of Shizuoka, Japan. kato@ys7.u-shizuoka-ken.ac.jp
Kimura
R
R
D000624:5-Aminolevulinate Synthetase / Q000187:drug effects / Q000494:pharmacology*; D000818:Animals; D002722:Chlorobenzenes / Q000009:adverse effects* / Q000378:metabolism* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology*; D007263:Infusions, Parenteral; D008099:Liver / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013450:Sulfones / Q000009:adverse effects*
D002722:Chlorobenzenes; D013450:Sulfones; C009947:1,2,4-trichlorobenzene; C083522:2,3,5-trichlorophenyl methyl sulfone; D003577:Cytochrome P-450 Enzyme System; D000624:5-Aminolevulinate Synthetase