Selective inhibitory effect of organophosphates on UDP-glucuronyl transferase activities in rat liver microsomes.
The effects of acute and subacute administration of diisopropylfluorophosphate (DFP) and acute administration of Soman, Sarin and Tabun on UDP-glucuronyltransferase (GT) activity towards 4-nitrophenol, 4-methylumbelliferone, phenolphthalein and testosterone in rat liver microsomes were investigated. Twenty-four hours after a single injection of DFP, the activity of GT towards 4-nitrophenol and 4-methylumbelliferone was inhibited, and the inhibitory effect continued for 3 days. The activity had recovered by 7 days after injection. The activity of GT towards phenolphthalein and testosterone was not affected at any time after injection. Soman, Sarin and Tabun showed the same effect as DFP after a single injection. After daily DFP injections, the activity of GT towards 4-nitrophenol and 4-methylumbelliferone was decreased to the same level as found following acute treatment with DFP. The in vitro addition of DFP to liver microsomes did not affect GT activity towards 4-nitrophenol. It is suggested that these changes are not due to a direct effect of DFP. Furthermore, the effects of two enzyme inducers on GT activity in the presence and absence of DFP were investigated. In the 3-methylcholanthrene (MC) pretreatment group, DFP inhibited only the GT activity towards 4-nitrophenol and 4-methylumbelliferone. On the other hand, in the phenobarbital (PB) pretreatment group, DFP did not inhibit the GT activity towards 4-nitrophenol and 4-methylumbelliferone. It was also demonstrated that MC pretreatment increased the mortality in the DFP-treated rats but that PB pretreatment suppressed it. These results suggest that DFP and other organophosphorus agents may be useful agents for studies on the heterogeneity of GT.
Watanabe
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Hoskins
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Ho
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D000738:Androsterone / Q000378:metabolism; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002802:Cholinesterases / Q000378:metabolism; D004790:Enzyme Induction; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D006923:Hymecromone / Q000378:metabolism; D007531:Isoflurophate / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D009596:Nitrophenols / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D020113:Phenolphthalein; D010635:Phenolphthaleins / Q000378:metabolism; D051381:Rats; D013739:Testosterone / Q000378:metabolism
D002800:Cholinesterase Inhibitors; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D010635:Phenolphthaleins; D007531:Isoflurophate; D006923:Hymecromone; D013739:Testosterone; D020113:Phenolphthalein; D000738:Androsterone; D014453:Glucuronosyltransferase; D002802:Cholinesterases