DUAL EFFECTS OF TETRACHLORVINPHOS ON PROCAINE TOXICITY AND PROCAINESTERASE ACTIVITY IN RATS
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概要
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The effect of tetrachlorvinphos (TCVP) on liver procainesterase (PROCase) and procaine toxicity was studied in rats. TCVP is an organophosphate with an inducible effect on drug metabolizing enzymes. A single oral dose of 500 mg/kg of TCVP caused a remarkable decrease in PROCase (40% of control) 24 hr later and increased the motality after injection of procaine (250 mg/kg, i.p.) from 54% to 87%. Conversely, it was observed that PROCase elevated to 140% of the control and mortality decreased from 54% to 25% on day 3. With repeated administration of TCVP (500 mg/kg/day) for 5 days, the PROCase activity that was inhibited on day 1 was gradually restored to normal levels by 5 days and the mortality alterd to 25%. The inducible effect on PROCase was examined using desmethyl-TCVP, a metabolite of TCVP without inhibitory effect on the enzyme; PROCase activity was enhanced to 1.6-fold of the control and procaine concentration in the brain was reduced to 30% of the control, accompanied with no death of rats after procaine injection. Electrophoresis of the solubilized liver microsomal fraction confirmed the inducible effect of TCVP on PROCase; microsomal protein from the TCVP-treated rat was more deeply stained than that from the control, and the PROCase activity of two anodic bands increased in the TCVP-treated microsomes. These results indicate that TCVP has a dual action on PROCase, inducible and inhibitory, and that the direct inhibitory effect of TCVP might mask the increased amount of the enzyme induced by repeated administration of TCVP. The dual effect of TCVP on PROCase would cause the change in procaine toxicity.
- 社団法人 日本薬理学会の論文
著者
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Moroi Kayoko
Department Of Experimental Pharmacology Research Institute For Chemobiodynamics Chiba University
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Kuga Tetsuro
Department Of Experimental Pharmacology Research Institute For Chemobiodynamics Chiba University
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