Glucose - diethyldithiocarbamate 가 흰쥐의 약물 대사 효소에 미치는 영향 = Effect of Glucose - diethyldithiocarbamate on Drug Metabolizing Enzymes in Rats

다국어 초록 (Multilingual Abstract)

The modulation of cytochrome P450(P450) activities and glutathione S-transferase (GST) was investigated after i.p. administration of glucose-diethyldithiocarbamate (Glu-DDTC) to rats. P450 1A2 and 2E1 activities were inhibited by 60% 4 hr after the administration of 200 mg Glu-DDTC/kg and those activities were recovered to original levels 24 hr after dosing. In contrast, GST activities were enhanced up to 24 hr after dosing. These results seem to be due to the bifunctional activity of Glu-DDTC. Glu-DDTC acts as an inhibitor of P450 enzymes as well as inducer of GST enzyme. Glu-DDTC inhibited PNP hydroxylation (P450 2E1) and ethoxycoumarin O-deethylation (P450 1A2) in a dose-dependent manner up to 200 mg/kg wherease it did not affect testosterone 6β-hydroxylation (P450 3A) and pentoxyresorufin O-dealkylation (P450 2B) activities. Induction of GST activity toward 1-chloro-2,4-dinitrobenzene (CDNB) and 1,2-dichloro-4-nitrobenzenen (DCNB) was dependent on the dose of Glu-DDTC and no species difference in the GST induction was seen between rat and mouse. Amoung GST subunits, Ya, Ybl and partially Yb2 were induced by Glu-DDTC as conjugated by western blotting. The levels Yp, Yk and Yc subunits were not affected by Glu-DDTC treatment. Therefore the enhanced activity of GST toward CDNB and DCNB might be due to the induction of Ya, Yb1 and partially Yb2 subunits. In conclusion, Glu-DDTC selectively inhibited P450 1A2 and P450 2E1 activities whereas it enhanced Ya, Yb1 subunits and partially Yb2 subunits of GST and the antimutagenic activity of this compound might be attributed from the modulation of these enzyme activities in animals.