Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of m- and o-dichlorobenzenes (DCBs), 1,2,4-trichlorobenzene (TCB) and their methylsulfonyl metabolites on the activities of hepatic microsomal reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase, reduced nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase and uridine diphosphate (UDP)-glucuronyltransferase (UDPGT) were studied. The treatment of rats with m-DCB, 1,2,4-TCB, 2,4-, 3,5- or 3,4-dichlorophenyl methyl sulfone (DCPSO2Me) or 2,4,5-trichlorophenyl methyl sulfone (TCPSO2Me) significantly increased NADPH-cytochrome c reductase activity, but o-DCB had no effect on this enzyme activity. All three chlorinated benzenes slightly reduced NADH-cytochrome b5 reductase activity, whereas the methylsulfonyl compounds elicited no change in the enzyme activity. Treatments with m- and o-DCBs, 1,2,4-TCB and 2,4,5-TCPSO2Me enhanced UDPGT activities toward both chloramphenicol (CP) and p-nitrophenol (NP). 2,4-, 3,5- and 3,4-DCPSO2Mes increased the activity of UDPGT toward CP but not toward p-NP. These findings concerning the effects of 2,4-, 3,5- and 3,4-DCPSO2Mes on the activities of NADPH-cytochrome c reductase and UDPGT support our hypothesis that the methylsulfonyl metabolites derived from m- and o-DCBs are phenobarbital-type inducers of the hepatic microsomal drug-metabolizing enzymes. It is concluded that the methyl sulfone derivatives of m- and o-DCBs and 1,2,4-TCB are inducers of phase I reactions in hepatic microsomal drug metabolism, and they have increasing effects on the phase II enzyme activities, such as UDPGT. Thus, the methyl sulfones seem to play an important role in the inducing effects of their parent compounds, m- and o-DCBs and 1,2,4-TCB, on the drug-metabolizing enzyme systems.
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PMID:Effects of chlorobenzenes and their methyl sulfone metabolites on microsomal enzymes associated with drug metabolism in rat liver. 314 7

1. The effects of feeding allyl sulphides to rat (2000 ppm of the diet for 15 days) were investigated on various microsomal hepatic drug-metabolizing enzymes by their immunochemical detection and catalytic activity. 2. Allyl sulphides provoked a temporary dietary restriction, which enhanced the microsomal level of P450 and the activities of NADH-cytochrome c reductase and p-hydroxybiphenyl UDP-glucuronyltransferase (UDPGT 2), and lowered the activities of p-nitrophenol hydroxylase (PNPH), N-nitrosodimethylamine demethylase (NDMAD), laurate omega-hydroxylase (LAH) and glutathione S-transferase (GST). Therefore, pair-fed animals were used as a more relevant control for the dietary effects of allyl sulphides. 3. Diallyl sulphide (DAS) as well as diallyl disulphide (DADS) produced an enhancement of the microsomal level of P4501A2, 2B1/2 and 3A1/2, and epoxide hydrolase (EH) proteins, with an increase in the enzymatic activities they catalyse: ethoxyresorufin O-deethylase (EROD), aryl hydrocarbon hydroxylase (AHH), methoxyresorufin O-demethylase (MROD), ethoxycoumarin O-deethylase (ECOD), pentoxyresorufin O-depentylase (PROD), benzoxyresorufin O-debenzylase (BROD) and EH. Although P4502E1 proteins were lowered on treatment, NDMAD activity was not modified, and PNPH activity was even enhanced by allyl sulphides. Only DAS treatment raised erythromycin N-demethylase (ERDM) activity. 4. Both DAS and DADS increased the activity of GST and p-nitrophenol UDP-glucuronyltransferase (UDPGT 1), whereas UDPGT 2 activity was enhanced only by DAS.
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PMID:Modification of hepatic drug-metabolizing enzymes in rat fed naturally occurring allyl sulphides. 801 91

The aim of the present study was to investigate the interaction of 2,4,6-trinitrotoluene (TNT) with liver biotransformation enzymes in European eel Anguilla anguilla (Linnaeus, 1758). Eels were exposed to 0.5, 1 and 2.5mg/l nominal concentrations of TNT for 6 and 24h. Modulation of CYP1A1, UDPGT and GST genes was investigated by real-time PCR. Total CYP450 content, NADPH cytochrome c reductase activity, CYP1A and CYP2B-like activities, such as EROD, MROD and BROD, as well as GST and UDPGT activities, were measured by biochemical assays. An in vitro study was performed on EROD in order to evaluate catalytic modulation by TNT. No modulation of the CYP1A1 gene or protein was observed in TNT-exposed eels. On the other hand, a significant decline of EROD and MROD activities was observed in vivo. An increase in NADPH cyt c reductase, and phase II enzymes (UDPGT and GST) were observed at both gene expression and activity levels. The overall results indicated that TNT is a potential competitive inhibitor of CYP1A activities. A TNT metabolic pathway involving NADPH cyt c reductase and phase II enzymes is also suggested.
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PMID:Interactions of 2,4,6-trinitrotoluene (TNT) with xenobiotic biotransformation system in European eel Anguilla anguilla (Linnaeus, 1758). 1840 54