Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phenethyl isothiocyanate (PEITC), a constituent of cruciferous vegetables, has been shown to inhibit chemical carcinogenesis, possibly due to its ability to block the activation or to enhance the detoxification of chemical carcinogens. The present study was conducted to elucidate the biochemical mechanisms involved by characterizing the effects of PEITC on phase I and phase II xenobiotic-metabolizing enzymes. A single dose of PEITC to F344 rats (1 mmol/kg) decreased the liver N-nitrosodimethylamine demethylase (NDMAd) activity (mainly due to P450 2E1) by 80% at 2 h and the activity of NDMAd remained decreased by 40% at 48 h after treatment. The liver pentoxyresorufin O-dealkylase (PROD) activity and P450 2B1 protein level were elevated 10- and 7-fold at 24 h after treatment respectively. The liver microsomal ethoxyresorufin O-dealkylase (EROD) (mainly due to P450 1A) and erythromycin N-demethylase (mainly due to P450 3A) activities were decreased at 2-12 h after treatment and recovered afterwards. The lung microsomal PROD and EROD activities were not significantly affected; whereas, the nasal microsomal PROD and EROD activities were decreased by 40-50%. After a treatment with PEITC, the rates of oxidative metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were decreased in liver microsomes by 40-60% at 2 h and recovered gradually; the rates in lung microsomes were markedly decreased by 60-70% at 2 h and remained at the decreased level at 24 h; and the rates in nasal mucosa microsomes were decreased gradually with the lowest activities observed at 18 h (50%) followed by a gradual recovery. Furthermore, the treatment with PEITC resulted in a maximal 5-fold increase of NAD(P)H:quinone oxidoreductase and 1.5-fold increase of glutathione S-transferase activities in the liver, but the activities of these two enzymes were not significantly affected in the lung and nasal mucosa. The sulfotransferase activity in the liver was decreased by 32-48% at 24-48 h after treatment; the nasal activity was increased by 1.8- to 2.5-fold, but the lung activity was not significantly changed. The hepatic UDP glucuronosyltransferase activity was slightly decreased at 2 h but slightly increased at 48 h after treatment, but no changes were observed for the lung and nasal activities. The study demonstrates that PEITC selectively affects xenobiotic-metabolizing enzymes in the liver, lung and nasal mucosa and it is especially effective in inhibiting the P450-dependent oxidation of NNK in the lung and of NDMA in the liver.
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PMID:Effects of phenethyl isothiocyanate, a carcinogenesis inhibitor, on xenobiotic-metabolizing enzymes and nitrosamine metabolism in rats. 147 25

Three indole antioxidants were compared for their efficacy to inhibit lipid peroxidation, prevent chemical hepatotoxicity and induce enzyme systems involved in the biotransformation of xenobiotics. The dietary indolyl compound indole-3-carbinol (I-3-C), and the synthetic compounds 5,10-dihydroindeno[1,2-b]-indole (DHII) and 4b,5,9b,10-tetrahydroindeno[1,2-b]indole (THII) inhibited carbon tetrachloride (CCl4)-initiated lipid peroxidation in rat-liver microsomes, with the order of efficacy THII greater than DHII = butylated hydroxytoluene (BHT) much greater than I-3-C. Each of the indole compounds protected isolated rat hepatocytes against toxicity by CCl4, N-methyl-N'-nitro-N-nitrosoguanidine and methylmethanesulphonate (THII congruent to DHII much greater than I-3-C). In vivo administration of the indole compounds 1 hr before treatment with CCl4 protected against hepatotoxicity (THII greater than DHII greater than I-3-C). For the enzyme induction studies, phenobarbital and beta-naphthoflavone were used as standards, with corn-oil vehicle controls. The compounds were administered by gavage at 50 mg/kg body weight/day for 10 days. I-3-C produced increases in levels of hepatic cytochromes P-450 and ethoxyresorufin O-deethylase (EROD) activity, as well as in UDP-glucuronosyl transferase (UDPGT), glutathione S-transferase (GST), glutathione reductase (GSSG-Red) and quinone reductase. I-3-C produced decreased glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. DHII produced increases in EROD, UDPGT, GST, GSSG-Red and quinone reductase, with decreases in NDMA-demethylase and GSH-Px activities. The only observed effect of THII was a modest induction of EROD activity. After treatment with the indole compounds for 10 days, I-3-C enhanced, while DHII diminished, CCl4-mediated 24-hr hepatotoxicity in rats. We conclude that DHII and THII are suitable candidates to develop further as potential chemoprotective and therapeutic agents for use in humans to treat disorders involving free radicals. THII has the greater radical scavenging efficacy, whereas DHII has the greater capacity to induce many different antioxidative enzymes.
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PMID:Chemoprotective and hepatic enzyme induction properties of indole and indenoindole antioxidants in rats. 187 67