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

Male C57Bl/6 mice were treated for 5 days with 0.05% perfluorooctanoic acid (PFOA) in their diet. This treatment resulted in a potent induction of peroxisomal fatty acid beta-oxidation in the liver. In order to investigate recovery from treatment with PFOA, mice were given normal laboratory chow for up to 20 days after termination of PFOA administration. It was established that the activities of peroxisomal lauoryl-CoA oxidase and palmitoyl-CoA oxidation were still elevated 2-3 weeks after termination of treatment. The catalase activity recovered in the cytosolic fraction was also still significantly elevated after 20 days with normal laboratory chow. Furthermore, the protein content of the mitochondrial fraction was increased by PFOA and had not returned to control level at the end of the recovery period. Perfluorooctanoic acid also caused a persistent effect in omega hydroxylation of lauric acid (cytochrome P-452). The activities of cytosolic DT-diaphorase and glutathione transferase were also enhanced by PFOA. However, these two enzymes recovered relatively rapidly from the treatment (2-20 days). This study reveals two different patterns of recovery from PFOA treatment, one involving parameters that recovered completely, or almost completely, from PFOA treatment after 20 days and another involving parameters that were still elevated at the end of the recovery period.
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PMID:Perfluorooctanoic acid has persistent effects on peroxisome proliferation and related parameters in mouse liver. 129 9

Male and female C57Bl/6 mice were administered perfluor-octanoic acid PFOA; 0.02-0.05% w/w; 5-10 days) in their diet. This treatment resulted in a several-fold induction of hepatic peroxisomal fatty acid beta-oxidation (monitored as increases in cyanide-insensitive palmitoyl-CoA oxidation, lauroyl-CoA oxidase and catalase activity) in all animals. The protein content of the hepatic mitochondrial fraction was also increased in all mice exposed to PFOA. Furthermore, studies on xenobiotic-metabolizing enzymes revealed no sex-related difference in the response to PFOA. All mice demonstrated a dramatic increase in omega-hydroxylation of lauric acid. Cytosolic epoxide hydrolase, glutathione transferase and DT-diaphorase activities were increased about 2-5-fold. These results with mice differ dramatically from previous studies and our own experiments here with Wistar rats, in which exposure to PFOA causes hepatic peroxisome proliferation in male animals, whereas females are unaffected.
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PMID:The effects of perfluoro-octanoic acid on hepatic peroxisome proliferation and related parameters show no sex-related differences in mice. 149 16

Although the mechanisms responsible for chemically induced oxidative stress are under intense investigation, little is known about the effects of prooxidant chemicals on the expression of drug-metabolizing enzymes. We examined the effects of diquat (0.1 mmol/kg, ip) and ciprofibrate (0.025% w/w, diet), chemicals which induce oxidative stress via different biochemical mechanisms, on the steady-state messenger RNA (mRNA) levels of six cytochrome P450 enzymes, seven glutathione S-transferase (GST) isoenzymes, UDP-glucuronosyl transferase 1-06 (UGT1*06), gamma-glutamylcysteine synthetase (gamma GCS), NADP(H):quinone oxidoreductase (quinone reductase), Cu/Zn superoxide dismutase (SOD), catalase, and 18S ribosomal RNA in the livers of male Sprague-Dawley rats. Effects of chemical treatments on mRNA levels were compared to changes in catalytic activities for selected enzymes. Ciprofibrate treatment selectively decreased CYP1A2 mRNA expression, whereas both chemicals suppressed CYP3A2 mRNA expression. CYP4A1 mRNA expression and lauric acid hydroxylase activities were induced by ciprofibrate treatment, whereas diquat treatment moderately increased CYP4A1 mRNA levels without affecting lauric acid hydroxylase activities. The steady-state mRNA levels encoding constitutively expressed GST isozymes (Ya1, Ya2, Yb1, Yb2, and Yc1) were decreased by diquat exposure, and the mRNA encoding four of the five constitutively expressed GSTs (Ya1, Ya2, Yb1, and Yc1) were also decreased by ciprofibrate treatment. Nonconstitutively expressed or low constitutively expressed genes (CYP1A1, CYP2B1, CYP2B2, GST Yc2, GST Yf, and UGT1*06) were not induced by exposure to the prooxidants. Changes in isozyme-specific catalytic activities were more consistent with the observed changes in mRNA expression for the GSTs than for the P450s. Both treatments had inhibitory effects on hepatic GSH biosynthesis by decreasing gamma GCS large-subunit mRNA expression, gamma GCS catalytic activities, and hepatic GSH concentrations. Cu/Zn SOD and quinone reductase mRNA levels were increased after ciprofibrate exposure, whereas Cu/Zn SOD mRNA expression was decreased in the diquat-treated animals. The results of this study indicate that diquat and ciprofibrate can decrease the expression profile of a number of phase I, phase II, and antioxidant enzymes and inhibit GSH biosynthesis. These effects may involve the pretranslational loss of hepatic mRNAs, possibly due to accelerated production of reactive oxygen species.
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PMID:The effects of diquat and ciprofibrate on mRNA expression and catalytic activities of hepatic xenobiotic metabolizing and antioxidant enzymes in rat liver. 767 60

Perfluorooctane sulfonic acid is almost as potent as perfluorooctanoic acid in causing increases in peroxisomal fatty acid beta-oxidation, peroxisomal catalase activity, omega-hydroxylation of lauric acid, cytosolic epoxide hydrolase activity and cytosolic DT-diaphorase activity. Octane sulfonic acid was ineffective at doses used for perfluorooctane sulfonic acid and perfluorooctanoic acid. The results support the theory of co-regulation of these parameters and peroxisome proliferation. The fact that perfluorooctane sulfonic acid causes peroxisome proliferation challenges the hypothesis that the first step in this process is formation of a thioester between the proliferator (the carboxylic group) and coenzyme A.
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PMID:Perfluorooctane sulfonic acid is a potent inducer of peroxisomal fatty acid beta-oxidation and other activities known to be affected by peroxisome proliferators in mouse liver. 838 58

The endocrine system of wildlife is exposed to a wide variety of natural and man-made chemicals which may lead to damage to the reproductive system and other adverse effects, including alteration of drug-metabolizing enzymes. In the present study, the effects of in vivo exposure to a natural (17beta-estradiol: E2) or a xenoestrogen (4-nonylphenol: NP) estrogen or an anti-estrogen (3,3',4,4',5-pentachlorobiphenyl: PCB 126) upon vitellogenin (VTG) synthesis and hepatic phase 1 and 2 enzymes have been investigated in adult male sea bass. By means of ELISA analysis with the use of polyclonal antibodies prepared against VTG purified from E2-treated sea bass, we assessed the time course and sensitivity of VTG induction in the plasma of sea bass treated with E2 at 0.1, 0.5, 2.5 and 5.0 mg/kg doses or NP at 5.0 or 50 mg/kg doses, respectively. Sea bass sensitivity to this induction was found to be similar to that of other fish species, but with a delay in maximal response. E2 treatment also caused a selective time- and dose-dependent inhibition of hepatic CYP1A-linked EROD and phase 2 glutathione S-transferase (GST) activities, without affecting the activity of CYP3A-linked 6beta-testosterone hydroxylase, (omega)- and (omega-1)-lauric acid hydroxylases or phase 2 DT-diaphorase. A similar selective inhibition on CYP1A was also observed in fish treated with 50 mg/kg NP. The results regarding CYP1A and CYP3A were also confirmed by Western blot analysis. When the sea bass were treated with either 10 or 100 microg/kg PCB 126, an AhR ligand not yet tested in vivo in fish to assess its anti-estrogenicity, a modest and selective induction of EROD and DT-diaphorase activities was observed. Interestingly, both these activities were recovered to their control levels in sea bass co-treated with 0.5 mg/kg E2 and 10 or 100 microg/kg PCB 126, probably through a cross-talk mechanism between the estrogen receptor and AhR or other transcription factors that regulate the expression of these enzymes. Furthermore, it was demonstrated that PCB 126 possesses a potent anti-estrogenic activity in the sea bass in vivo as it inhibited the E2-induced VTG synthesis with an IC50 of 28 microg/kg. The results of this study suggest that the exposure of fish to xenoestrogens or anti-estrogens may alter, in addition to various physiological processes, the expression of specific CYPs and phase 2 enzymes, thereby reducing the capability of their detoxication system.
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PMID:Effects of 17beta-estradiol, 4-nonylphenol and PCB 126 on the estrogenic activity and phase 1 and 2 biotransformation enzymes in male sea bass (Dicentrarchus labrax). 1621 70

This study investigated some aspects of xenobiotic metabolism in the Nototheniidae Trematomus bernacchii, a key sentinel species for monitoring Antarctic ecosystems. After laboratory exposure to beta-naphthoflavone (betaNF), basal levels and time-course induction of CYP1A, CYP1B and CYP3A were measured as enzymatic activities, immunoreactive protein content and mRNA expression in liver, gills, intestine and heart. Additional analyses in the liver included enzymatic activities of testosterone hydroxylase, (omega)- and (omega-1)-lauric acid hydroxylase and some phase II enzymes related to the AhR battery genes, DT-diaphorase, glutathione S-transferases and UDP-glucuronyl transferases. Responsiveness of hepatic CYP1A1 after exposure to betaNF demonstrated an higher sensitivity of MEROD than EROD activity and long lasting expression of mRNA still induced after 20 days from the treatment. Testosterone metabolism, oxidation of lauric acid and activities of phase II enzymes were not affected by betaNF indicating that their modulation is not mediated by Ah receptor. Induction of CYP1A was more limited in gills and absent in intestine and heart. The first nucleotide sequence for CYP1B1 in an Antarctic fish has been obtained, revealing a homology of 89% and 72% respectively to CYP1B1 of plaice and CYP1B2 of carp. Constitutive expression of CYP1B1 was restricted to gills where it was also induced by betaNF. Obtained results represent an additional contribution to the ecotoxicological characterization of T. bernacchii and further support the use of biomarkers for early detection of chemical pollution in Antarctica.
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PMID:Presence and inducibility by beta-naphthoflavone of CYP1A1, CYP1B1 and phase II enzymes in Trematomus bernacchii, an Antarctic fish. 1764 6