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)

Metanil yellow, a non-permitted colour for food commodities, is used in the leather, paper and textile industries. In this paper the effect of oral and parenteral administration of Metanil yellow on hepatic and intestinal biochemical parameters was investigated. Oral administration of Metanil yellow (430 mg kg-1 body wt.) for 7 days caused significant depletion of hepatic and intestinal glutathione levels (33-52%) with a concomitant increase in lipid peroxidation (49-121%). Metanil yellow treatment for 7 days also led to a significant increase in cytochrome P-450 (P-450)-dependent aryl hydrocarbon hydroxylase (AHH) activity (99-223%) in the liver and intestine. Cytosolic glutathione-S-transferase (GST) (32-136%) and quinone reductase (QR) (20-92%) activities were also found to be substantially induced in hepatic and intestinal tissues following oral treatment of Metanil yellow. It is interesting to note that oral treatment of Metanil yellow showed a greater response in cytosolic enzymes of hepatic tissue as compared to intestine. Single parenteral administration of Metanil yellow (80 mg kg-1 body wt.) caused significant induction of P-450 and its dependent monooxygenases. Even after 5 days of single parenteral administration of Metanil yellow, hepatic AHH activity showed an elevation of 48% while other monooxygenases were marginally increased. Cytosolic GST and QR showed respective peak inductions of 92% and 60% after 2 and 3 days of parenteral administration of Metanil yellow, which levels off after the 5th day. It can be concluded that Metanil yellow acts as an inducer of a specific form of microsomal P-450 and cytosolic GST and QR, which may involve a cytosolic Ah receptor.
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PMID:Effect of oral and parenteral administration of metanil yellow on some hepatic and intestinal biochemical parameters. 904 33

Metanil yellow, a non-permitted food colour, has been found in various foodstuffs. The induction potential of metanil yellow on hepatic microsomal cytochrome P-450 (P-450)-dependent monooxygenases and cytosolic detoxification enzymes, namely, glutathione S-transferase (GST) and quinone reductase (QR), was investigated. Oral administration of metanil yellow (430 mg/kg body weight) to four animals for seven days caused significant induction of hepatic P-450 (48%) and its dependent aryl hydrocarbon hydroxylase (100%) activity and cytosolic GST (136%) and QR (92%) activities. Parenteral administration of metanil yellow (80 mg/kg body weight) to another set of four animals for 3 days resulted in higher induction of ethoxyresorufin-O-deethylase (228%) as compared to other monooxygenases (64-92%), while GST and QR were also found to be induced (59-95%). Spectra of metanil yellow-induced microsomes showed an increase in P-450 with a shift of 2.2 nm in the soret region. The results suggest that metanil yellow acts as a bifunctional inducer of specific isozymes of P-450 and cytosolic enzymes and thus may involve the cytosolic aryl hydrocarbon (Ah) receptor for this type of induction.
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PMID:Metanil yellow: a bifunctional inducer of hepatic phase I and phase II xenobiotic-metabolizing enzymes. 935 Feb 29

Our recent studies have shown that vanadium, a dietary micronutrient, has an inhibitory response against experimentally induced rat liver carcinogenesis. In the present study, the effect of vanadium on hepatic xenobiotic biotransformation in rats exposed to diethylnitrosamine (DENA, 200 mg/kg, IP) was investigated to elucidate a possible mechanism of vanadium-mediated prevention of chemical carcinogenesis. Supplementary vanadium in drinking water at 0.5 parts per million (ppm) was employed ad lib before and after the intiation with DENA, before the initiation only, or during the promotional event. After 20 weeks, there was a significant reduction of hepatocyte nodules (HNs) (P<0.01), nodule multiplicity (P<0.001), and the number of nodules more than 3 mm in size in the long-term vanadium-supplemented rats than their DENA control counterparts. Total cytochrome P450 and b5 contents as well as cytochrome P450 2E1 (CYP2E1, EC 1.5.99), aryl hydrocarbon hydroxylase (AHH, EC 1.14.14.2), and UDP-glucuronyl transferase (UDPGT, EC 2.4.1.17) activities in the microsomal fractions of HNs and nonnodular surrounding parenchyma (NNSP) were found to be significantly decreased in DENA control group compared to untreated normal control. Though supplementary vanadium had little or no influence on the contents of cytochrome P450 and b5 and activities of CYP2E1 and AHH in HNs and NNSP, it substantially elevated the UDPGT activity in both HNs and NNSP liver areas. DENA treatment alone also brought about a sharp decrease in cytosolic UDP-glucose dehydrogenase (EC 1.1.1.22), DT-diaphorase (EC 1.6.99.2), and glutathione S-transferase (EC 2.5.1.18) activities in HNs and NNSP compared to normal liver. Supplementary vanadium was found to exert a marked induction in these cytosolic enzymes in HNs as well as NNSP when compared to DENA control. A positive correlation of phase I and phase II drug metabolizing enzymes in HNs or NNSP was always observed in DENA or DENA plus long-term vanadium-treated group. It is concluded that the chemoprotective effect of vanadium may be attributed to the substantial elevation of phase II conjugating enzymes, which may lead to a move and shift of the metabolic profile that may reduce the intracellular concentration of carcinogen-derived reactive intermediates.
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PMID:Characterization of selective induction and alteration of xenobiotic biotransforming enzymes by vanadium during diethylnitrosamine-induced chemical rat liver carcinogenesis. 1045 Oct 30

Benzanthrone (BA) and 3-bromobenzanthrone (3-BBA) are important dye intermediates used in the manufacture of various vat and disperse dyes. BA has been implicated as a cause of hepatic malfunctions and dermal lesions in workers. However, not much information on halogenated BAs, especially 3-BBA, is available. Experiments were designed to undertake a comparative safety assessment of both BA and 3-BBA, given orally at a dose of 50 mg/kg body weight for 10 days to guinea pigs. There was a significant decrease (25%) in body weight with 3-BBA, whereas BA treatment did not cause any change. Serum glutamate oxaloacetate transaminase and glutamate pyruvate transminase were found to be significantly (P<0.05) increased in 3-BBA- as well as in BA-treated animals. 3-BBA and BA led to substantial depletion of ascorbic acid in both liver and adrenal glands. However, depletion of ascorbic acid was more pronounced with 3-BBA (19.2-28.3%) than with BA (13.5-16.6%). 3-BBA and BA treatments caused 80% and 24% depletion of hepatic free sulfydryl content, while lipid peroxidation showed a significant enhancement of 73% and 47%, respectively. BA and 3-BBA caused decreases in cytochrome P-450 content and phase I enzymes particularly ethoxyresorufin- O-deethylase and aryl hydrocarbon hydroxylase, whereas phase II enzymes (quinone reductase and glutathione- S-transferase) were substantially increased. Activities of bio-antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase, were significantly increased by 153, 104, 20 and 67% in the 3-BBA-treated group, whereas the degree of increase in these parameters was relatively less in BA-treated group. The data indicate that both BA and 3-BBA can disturb membrane integrity by decreasing endogenous glutathione and ascorbic acid levels with a concomitant increase in lipid peroxidative damage. This may in turn lead to impairment of hepatic P-450-dependent monooxygenase, while the changes in antioxidant enzymes reveal oxidative stress. 3-BBA treatment caused dilation of portal triad with thickening of arterial wall, hyperplasia of Kupffer cells and influx of inflammatory cells between hepatic cords, which could be due to formation of Br(*) radical or due to formation of semiquinone type of intermediate following oxidation. The results may be interpreted to mean that industrial workers exposed to 3-BBA are at higher risk than those exposed to BA, and necessary precautions should be taken to safeguard their exposure risks.
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PMID:Comparative effect of benzanthrone and 3-bromobenzanthrone on hepatic xenobiotic metabolism and anti-oxidative defense system in guinea pigs. 1259 Mar 61

Several naturally occurring plant phenols were shown to inhibit the mutagenicity and/or tumorigenicity of chemical carcinogens, including polycyclic aromatic hydrocarbons (PAHs). In this study, the effect of the topical application of three structurally diverse phenolic acids and trihydroxystilbene, resveratrol, on epidermal aryl hydrocarbon hydroxylase (AHH), phase II enzymes, as well as the binding of benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA) to epidermal DNA were compared. The single, topical application of 8 and 16 mumol of protocatechuic or chlorogenic acid increased the activity of AHH by 10-30%, whereas resveratrol in a dose of 16 mumol almost completely (99%) inhibited the enzyme activity. Phenolic acids also increased the activities of phase II enzymes. Resveratrol did not affect the glutathione S-transferase activity but induced UDP glucuronosyltransferase (by approximately 100-150%) and to a lesser extent NAD(P)H:quinone oxidoreductase. In a dose of 16 micromol all phenolic acids afforded 40-50% inhibition of covalent benzo[a]pyrene-diol-epoxide (B[a]PDE) binding to DNA. Resveratrol had no effect on B[a]PDE adduct formation but reduced the levels of all the major DMBA adducts. Phenolic acids, particularly tannic acid, mostly affected the formation of syn- and anti-DMBADE dAdo adducts. These results indicate that both the modulation of carcinogen activating enzymes and the prevention of their ultimate metabolites binding to DNA by naturally occurring phenolics are involved in the antitumorigenic activity of these compounds. For phenolic acids, however, their interactions with reactive PAH metabolites and/or blocking of a specific binding site in a genome seem more important. Derivatives of stilbene, such as resveratrol, affect DNA adduct formation and thus the initiation of tumorigenesis through the interaction with the Ah receptor rather than the scavenging active metabolites.
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PMID:Alteration in phase I and II enzyme activities and polycyclic aromatic hydrocarbons-DNA adduct formation by plant phenolics in mouse epidermis. 1520 80

Apigenin, a bioflavonoid, is abundantly present in fruits and vegetables and possesses potential chemopreventive properties against a wide variety of chronic diseases. In this study we investigated the anti-genotoxic effects of apigenin against a known genotoxicant, benzo(a)pyrene (B(a)P) (125 mg kg(-1) orally) toxicity in Swiss albino mice. B(a)P administration led to induction of cytochrome P-450 (CYP), aryl hydrocarbon hydroxylase (AHH) and DNA strand breaks (P < 0.001), which was suppressed by apigenin (2.5 and 5 mg kg(-1) orally) dose dependently (P < 0.001). B(a)P-induced depletion in the level of reduced glutathione (GSH), quinone reductase (QR) and glutathione-S-transferase (GST) was also shown to be restored by apigenin pre-treatment (P < 0.001). A simultaneous significant and dose-dependent reduction was noted in DNA strand breaks and in-vivo DNA damage (P < 0.001), which gives some insight into restoration of DNA integrity in modulator groups. These results strongly support the protective nature of apigenin against B(a)P-induced toxicity.
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PMID:Inhibitory effect of apigenin on benzo(a)pyrene-mediated genotoxicity in Swiss albino mice. 1733 30

Environmental factors have been speculated to play an important role in potentiating the neurotoxicity of Lathyrus sativus (LS). Hence, blood-brain barrier permeability and neurotoxicity studies were carried out in manganese- and LS-exposed animals. Dietary feeding of LS (80%) plus Mn (0.4 mg/100 g diet) for 90 days to guinea pigs showed significant (p < 0.05) decrease in brain nucleotidase and ATPase activities when compared to control or LS alone treated groups. Combined treatment of LS and Mn showed a significant (p < 0.05) decrease in neuronal aryl hydrocarbon hydroxylase (36-40%), ethoxyresorufin-O-deethylase (40-45%), glutathione-S-transferase (27-31%), and quinone reductase (24-25%) activities when compared to control and LS alone treated animals. Lipid peroxidation, a marker for membrane damage, was found to be relatively more enhanced (58-141%) along with significant (p < 0.05) depletion of GSH levels in LS+Mn-treated animals when compared to control, Mn alone, and LS alone treated groups. The neuronal catalase activity of lathyrus plus Mn-treated animals showed a pronounced decrease (37-49%) when compared to control, Mn, and lathyrus alone treated groups. On the contrary, glutathione peroxidase in brain of Mn and lathyrus alone treated animals indicated a respective increase (p < 0.05) of 18% and 20%, while the combined effect of lathyrus plus Mn exhibited an increase of almost 50% when compared to control guinea pigs. Single parenteral administration of Mn (15 mg/kg b.wt) to guinea pigs followed by single oral intubation of beta-N-oxalyl-L-alpha, beta-diamino propionic acid (ODAP, 75 mg/guinea pig) resulted in a significant increase (143%) in neuronal ODAP content. ODAP (50 mg/kg,iv) treatment to mice pretreated with MnCl2 (10 mg/kg b.wt for 3 days or 40 mg/kg b.wt for 1 day), caused an enhancement in blood-brain barrier (BBB) permeability (129-196%), while ODAP and Mn alone showed relatively less enhancement (66-87%). The lumbar region of LS+Mn showed a number of vacuolated areas of variegated size and chromatolytic neurons, along with a few degenerated neurons. These results suggest that Mn may potentiate the neurotoxicity of lathyrus/ODAP by altering the BBB permeability.
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PMID:Potentiation of neurotoxicity of Lathyrus sativus by manganese: alterations in blood-brain barrier permeability. 1977 23

The modulation in biochemical status of skin and hepatic tissue at the time point of commencement of promotion stage of skin carcinogenesis in mice and its intervention with aqueous Azadirachta indica leaf extract (AAILE) were investigated. 7,12-Dimethylbenz(a)anthracene (DMBA, 500 nmol/100 ul of acetone) was applied topically for 2 weeks (twice weekly), followed by phorbol-12-myristate-13-acetate (TPA, 1.7 nmol/100 ul) twice weekly for 6 weeks on the depilated skin of mice and AAILE was administered orally at a dose level of 300 mg/kg body wt thrice a week for 10 weeks. DMBA/TPA treatment upregulated the phase I enzymes in skin and hepatic tissue, as revealed by the increased cytochrome P450 (CYP) and cytochrome b5 (cyt b5) levels and aryl hydrocarbon hydroxylase (AHH) activity when compared to the control group and differentially modulated the activities of phase II enzymes like glutathione-s-transferase (GST), DT-diaphorase (DTD) and uridine diphosphate glucuronosyltransferase (UDP-GT). AAILE treatment decreased the DMBA/TPA-induced increase in cutaneous CYP level and enhanced the DTD and UDP-GT activities when compared with DMBA/TPA group. In the hepatic tissue of AAILE + DMBA/TPA group, an increase in UDP-GT activity was observed when compared to DMBA/TPA group. DMBA/TPA treatment did not alter the skin lipid peroxidation (LPO) level when compared to control group, however, in the animals that received AAILE treatment along with DMBA/TPA, a significant increase in LPO was observed when compared to control group. This was associated with a decrease, in cutaneous reduced glutathione (GSH) level of AAILE + DMBA/TPA group. Enhanced LPO level was observed in the hepatic tissue of DMBA/TPA and AAILE + DMBA/TPA groups when compared to control group. However, no alteration was observed in their hepatic GSH levels. The micronuclei score in hepatic tissue did not exhibit significant inter-group differences. The results of the present study suggest that apart from skin, liver may be affected during DMBA/TPA-induced skin tumorigenesis. AAILE treatment has the ability to modulate these changes potentially influencing the process of tumor formation. These findings seem to be important to carcinogenesis and its intervention with anti-cancer agents.
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PMID:Modulatory effects of Azadirachta indica leaf extract on cutaneous and hepatic biochemical status during promotion phase of DMBA/TPA-induced skin tumorigenesis in mice. 2372 Aug 84


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