Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Humics and pesticides are present in aquatic environment and the toxicological consequences of their chemical interaction is well studied. However, data concerning the mechanism of the biochemical action of humic-pesticide combinations are scarce, especially in vertebrates. Thus we have chosen to study the in vivo effects of the plant polyphenolic tannic acid and the pyrethroid insecticide deltamethrin [Decis] alone or in combination on hepatic xenobiotic-metabolizing enzyme activities and the associated redox-parameters in carp, as the complex assessment of these systems are regarded to serve as a relevant biomarker of environmental pollution. Stress effects and tissue damage were followed by determination of the plasma glucose level, the activities of plasma transaminases, and by electron microscopy. Tannic acid alone exerted weak prooxidant effect due to its marked antioxidant enzyme inhibitory activity. Deltamethrin, applied in a very low dose, induced oxyradical production in fish via activation of cytochrome P450 isozymes. This effect was promoted by the antioxidant enzyme inhibitory action of tannic acid, when the two chemicals were combined; however, the ultrastructural damage of the hepatocytes was reduced by the common cytoprotective capacity of the phenolic. Numerous humics are known to alter the toxicity of pesticides and their influence depends on their type and concentration. Therefore, our work taken together with other comparative studies may contribute to the assessment of the impact of humics in nature, especially in case of environmental pollution.
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PMID:Influence of the polyphenolic tannic acid on the toxicity of the insecticide deltametihrin to fish. A comparative study examining both biochemical and cytopathological parameters. 1237 15

Basil or sweet basil (Ocimum basilicum) is cultivated throughout India and is known for its medicinal value. The effects of doses of 200 and 400 mg/kg body weight of hydroalcoholic extract (80% ethanol, 20% water) of the fresh leaves of Ocimum basilicum on xenobiotic metabolizing Phase I and Phase II enzymes, antioxidant enzymes, Glutathione content, Lactate dehydrogenase and lipid peroxidation in the liver of 8-9 weeks old Swiss albino mice were examined. Furthermore, the anticarcinogenic potential of basil leaf extract was studied, using the model of Benzo(a)pyrene-induced forestomach and 7,12 dimethyl benz(a)anthracene (DMBA)-initiated skin papillomagenesis. The hepatic glutathione S-transferase and DT-diaphorase specific activities were elevated above basal level by basil leaf treatment (from p < 0.005 to p < 0.001). Basil leaf extract was very effective in elevating antioxidant enzyme response by increasing significantly the hepatic glutathione reductase (GR) (p < 0.005), superoxide dismutase (SOD) (p < 0.05), and catalase activities (p < 0.005). Reduced glutathione (GSH), the major intracellular antioxidant, showed a significant elevation in the liver (p < 0.005) and also in all the extrahepatic organs (from p < 0.05 to p < 0.005). In the forestomach, kidney and lung, glutathione S-transferase and DT-diaphorase levels were augmented significantly, varying from p < 0.01 to p < 0.001. There were significant decreases in lipid peroxidation and lactate dehydrogenase activity. Chemopreventive response was evident from the reduced tumor burden (the average number of papillomas/mouse, p < 0.005 to p < 0.001), as well as from the reduced percentage of tumor bearing-animals. Basil leaf, as deduced from the results, augmented mainly the Phase II enzyme activity that is associated with detoxification of xenobiotics, while inhibiting the Phase I enzyme activity. There was an induction in antioxidant level that correlates with the significant reduction of lipid peroxidation and lactate dehydrogenase formation. Moreover, Basil leaf extract was highly effective in inhibiting carcinogen-induced tumor incidence in both the tumor models at peri-initiational level.
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PMID:Chemomodulatory efficacy of basil leaf (Ocimum basilicum) on drug metabolizing and antioxidant enzymes, and on carcinogen-induced skin and forestomach papillomagenesis. 1507 Jan 64

Cytochromes P450 (CYP) constitute a superfamily of hemeproteins that play a vital role in the metabolism of a wide variety of endogenous and xenobiotic compounds. Xenobiotic metabolism and the role of CYP are of particular interest in studies regarding the prevention of the damage caused by chemical pollutants. We investigated, in this study, the interaction of Triton X-100 and Tween 80 with CYP and antioxidant defenses in Curimbata, a Brazilian fish. Aiming to clarify the effects of non-ionic surfactants in the monooxigenase system of fish through in vitro study, the effects of Triton X-100 and Tween 80 were analyzed using monooxygenases and antioxidant system as experimental model. Total CYP and EROD were strongly inhibited by Triton X-100 and Tween 80 in a concentration-dependent way; the content of CYP was reduced until zero while EROD activity was completely inhibited in the presence of Triton X-100 and more than 40% inhibited in the presence of Tween 80. Each surfactant causes a different effect on each antioxidant enzyme. No effect was detected in SOD activity in the presence of even Triton X-100 or Tween 80. Triton X-100 increase catalase activity, while Tween 80 decreases this enzyme activity. The molecular structure of the surfactants causes the alteration of this system, since they are able to interact with the microsomal protein, especially with monooxigenase's components, altering their conformation and, consequently destroying their function. Our results suggest that surfactants can interact with components of the microsomal system leading to inhibition of CYP. Therefore, CYP activity, which has been used as a biomarker of xenobiotic exposure, should be used as a marker in association with other enzymes.
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PMID:Interaction of non-ionic surfactants with hepatic CYP in Prochilodus scrofa. 1546 53

The present study is an effort to identify a potent chemopreventive agent against various diseases (including cancer) in which oxidative stress and cell proliferation plays an important causative role. This study was designed to investigate the effect of gallic acid against ferric nitrilotriacetic acid (Fe-NTA)-induced carcinogen/ drug metabolizing phase I and phase II enzymes, antioxidative parameters, kidney markers, tumour promotion markers and lipid peroxidation (LPO) in kidney of male Wistar rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) caused significant depletion in the detoxification and antioxidant enzyme armoury with concomitant elevation in renal LPO, serum creatinine, blood urea nitrogen, hydrogen peroxide generation, ornithine decarboxylase activity and [3H]thymidine incorporation into renal DNA. However, pretreatment of animals with gallic acid (10 and 20 mg/kg body weight) resulted in a significant decrease in the levels of the parameters measured (P <0.001). Renal glutathione content (P <0.001), glutathione metabolizing enzyme (P <0.001) and antioxidant enzyme levels were also recovered to a significant level (P <0.001). The enhanced reduced glutathione level and enzyme activities involved in xenobiotic metabolism and maintaining antioxidant status of cells are suggestive of a chemopreventive efficacy of gallic acid against Fe-NTA-mediated oxidative stress, toxicity and cell proliferative response in Wistar rats.
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PMID:Effect of gallic acid on renal biochemical alterations in male Wistar rats induced by ferric nitriloacetic acid. 1701 5

Phase II detoxification enzymes are responsible for the detoxification and elimination of activated carcinogens, and thus act as important biomarkers for chemoprevention. In this study, we tested the chemopreventive activity of taxifolin, a flavanon compound purified from a mongolian medicinal plant, by measuring quinone reductase (QR) activity in HCT 116 cells. Taxifolin induced significant QR activity, but displayed relatively low cytotoxicity in cells (chemoprevention index=5.75). To identify the target genes regulated by taxifolin, DNA microarray was performed with a 3K human cancer chip containing 3096 human genes associated with carcinogenesis. Significant analysis of microarray (SAM) revealed 428 differentially expressed (DE) genes as statistically significant, with a false discovery rate (FDR) of 57.2% (delta=0.3366). Sixty-five genes, including a few detoxification enzymes (NQO1, GSTM1) and an antioxidant enzyme (TXNRD1), were up-regulated and 363 genes were down-regulated in the presence of 60 microM taxifolin. In view of the finding that selected genes of interest contained antioxidant response element (ARE), we hypothesize that taxifolin modulates chemopreventive genes through activation of the ARE. Transient transfection experiments using the ARE QR-CAT construct demonstrate that taxifolin significantly activates ARE, but not xenobiotic response element (XRE). In conclusion, taxifolin acts as a potential chemopreventive agent by regulating genes via an ARE-dependent mechanism.
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PMID:The chemopreventive effect of taxifolin is exerted through ARE-dependent gene regulation. 1754 Nov 56

In this study, di(2-ethylhexyl)phthalate (DEHP) toxicities to Caenorhabditis elegans were investigated using multiple toxic endpoints, such as mortality, growth, reproduction and stress-related gene expression, focusing on the identification of chemical-induced gene expression as a sensitive biomarker for DEHP monitoring. The possible use of C. elegans as a sentinel organism in the monitoring of soil ecosystem health was also tested by conducting the experiment on the exposure of nematode to field soil. Twenty-four-hour median lethal concentration (LC50) data suggest that DEHP has a relatively high potential of acute toxicity to C. elegans. Decreases in body length and egg number per worm observed after 24h of DEHP exposure may induce long-term alteration in the growth and reproduction of the nematode population. Based on the result from the C. elegans genome array and indicated in the literatures, stress proteins, metallothionein, vitellogenin, xenobiotic metabolism enzymes, apoptosis-related proteins, and antioxidant enzyme genes were selected as stress-related genes and their expression in C. elegans by DEHP exposure was analyzed semi-quantitatively. Expression of heat shock protein (hsp)-16.1 and hsp-16.2 genes was decreased by DEHP exposure. Expression of cytochrome P450 (cyp) 35a2 and glutathione-S-transferease (gst)-4, phase I and phase II of xenobiotic metabolism enzymes, was increased by DEHP exposure in a concentration-dependent manner. An increase in stress-related gene expressions occurred concomitantly with the deterioration on the physiological level, which suggests an increase in expression of those genes may not be considered as a homeostatic response but as a toxicity that might have physiological consequences. The experiment with the soil from the landfill site suggests that the potential of the C. elegans biomarker identified in laboratory conditions should be calibrated and validated for its use in situ.
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PMID:Toxic effects of di(2-ethylhexyl)phthalate on mortality, growth, reproduction and stress-related gene expression in the soil nematode Caenorhabditis elegans. 1760 95

Intake of ergot alkaloids found in endophyte-infected tall fescue grass is associated with decreased feed intake and reduction in body weight gain. The liver is one of the target organs of fescue toxicosis with upregulation of genes involved in xenobiotic metabolism and downregulation of genes associated with antioxidant pathways. It was hypothesized that short-term exposure of rats to ergot alkaloids would change hepatic cytochrome P450 (CYP) and antioxidant expression, as well as reduce antioxidant enzyme activity and hepatocellular proliferation rates. Hepatic gene expression of various CYPs, selected nuclear receptors associated with the CYP induction, and antioxidant enzymes were measured using real-time PCR. Hepatic expression of CYP, antioxidant and proliferating cell nuclear antigen (PCNA) proteins were measured using Western blots. The CYP3A1 protein expression was evaluated using primary rat hepatocellular cultures treated with ergovaline, one of the major ergot alkaloids produced by fescue endophyte, in order to assess the direct role of ergot alkaloids in CYP induction. The enzyme activities of selected antioxidants were assayed spectrophotometrically. While hepatic CYP and nuclear receptor expression were increased in ergot alkaloid-exposed rats, the expression and activity of antioxidant enzymes were reduced. This could potentially lead to increased oxidative stress, which might be responsible for the decrease in hepatocellular proliferation after ergot alkaloid exposure. This study demonstrated that even short-term exposure to ergot alkaloids can potentially induce hepatic oxidative stress which can contribute to the pathogenesis of fescue toxicosis.
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PMID:Effect of ergot alkaloids associated with fescue toxicosis on hepatic cytochrome P450 and antioxidant proteins. 1820 39

Heme oxygenase (HO)-1 is a protective antioxidant enzyme that prevents cardiomyocyte apoptosis, for instance, during progressive cardiomyopathy. Here we identify a fundamental aspect of the HO-1 protection mechanism by demonstrating that HO-1 activity in mouse heart stimulates the bigenomic mitochondrial biogenesis program via induction of NF-E2-related factor (Nrf)2 gene expression and nuclear translocation. Nrf2 upregulates the mRNA, protein, and activity for HO-1 as well as mRNA and protein for nuclear respiratory factor (NRF)-1. Mechanistically, in cardiomyocytes, endogenous carbon monoxide (CO) generated by HO-1 overexpression stimulates superoxide dismutase-2 upregulation and mitochondrial H(2)O(2) production, which activates Akt/PKB. Akt deactivates glycogen synthase kinase-3beta, which permits Nrf2 nuclear translocation and occupancy of 4 antioxidant response elements (AREs) in the NRF-1 promoter. The ensuing accumulation of nuclear NRF-1 protein leads to gene activation for mitochondrial biogenesis, which opposes apoptosis and necrosis caused by the cardio-toxic anthracycline chemotherapeutic agent, doxorubicin. In cardiac cells, Akt silencing exacerbates doxorubicin-induced apoptosis, and in vivo CO rescues wild-type but not Akt1(-/-) mice from doxorubicin cardiomyopathy. These findings consign HO-1/CO signaling through Nrf2 and Akt to the myocardial transcriptional program for mitochondrial biogenesis, provide a rationale for targeted mitochondrial CO therapy, and connect cardiac mitochondrial volume expansion with the inducible network of xenobiotic and antioxidant cellular defenses.
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PMID:Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1. 1902 15

Filterfeeders, such as bivalves, are highly affected during toxic cyanobacterial blooms, as they are non-selective and may use the cyanobacteria as main nutrition source. The freshwater mussel Dreissena polymorpha, living in lakes and rivers coexisting with cyanobacteria, was exposed to 100 microg L(-1) microcystin-LR (MC-LR) for up to three days. MC-LR concentration in mussel tissue and surrounding media was quantified by HPLC-PDA during uptake and depuration phase, revealing an immediate, continuous uptake, and release of non-metabolized toxin, and occurrence of reincorporation. The involvement of multi-xenobiotic-resistance protein (P-glycoprotein, P-gp) on the excretion of MC-LR was evidenced by efflux and accumulation version of the Rhodamine Assay as well as on P-gp gene expression. P-gp expression was enhanced after 1 h exposure but no changes were detected after longer (72 h) exposure. P-gp enzyme activity showed a significant increase with exposure time, supporting the hypothesis that P-gp is involved in the excretion of MC-LR. Induction of biotransformation enzyme such as pi-class glutathione S-transferase (piGST) and antioxidant enzyme catalase (CAT) was immediately inhibited and returned to control values only after more than 72 h expose time. Heat shock protein 70 (hsp70) and protein phosphatase 2A (PP2A) gene expression was not changed due to the treatment with cyanobacterial toxin MC-LR.
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PMID:Multi-xenobiotic-resistance a possible explanation for the insensitivity of bivalves towards cyanobacterial toxins. 1893 Jul 53

Exposure to ergot alkaloids in endophyte-infected fescue (E+) is associated with impaired animal productivity, especially during heat stress, which is commonly referred to as fescue toxicosis. To elucidate the pathogenesis of this condition, the effects of short-term heat stress (HS) on hepatic gene expression in rats exposed to endophytic ergot alkaloids were evaluated. Rats implanted with telemetric transmitters to continuously measure core temperature were fed an E+ diet and maintained under thermoneutral (TN) conditions (21 degrees C) for 5 d, followed by TN or 31 degrees C (HS) conditions for 3 d. Feed intake (FI) and BW were monitored daily. The E+ and HS-induced alterations in hepatic genes were evaluated using DNA microarrays and PCR analyses. Hepatic antioxidant enzyme activities, as well as the incidence of apoptosis, were determined. As expected, intake of E+ reduced FI and BW from pretreatment levels under TN conditions, with greater reductions during short-term HS. Genes involved in gluconeogenesis and apoptosis were upregulated, whereas genes associated with oxidative phosphorylation, xenobiotic metabolism, antioxidative mechanisms, immune function, cellular proliferation, and chaperone activity were all downregulated with short-term HS. Hepatocytic apoptosis was increased and antioxidant enzyme activity decreased in the livers of rats exposed to HS. The hypothesized, exacerbating effects of HS on the direct, endophytic toxin-related and indirect, reduced caloric intake-associated alterations in hepatic gene expression were clearly demonstrated in rats and may help to elucidate the pathogenesis of fescue toxicosis in various animal species.
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PMID:Effects of short-term heat stress on endophytic ergot alkaloid-induced alterations in rat hepatic gene expression. 1957 62


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