• Title/Summary/Keyword: detoxifying enzymes

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Investigation of the efficacy of mycotoxin-detoxifying additive on health and growth of newly-weaned pigs under deoxynivalenol challenges

  • Holanda, Debora Muratori;Kim, Sung Woo
    • Animal Bioscience
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    • v.34 no.3_spc
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    • pp.405-416
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    • 2021
  • Objective: This study evaluated the effects of feeding diets naturally contaminated with deoxynivalenol (supplemental 2 mg/kg) on health, growth, and the effects of a mycotoxin-detoxifying additive in newly-weaned pigs. Methods: Thirty-six pigs (27 day-old) were housed individually and assigned to 3 treatments for 5 weeks: CON (diet containing minimal deoxynivalenol), MT (diet with supplemental 1.9 mg/kg of deoxynivalenol), and MT+D (MT + mycotoxin-detoxifying additive, 0.2%, MegaFix, ICC, São Paulo, Brazil). The mycotoxin-detoxifying additive included bentonite, algae, enzymes, and yeast. Blood was taken at week 2 and 5. Jejunal tissue were taken at week 5. Data were analyzed using the MIXED procedure of SAS. Results: Pigs fed MT+D tended to have decreased (p = 0.056) averaged daily feed intake during week 1 than MT. At week 2, serum aspartate aminotransferase/alanine aminotransferase in MT tended to be lower (p = 0.059) than CON, whereas it was increased (p<0.05) for MT+D than MT, indicating hepatic damages in MT and recovery in MT+D. Pigs fed MT had lower (p<0.05) blood urea nitrogen/creatinine than CON, supporting hepatic damage. At week 5, pigs fed MT tended to have reduced (p = 0.079) glucose than CON, whereas it was increased (p<0.05) for MT+D than MT, indicating impaired intestinal glucose absorption in MT, which was improved in MT+D. Pigs fed CON tended to have increased (p = 0.057) total glutathione in jejunum than MT, indicating oxidative stress in MT. Pigs fed MT+D had a reduced (p<0.05) proportion of Ki-67-positive cells in jejunum than MT, indicating lower enterocyte proliferation in MT+D. Conclusion: Feeding supplemental 1.9 mg/kg of deoxynivalenol reduced growth and debilitated hepatic health of pigs, as seen in leakage of hepatic enzymes, impaired nitrogen metabolism, and increase in oxidative stress. The mycotoxin-detoxifying enhanced hepatic health and glucose levels, and attenuated gut damage in pigs fed deoxynivalenol contaminated diets.

Potential Chemoprevention Activity of Pterostilbene by Enhancing the Detoxifying Enzymes in the HT-29 Cell Line

  • Harun, Zaliha;Ghazali, Ahmad Rohi
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6403-6407
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    • 2012
  • Detoxifying enzymes are present in most epithelial cells of the human gastrointestinal tract where they protect against xenobiotics which may cause cancer. Induction of examples such as glutathione S-transferase (GST) and its thiol conjugate, glutathione (GSH) as well as NAD(P)H: quinoneoxidoreductase (NQO1) facilitate the excretion of carcinogens and thus preventing colon carcinogenesis. Pterostilbene, an analogue of resveratrol, has demonstrated numerous pharmacological activities linked with chemoprevention. This study was conducted to investigate the potential of pterostilbene as a chemopreventive agent using the HT-29 colon cancer cell line to study the modulation of GST and NQO1 activities as well as the GSH level. Initially, our group, established the optimum dose of 24 hours pterostilbene treatment using MTT assays. Then, effects of pterostilbene ($0-50{\mu}M$) on GST and NQO1 activity and GSH levels were determined using GST, NQO1 and Ellman assays, respectively. MTT assay of pterostilbene ($0-100{\mu}M$) showed no cytotoxicity toward the HT-29 cell line. Treatment increased GST activity in the cell line significantly (p<0.05) at 12.5 and $25.0{\mu}M$. In addition, treatment at $50{\mu}M$ increased the GSH level significantly (p<0.05). Pterostilbene also enhanced NQO1 activity significantly (p<0.05) at $12.5{\mu}M$ and $50{\mu}M$. Hence, pterostilbene is a potential chemopreventive agent capable of modulation of detoxifiying enzyme levels in HT-29 cells.

Protection by Chrysanthemum zawadskii extract from liver damage of mice caused by carbon tetrachloride is maybe mediated by modulation of QR activity

  • Seo, Ji-Yeon;Lim, Soon-Sung;Park, Ji-A;Lim, Ji-Sun;Kim, Hyo-Jung;Kang, Hui-Jung;YoonPark, Jung-Han;Kim, Jong-Sang
    • Nutrition Research and Practice
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    • v.4 no.2
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    • pp.93-98
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    • 2010
  • Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by $CCl_4$ treatment to the control level. Hepatic injury induced by $CCl_4$ was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by $CCl_4$.

The Protective Effects of Curcuma longa Linn. Extract on Carbon Tetrachloride-Induced Hepatotoxicity in Rats via Upregulation of Nrf2

  • Lee, Hyeong-Seon;Li, Li;Kim, Hyun-Kyung;Bilehal, Dinesh;Li, Wei;Lee, Dong-Seok;Kim, Yong-Ho
    • Journal of Microbiology and Biotechnology
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    • v.20 no.9
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    • pp.1331-1338
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    • 2010
  • This study was designed to investigate the potentially protective effects of Curcuma longa Linn. extract (CLE) on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in rats. Male Sprague-Dawley rats were pretreated with 50 or 100mg/kg of CLE or 100mg/kg of butylated hydroxytoluene(BHT) for 14 days before $CCl_4$ administration. In addition, the CLE control group was pretreated with 100mg/kg CLE for only 14 days. Three hours after the final treatment, a single dose of $CCl_4$ (20mg/kg) was administrated intraperitoneally to each group. After the completion of this phase of the experiment, food and water were removed 12 h prior to the next step. The rats were then anesthetized by urethane and their blood and liver were collected. It was observed that the aspartate aminotransferase and alanine aminotransferase activities of the serum, and the hepatic malondialdehyde levels had significantly decreased in the CLE group when compared with the $CCl_4$-treated group. The antioxidant activities, such as superoxide dismutase, catalase, and glutathione peroxidase activities, in addition to glutathione content, had increased considerably in the CLE group compared with the $CCl_4$-treated group. Phase II detoxifying enzymes, such as glutathione S-transferase, were found to have significantly increased in the CLE group as opposed to the $CCl_4$-treated group. The content of Nrf2 was determined by Western blot analysis. Pretreated CLE increased the level of nuclear translocated Nrf2, and the Nrf2 then increased the activity of the antioxidant and phase II detoxifying enzymes. These results indicate that CLE has protective effects against $CCl_4$-induced hepatotoxicity in rats, via activities of antioxidant and phase II detoxifying enzymes, and through the activation of nuclear translocated Nrf2.

Schisandra Chinensis Baillon regulates the gene expression of phase II antioxidant/detoxifying enzymes in hepatic damage induced rats

  • Jang, Han I;Do, Gyeong-Min;Lee, Hye Min;Ok, Hyang Mok;Shin, Jae-Ho;Kwon, Oran
    • Nutrition Research and Practice
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    • v.8 no.3
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    • pp.272-277
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    • 2014
  • BACKGROUND/OBJECTIVES: This study investigated the antioxidant activities and hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats. MATERIALS/METHODS: Sprague-Dawley (SD) rats were pretreated with SCE (300, 600, and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each animal, except those belonging to the normal control group, were injected with t-BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP injection. RESULTS: Although no significant differences in AST and ALT levels were observed among the TC and SCE groups, the high-dose SCE group showed a decreasing tendency compared to the TC group. However, erythrocyte SOD activity showed a significant increase in the low-dose SCE group compared with the TC group. On the other hand, no significant differences in hepatic total glutathione (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) activities were observed among the TC and SCE groups. Hepatic histopathological evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced incidence of lesions, such as neutrophil infiltration, swelling of liver cells, and necrosis. In particular, treatment with a high dose of SCE resulted in induction of phase II antioxidant/detoxifying enzyme expression, such as glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit (GCLC). CONCLUSIONS: Based on these results, we conclude that SCE exerts protective effects against t-BHP induced oxidative hepatic damage through the reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In addition, SCE regulates the gene expression of phase II antioxidant/detoxifying enzymes independent of hepatic antioxidant enzyme activity.

Cytoprotection Against Oxidative Damage by Nrf2-regulated Genes

  • Kwak, Mi-Kyoung;Kensler, Thomas W.
    • Toxicological Research
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    • v.23 no.3
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    • pp.207-214
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    • 2007
  • Chronic oxidative stress produced by exposure to environmental chemicals or pathophysiological states can lead animals to aging, carcinogenesis and degenerative diseases. Indirect antioxidative mechanisms, in which natural or synthetic agents are used to coordinately induce the expression of cellular antioxidant capacity, have been shown to protect cells and organisms from oxidative damages. Electrophile and free radical detoxifying enzymes, which were originally identified as the products of genes induced by cancer chemopreventive agents, are members of this protective system. The NFE2 family transcription factor Nrf2 was found to govern expression of these detoxifying enzymes, and screening for Nrf2-regulated genes has identified many gene categories involved in maintaining cellular redox potential and protection from oxidative damage as Nrf2 downstream genes. Further, studies using Nrf2-deficient mice revealed that these mutant mice showed more susceptible phenotypes towards exposure to environmental chemicals/carcinogens and in oxidative stress related disease models. With the finding that cancer chemopreventive efficacy of indirect antioxidants (enzyme inducers) is lost in the absence of Nrf2, a central role of Nrf2 in the antioxidative protective system has been firmly established. Promising results from cancer prevention clinical trials using enzyme inducers propose that pharmacological interventions that modulate Nrf2 can be an effective strategy to protect tissues from oxidative damage.

Reciprocal Effect of DHEA and Rietary Fat on Glutathione Utilizing Detoxifying System in Rat Liver Tissue

  • Kwak, Chung-Shil;Kwon, In-Soon;Park, Sang-Chul
    • Nutritional Sciences
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    • v.3 no.1
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    • pp.11-17
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    • 2000
  • This study was intended to examine whether dehydroepiandrosterone (DHEA) and dietary fat level or source could modulate glutathione utilizing detoxifying system activity and the cytosolic NADPH generation in rat liver. Male Sprague-Dawley rats were fed semipurifed diet containing either 2%(w/w) corn oil (low level of corn oil diet: 5 ca% of fat) 15% corn oil (high level of corn oil diet: 31 cal% of fat) or 13% sardine oil plus 2% corn oil(high level of fish oil diet: 31 cal% of fat) for 9 weeks. Half of the rats in each diet group were fed a diet supplemented with 0.2% DHEA (w/w). DHEA administration increased plasma total cholesterol level in low corn oil diet-fed rats. The high fish oil diet significantly decreased plasma total cholesterol level compared to the high corn oil diet. Plasma triglyceride level was not significantly changed by DHEA administration and dietary fat level and source. Fasting plasma glucose level was increased by DHEA administration and fish oil diet. Glucose 6-phosphate dehydrogenase activity in liver tissue was significantly increased by DHEA administration and high fat diet, especially fish oil diet. Malic enzyme activity in liver tissue was significantly increased by DHEA administration and high fat diet, especially fish oil diet. Malic enzyme activity in liver tissue was significantly increased by DHEA administration. DHEA suppressed the glutathione peroxidase, glutathione-dependent enzymes compared to the low corn oil diet, while fish oil diet elevated the activity of glutathione peroxidase and glutathione reductase compared to corn oil diet. These results suggest that DHEA administration and high level of corn oil diet may suppress the cellular detoxifying system activity through reduction of glutathione utilization, while the fish oil diet did not show these effects.

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Cadmium-Induced Phytotoxicity in Tomato Seedlings Due to the Accumulation of H2O2 That Results from the Reduced Activities of H2O2 Detoxifying Enzymes

  • Cho, Un-Haing
    • The Korean Journal of Ecology
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    • v.27 no.2
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    • pp.107-114
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    • 2004
  • Tomato (Lycopersicon esculentum) seedlings exposed to various concentrations of $CdC1_2$ (0∼100 $\mu$M) in the nutrient solution for up to 9 days were analyzed with the seedling growth, $H_2O_2$ production, glutathione levels and activity changes of enzymes related to $H_2O_2$ removal. The growth of seedlings was inhibited with over 50 $\mu$M Cd, whereas the levels of $H_2O_2$ and glutathione were enhanced with Cd exposure level and time. Meanwhile, Cd exposure increased the activities of catalase (CAT) and glutathione reductase (GR) but decreased the activities of dehydroascorbate acid reductase (DHAR) and ascorbate peroxidase (APX) in both leaves and roots. These results suggest that the altered activities of antioxidant enzymes particularly involved in the $H_2O_2$ removal and the subsequent $H_2O$$_2$ accumulation could induce the Cd-induced phytotoxicity.

Inhibition of Vinyl Carbamate Epoxide- and 2`-(4-Nitrophenoxy)oxirane-induced Mutagenicity by Various Nucleophilic Compounds and Detoxifying Enzymes (Vinyl Carbamate Epoxide와 2`-(4-Nitrophenoxy)oxirane으로 유발된 돌연변이에 대한 친핵성 물질 및 해독작용 효소에 의한 억제)

  • 박광균;이자현;김혜원;김종우;김윤수
    • Environmental Mutagens and Carcinogens
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    • v.17 no.2
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    • pp.97-108
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    • 1997
  • The drugs or xenobiotics introduced to the body, are detoxified through the process of biotransformation in the body. In this process, most of the insoluble compounds become more polar, soluble and easily excretable. But, parts of introduced materials are metabolized to highly reactive electrophilic carcinogens through activation pathways. These metabolites are toxic and can react with DNA, RNA and proteins which are nucleophilic compounds. The objective of this study is to illustrate the aleactivation pathways of two highly reactive epoxide compounds, vinyl carbamate epoxide (VCO) and 2'-(4-nitrophenoxy)oxirane (NPO). They are the ultimate electrophilic carcinogens of ethyl carbamate(urethane) and 4-nitrophenyl vinyl ether, respectively. In this research, we studied the inhibition of the mutagenic activities of VCO or NPO by nuchieophiles [glutahione(GSH) and N-acetylcysteine(NAC)], detoxifying enzymes[epoxide hydrolase and glutathione-S-transferase(GST)] and intracellular organelles (microsomes and cytosol). In addition we also tested the suppression of DNA adducts formation by GSH and NAC. The results are summerized as follow. 1. The microsomes and cytosol which contain epoxide hydrolase and GST, respectively, decreased the mutagenicity of VCO (74% and 95%, respecfivel), and NPO (35% and 93%, respectively). The nucleophilic GSH and NAC decreased the mutagenicity by 86% (VCO) and 80% (NPO), 76% (VCO) and 40% (NPO), respectively. 2. The purified epoxide hydrolase decreased the mutagenicity of two epoxides in a dose-dependent manner, and GSH also decreased the mutagenicity in the presence of GST. 3. Formation of two DNA adducts, 7-(2'-oxoethyi)guanine (OEG) and N2,3-ethenoguanine(EG), were compared in the presence of calf thymus DNA and epoxide (VCO or NPO) in vitro system. The amounts of DNA adducts were decreased in the presence of GSH (25% and 29% in VCO, 32% and 29% in NPO), and NAC (14% and 16% in VCO, 21% and 11% in NPO), respectively. From these results, it is concluded that the ultimate carcinogenic metabolites, VCO and NPO, can be made in the body, but much of them may be inactivated and detoxified by the nucleophilic GSH, NAC and detoxifying enzymes (epoxide hydrolase and GST). Therefore, by these mechanism, the formation of DNA adducts and mutagenic activities of these two epoxides may be lowered in vivo.

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THE ESSENTIAL ROLE OF PI3-KINASE IN THE INDUCTION OF GLUTATHIONE S-TRANSFERASE BY TERT-BUTYLHYDROQUINONE AND OLTIPRAZ: DIFFERENTIAL EFFECTS ON Nrf2/ARE ACTIVATION

  • Kim, Sang-Geon;Kang, Keon-Wook
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.05a
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    • pp.96-106
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    • 2001
  • The phase II detoxifying enzymes are inducible by a variety of compounds and play an essential role for the protection of cells. Many of chemoprotective agents trigger cellular signals for the phase II enzyme induction, which subsequently activate gene transcription through ARE activation.(omitted)

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