• Title/Summary/Keyword: liver metabolizing enzyme activities

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Sub-acute toxicity and effect of Hwangryunhaedok-tang on human drug-metabolizing enzymes

  • Jin, Seong Eun;Lee, Mee-Young;Seo, Chang-Seob;Shin, Hyeun-Kyoo;Cho, Jae-Woo;Ha, Hyekyung
    • The Journal of Korean Medicine
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    • v.38 no.2
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    • pp.15-30
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    • 2017
  • Objectives: Hwangryunhaedok-tang (HHT; Huanglianjiedu-tang, Orengedoku-to), a traditional herbal formula, is used for treating inflammation, hypertension, gastritis, liver dysfunction, cerebrovascular diseases, dermatitis and dementia. The objective of this study was to assess the sub-acute toxicity of HHT in Sprague-Dawley (SD) rats, and its effect on the activities of human microsomal cytochrome P450s (CYP450s) and UDP-glucuronosyltransferases (UGTs). Methods: Male and female SD rats were orally administered HHT once daily at doses of 0, 500, 1000 and 2000 mg/kg for 4 weeks. We analyzed mortality, clinical observations, body weight, food consumption, organ weights, urinalysis, hematology, serum biochemistry, and histopathology. The activities of major human CYP450s (CYP1A2, CYP3A4, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP2E1) and UGTs (UGT1A1, UGT1A4, and UGT2B7) were assessed using in vitro fluorescence- and luminescence-based enzyme assays, respectively. Results: No toxicologically significant changes related to the repeated administration of HHT were observed in both male and female SD rats. The no observed adverse effect level (NOAEL) value was more than 2000 mg/kg/day for both sexes. HHT inhibited the activities of human microsomal CYP1A2, CYP2C19, CYP2D6, and CYP2E1, whereas it weakly inhibited the activities of CYP2B6, CYP2C9, CYP3A4, and UGT1A1. In addition, HHT negligibly inhibited the activities of human microsomal UGT1A4 and UGT2B7 with $IC_{50}$ values in excess of $1000{\mu}g/mL$. Conclusions: Our findings indicate that HHT may be safe for repeated administration up to 4 weeks. In addition, these findings provide information on the safety and effectiveness of HHT when co-administered with conventional drugs.

Hepatic Oxygen Free Radical Metabolizing Enzyme Activities and Serum Lipid Profile in Rats Fed Diet Supplemented with Monascus Pigment (흰쥐에 있어서 홍국 첨가 식이가 혈청 지질성분 및 간조직의 유해산소 대사효소활성에 미치는 영향)

  • 유대식;김현희;윤종국
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.2
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    • pp.244-249
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    • 2003
  • To investigate the hepatic oxygen free radical metabolizing system and changes of serum cholesterol levels in rats fed a diet supplemented with Monascus pigment (MP), Sprague-Dawley rats weighing about 300 g have been fed a diet supplemented with 2% or 4% MP for a month. The rats fed 2% MP supplemented diet gained less body weight than the control rats and those fed 4% W supplemented diet. Those fed 2% or 4% MP supplemented diet had no remarkable changes in liver function on basis of liver weight/body weight, serum levels of xanthine oxidase, alanine amino transferase activity In rats fed 2% and 4% MP supplemented diet, hepatic cytochrome P45O dependent aniline hydroxylase activity significantly (p<0.05) declined about 32%, 37% respectively and showed no significant differences between rats fed 2% and 4% MP supplemented diet whereas those fed 2% MP supplemented diet showed about 29% increased hepatic xanthine oxidase activity. And hepatic glutathione S-transferase and glutathione peroxidase activites in rats fed 2% MP supplemented were more increased by about 17%, 28% respectively than the control rats. There were no significant differences both in between those fed 2% and 4% MP supplemented diet. Especially rats fed 2% or 4% MP supplemented diet showed a significant (p<0.05) increase in hepatic catalase activity by 41%, 25% compared with control rats and those fed 4% MP supplemented diet showed more decrease in tendency of catalase activity than those 2% MP supplemented diet. But hepatic superoxide dismutase activity and glutathione content were appeared to be similar value among three groups. On the other hand, rats fed 2% MP supplement diet showed 17% increased levels of serum HDL-choresterol and 26% decreased value of LDL-cholesterol and serum level of triglyceride. But no different value were appeared between those fed 2% and 4% MP supplemented diet. Especially in those fed 2% and 4% MP supplemented diet, artherogenic index were significantly (p<0.05) declined by 37%, 29% respectively compared with control. In conclusion, it is likely that rats fed a diet supplemented with a proper quantity of MP may have the potential of oxygen free radical detoxication and lowering of artherogenic index.

Effect of Dietary Protein and Fiber on Ethanol-induced Hepatotoxicity in Rats (흰쥐의 에탄올성 간장해에 미치는 식이 단백질과 섬유소의 영향)

  • 조수열;박은미;이미경;장주연;김명주
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.4
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    • pp.675-681
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    • 1997
  • This study was conducted to investigate the effect of dietary protein and fiber levels on the activities of ethanol metabolizing enzymes of liver in ethanol-treated rats. Sprague-Dawley male rats were fed on diets containing two levels of protein(7, 20%/kg diet) and pectin(5, 10%/kg diet). In ethanol experiments, ethanol(25% v/v) was administered by oral intubation(5g/kg body weight) at the same time once a day Control animals received an isocaloric dose of sucrose. The rats were sacrificed after 5 weeks of feeding periods. Alcohol dehydrogenase and microsomal ethanol oxidizing system activities of hepatic tissue were increased more in ethanol-treated groups than in control groups. Increment of activities predominated in normal protein normal fiber group. Aldehyde dehydrogenase activity was decreased in ethanol-treated groups and significantly decreased in normal Protein normal fiber group. Cytochrome P-450 content was significantly increased in ethanol-treated groups and Predominated in normal protein groups. Xanthine oxidase activity was increased in ethanol-treated groups, but not significantly except normal protein normal fiber group. Glutathione content tended to increase in proportion to level of dietary protein and was higher in normal fiber groups than in high fiber groups, whereas it was decreased by ethanol treatment. Lipid Peroxide content was significantly increased in low Protein normal fiber groups.

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Effects of Cudrania Tricuspidata Root Extract (CTE) on Ethanol-Induced Hangover via Modulating Alcohol Metabolizing Enzyme Activities and Blood Gas Levels in Rats (꾸지뽕나무 뿌리 추출물의 알코올 대사 효소 활성 및 혈액 산성화 기전 조절을 통한 숙취해소 효과)

  • Choi, Na-Eun;Ro, Ju-Ye;Lee, Ju-Yeong;Ryu, Jin-Hyeob;Cho, Hyun-Jeong
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.18 no.2
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    • pp.218-225
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    • 2017
  • To investigate the anti-hangover effects of Cudrania tricuspidata root extract (CTE), the blood alcohol metabolism and blood gas imbalance of CTE in rats treated with 10 ml/kg alcohol were examined. CTE (500 mg/kg and 750 mg/kg) was administrated after 30 minutes of alcohol consumption (10 ml/kg). Blood collection was implemented from the tails of the animals after 1, 3, and 5 hours post alcohol consumption. The Condition drink (a commercial anti-hangover beverage) was used as a positive control. Single administration by the oral route was performed. The consumption of CTE (500 mg/kg and 750 mg/kg) decreased the serum alcohol concentration by increasing and maintaining both the alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) enzyme activity levels in the blood and liver. In addition, CTE led to recovery from the imbalances in the blood gas levels, including carbon dioxide ($CO_2$) and changes in pH, bicarbonate ($HCO_3{^-}$) and lactic acid levels due to alcohol ingestion. In conclusion, CTE exerted a more pronounced anti-hangover effect than a commercial anti-hangover drink. Therefore, CTE can be a novel and safe anti-hangover natural product agent for the prevention or treatment of symptoms caused by excessive alcohol consumption.

Effect of Butylated Hydroxytoluene and 2-Acetylaminofluorene Administration and Microsomal Mixed Function Oxidase System in Young Rats fed different Fats (Butylated Hydroxytoluene첨가 식이 및 2-Acetylaminofluorene 투여가 식이지방을 달리한 쥐간의 Microsomal Mixed Function Oxidase계에 미치는 영향)

  • 윤은영
    • Journal of Nutrition and Health
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    • v.23 no.1
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    • pp.11-18
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    • 1990
  • Sprague-Dawley male rats were fed the diet of p/s 4.0(soybean oil : I), p/s 0.08(Beef tallow : II) at the level of 15% fat until 8 weeks after weaning. I & II groups were divided into 4 sub-groups by diets with or without 0.3% butylated hydroxytoluene(BHT). 2-AAF was injected at the age of $5_{1/2}$, 6, $5_{1/2}$, 7 weeks. MFO system enzyme(cytochrome p-450, cytochrome p-450 reductase, cytochrome b5) activities and lipid peroxide were determined from isolated liver microsome. 2-AAF injected young rats had growth retardatiion. Lipid peroxide values were not influenced greatly by dietary fat, 2-AAF and BHT. Cytochrome p-450 contents were increased in I-BHT-AAF & II-AAF groups by 2-AAF and its contents were not affected by BHT. But cytochrome p-450 and cytochrome p-450 reductase were not increased in soybean oil diet ybean oil groups. Cytochrome b5 was not influenced by dietary fat, 2-AAF and BHT. Cytochrome p-450 and lipid peroxide, cytochrome p-450 reductase and cytochrome b5, which transfer to MFO system, appeared to have positive correlations(r=0.2474, r=0.2475, p<0.05) each other. This result suggests that MFO system metabolizing 2-AAF was influenced by dietary fats and BHT. 2-AAF induced growth retardation in young rats.

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Inhibition of Drug-metabolizing Enzyme and Drug Transporter by Major Components of Phellodendri cortex (황백의 주요 구성 화합물에 의한 약물대사효소 및 약물수송단백 저해능 평가)

  • Ku, Hei-Young;Kim, Hyunmi;Shon, Ji-Hong;Liu, Kwang-Hyeon
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.3
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    • pp.213-217
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    • 2006
  • We evaluated the potential of major components of Phellodendri cortex to inhibit the activities of CYP2D6 and p-glycoprotein. The abilities of berberine, palmatine, limonin, and rutaecarpine to inhibit CYP2D6-mediated dextromethorphan O-demethylation and calcein AM accumulation were tested using human liver microsomes and L-MDR1 cell, respectively. Berberine strongly inhibited CYP2D6 isoform activity, whereas limonin and reuaecarpine did not. The $IC_{50}$ value of berberine was reduced after preincubation with microsomes in the presence of NADPH generating system, suggesting that berberine is a mechanism based inhibitor. In addition, all chemicals tested, didn't show inhibitory effect on p-glycoprotein activity. These results suggest that berberine has potential to inhibit CYP2D6 activity in vitro. Therefore, in vivo studies investigating the interactions between berberine and CYP2D6 substrates are necessary to determine whether inhibition of CYP2D6 activity by berberine is clinically relevant.

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Effect of Alcohol Detoxification Beverage that Contained Bulnesia sarmienti on Alcohol-metabolizing Enzymes and Antioxidant Enzyme Activities (Bulnesia sarmienti 를 함유한 숙취해소 음료가 알코올대사 및 항산화 효소활성에 미치는 영향)

  • Lim, Ae-Kyung;Jung, Mee-Jung;Lee, Jae-Wook;Hong, Joo-Heon;Kim, Kil-Soo;Jung, Seok-Bang;Kim, Dae-Ik
    • Food Science and Preservation
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    • v.18 no.3
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    • pp.407-413
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    • 2011
  • This study was carried out to investigate the effect of a beverage that contained Bulnesia sarmienti(BSP, 2.5%) on rats to which alcohol was administered. The treatment of the BSP group reduced the serum alcohol concentration to 52%, compared to 47% in the positive control(PC) group. Similar pattell1s were observed in the enhancement of alcohol dehydrogenase(ADH), acetaldehyde dehydrogenase(ALDH), alkaline phosphate(ALP), alanine aminotransferase(ALT), asparate aminotransferase(AST), total cholesterol(CHOL), ${\gamma}$-glutamyltrasferase(GGT), glucose(GLU), total bilirubin, and total protein(TP) in the serum. Also, in the BSP group, the lipoxidase(LPO), glutathion-S-transferase(GST), XO, catalase(CAT), and superoxide dismutase(SOD) were significantly reduced, compared to the CO and PC groups in the liver. The glutathione(GSH) activity increased in the BSP group, though. These results indicate that Bulnesia sarmienti extract can enhance alcohol metabolization activity.

Evaluation of the Effects of Hangover-Releasing Agent Containing Vinegar Extract in Common Buckwheat and Tartary Buckwheat on Alcohol Metabolism and Hangover Improvement (일반메밀과 쓴메밀의 식초 추출물의 알코올 대사 및 숙취개선 효능 평가)

  • Su Jeong Kim;Hwang Bae Sohn;A Hyun Park;Jong Nam Lee;Su Hyoung Park;Jung Hwan Nam;Do Yeon Kim;Dong Chil Chang;Yul Ho Kim
    • Korean Journal of Plant Resources
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    • v.36 no.5
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    • pp.435-445
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    • 2023
  • The aim of this study was to explore the effects of vinegar extract from seed of common buckwheat (Fagopyrum esculentum Moench) and seed of tartary buckwheat (F. tataricum Gaertner) on acute ethanol-induced hangover in Sprague-Dawley rats. Vinegar extract from buckwheat is rich choline, quercetin and its glycoside, rutin known as flavonoid antioxidants. The test extract containing buckwheat was proven to alleviate hangovers through a significant reduction in the concentration of alcohol and acetaldehyde in the context of an alcohol-induced hangover model. Hepatic alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities were significantly higher in buckwheat vinegar-treated rats than in ethanol-treated rats. Moreover, tartary buckwheat vinegar upregulated antioxidant enzyme such as superoxide dismutase and Catalase activities in liver tissues. These results suggest that buckwheat vinegar extract could alleviate ethanol-induced hangover symptoms by elevating activities related to hepatic ethanol-metabolizing enzymes against ethanol induced metabolites, and in particular, tartary buckwheat should be further developed to be a novel anti-hangover material.