• Title/Summary/Keyword: CYP450 1A1

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Mycelial Culture of Lentinus edodes Alleviates Rat Liver Toxicity Induced by Carbon Tetrachloride and Ethanol (표고버섯균사체의 사염화탄소 및 알콜로 처리된 흰쥐 간기능 보호 효과)

  • Ha, Yeong-L.;Kim, Young-S.;Ahn, Chae-R.;Kweon, Jung-M.;Park, Cherl-W.;Ha, Young-K.;Kim, Jeong-O.
    • Journal of Life Science
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    • v.20 no.1
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    • pp.133-141
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    • 2010
  • The protective effect of a mixed powder from solid-cultured and liquid-cultured Lentinus edodes mycelia (2:1, w/w) (designate LED) on the carbon tetrachloride ($CCl_4$)- and ethanol-induced hepatotoxicity of male Sprague-Dawley (SD) rat was investigated. In the $CCl_4$-induced rat hepatotoxicity experiment, rats of 4 groups (6 rats/group) were administere with Normal (0.2 ml distilled water), Control (0.2 ml distilled water), LED (LED 200 mg/kg BW + 0.2 ml distilled water), and Silymarin (200 mg/kg BW + 0.2 ml distilled water), p.o., daily for 2 weeks. Afterwards, all groups except for the Normal group were subjected to abdominal injection with $CCl_4$ ($CCl_4$ : corn oil, 1:1 v/v; 0.5 ml/kg BW). For the ethanol- induced rat hepatotoxicity experiment, rats were divided into 5 groups (5 rats/group): Normal; Pair-fed control (PFC); Control (ethanol); LED (ethanol + LED 200 mg/kg BW); and Silymarin (ethanol + silymarin 200 mg/kg BW). Rats of the Normal and PFC groups were fed a basal liquid diet, and rats of the Control, LED, and Silymarin groups were fed a liquid ethanol diet containing LED or Silymarin. Eight weeks later, blood and liver samples were collected to analyze biomarkers. In $CCl_4$-induced SD rats, LED elevated hepatic superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH peroxidase) activities and thiobarbituric reactive substances (TBARS) were reduced, resulting in the reduction of glutamate-oxalate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and lactic dehydrogenase (LDH) activities in plasma. Similar results of these enzymes and biochemical markers in both liver tissues and plasma were seen in ethanol-induced hepatotoxicity of SD rats. In addition, elevated alcohol dehydrogenase (ADH) activity and reduced expression of cytochrome p450 mixed monooxygenase enzyme (CYP2E1) were seen in liver tissues from ethanol-treated rats by LED treatment. These effects of LED were similar to those of Silymarin. In in vitro experiments, LED showed antioxidant activity in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) system and mouse liver mitochondria system induced by NADPH/$Fe^{2+}$ and cumine hydroperoxide (CuOOH). These results indicate that LED protected SD rat hepatotoxicity, induced by $CCl_4$ and ethanol, through its antioxidative activity and might be useful as a material for protection from hepatoxicity in humans.

Use of Information Component (IC) and Relative Risk (RR) for Signal Detection of Drug Interactions of Clopidogrel : Data-mining Study Using Health Insurance Review & Assessment Service (HIRA) Claims Database (정보 성분과 상대위험도를 이용한 clopidogrel의 약물상호작용 시그널 검색 : 건강보험데이터베이스를 대상으로 한 데이터마이닝 연구)

  • Kim, Jin-Hyung;Choi, Chung-Am;Oh, Jung-Mi;Son, Sung-Ho;Shin, Wan-Gyoon
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.2
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    • pp.90-99
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    • 2011
  • Health Insurance Review & Assessment Service (HIRA) claims database has a high potential to detect signals of new drug interactions. The aim of this study was to evaluate the usefulness of information component (IC) and relative risk (RR) as a tool for signal detection, and to analyze the possible drug interactions caused by clopidogrel using HIRA claims database. This study was performed in elderly patients over 65 years of age who administered clopidogrel from January 2005 to June 2006 in South Korea. Serious Adverse Events (SAEs) as drug interactions of clopidogrel were defined as any ambulatory hospitalization for ischemic diseases within comcomitant medication period of clopidogrel. Information Component (IC) and Relative Risk (RR) were calculated to compare the proportion of drug-SAE pairs in order to select drug specific SAEs. IC and RR signals of clopidogrel drug interaction were screened when IC's 95% confidence interval was greater than 0 and RR's 95% confidence interval was greater than 1 respectively. All detected signals were compared to references such as $Micromedex^{(R)}$ and 2010 Drug Interaction $Facts^{TM}$. Sensitivity, specificity, positive predicted value and negative predicted value were used to evaluate usefulness of this method. Among 13,252,930 cases of elderly patients who co-administered clopidogrel and other drugs, 47,485 cases were detected as SAE. Of these, one-hundred nine cases were detected by the IC-based data-mining approach and ninety one cases were detected by the RR-based data-mining approach. Total One-hundred sixty three unrecognized signals were detected by IC or RR. Twelve signals from IC-based data-mining (57.1%) were corresponded with drug interactions from references and eight signals from RR-based data-mining (38.1%) were corresponded with drug interactions from references. These signals include proton pump inhibitors, calcium channel blockers and HMG CoA reductase Inhibitors, which were known to affect CYP450 metabolism. Further studies using HIRA claims database are necessary to develop appropriate data-mining measure.

Effect of Pine Needle Water Extract on Cadmium-Induced Oxidative Stress in Rats (솔잎 열수추출물이 카드뮴으로 유도한 흰쥐의 산화적 손상에 미치는 영향)

  • Jang, Joo-Yeun;Kim, Myung-Joo;Lee, Mi-Kyung;Kim, Duk-Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.4
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    • pp.411-418
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    • 2007
  • Oxidative stress can play a key role in cadmium (Cd)-induced dysfunction. The present study examined the effect of pine needle water extract (PN) on Cd-induced oxidative stress in rats. Sprague-Dawley male rats were divided into three groups: normal group, Cd control group (Cd) and PN-administered Cd group (Cd-PN). $CdCl_2$ in 0.9% NaCl was administered orally with a dose of 5mg/kg of body weight/week, while the PN was administered orally with a dose of 1.26g/kg of body weight/day. Body weight gain was not different between groups, whereas food intakes were significantly lower in the Cd-PN group than in normal or Cd group. Relative liver weight was significantly increased by cadmium administration compared to the normal group. Hepatic cytochrome P450 was significantly lower in Cd and Cd-PN groups than in normal group, while xanthine oxidase and alcohol dehydrogenase activities were significantly higher in the Cd-PN group than in normal or Cd group. Increased hepatic superoxide dismutase, monoamine oxidase, catalase, and glutathione peroxidase activities by cadmium administration were significantly decreased by PN supplement. PN did not affect the hepatic glutathione content in cadmium-administered rats; however, PN significantly lowered the hepatic lipid peroxide level and plasma alanine transferase activity compared to the Cd control group. These results suggest that the PN may alleviate Cd-induced oxidative stress without hepatotoxicity.

Effect of Glutathione S-Transferase Polymorphisms on the Antioxidant System (Glutathione S-Transferase 유전적 다형성이 항산화 체계에 미치는 영향)

  • Jeon, Gyeong-Im;Park, Eun-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.6
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    • pp.708-719
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    • 2007
  • Glutathione S-transferase genotypes GSTT1, GSTM1 and GSTP1 were characterized in 104 healthy male and female subjects and compared with parameters of oxidative stress at the level of DNA and lipids, with antioxidant enzymes, and with plasma antioxidants in smokers and non.smokers. Of the 104 subjects studied, 57.4% were GSTT1 present and 47.6% were GSTM1 present. The GSTP1 polymorphisms a and b were represented as follows: a/a, 75.5%; a/b, 21.6%; b/b type, 2.9%. The GSTT1 null genotype was associated with decreased glutathione in erythrocytes and elevated lymphocytes DNA damage. GST-Px was higher in GSTT1 null compared with GSTT1 present type. The homozygous GSTP1 genotype was not associated with any antioxidant status or DNA damage. The difference in plasma ${\alpha}$-carotene and erythrocytes GSH-Px and GST activities between smokers and non-smokers was detected in the GSTT1 null genotype. Plasma ${\gamma}$-tocopherol and ${\beta}$-carotene decreased significantly in smokers having GSTM1 null genotype. When GSTT1 and GSTM1 were combined, plasma lycopene and erythrocyte GST were reduced in smokers in both null types of these genes. As for GSTP1 genotype, plasma ${\alpha}$-carotene and erythrocytes GSH-Px decreased significantly in smokers with GSTP1 b/b, while erythrocytes GSH-Px activities decreased in smokers with GSTP1 a/b. The different ${\beta}$-carotene level between smokers and non-smokers was seen with both GSTP1 a/a and a/b genotype. It seems that polymorphisms in the phase II metabolizing enzyme glutathione S-transferase may be important determinants of commonly measured biomarkers.