• Environmental Analysis Health and Toxicology
• /
• 제3권3_4호
• /
• pp.39-51
• /
• 1988

Effects of ${\alpha}$-tocopherol and perilla oil on the toxicity of polychlorinated biphenyls (PCB) in male rat were studied. Rats were fed ad libitum for 6 weeks with the animal diet which contains PCB 30 ppm and 100 ppm. Perilla oil (0.5 g/kg body weight) and ${\alpha}$-tocopherol (30 mg/kg body weight) were administered intraperitoneally twice a week for 6 weeks. Rats fed with PCB showed enlargement of liver and spleen, increase in aspartate aminotransferase, alkaline phosphatase, sereum lipid and cytochrome P 450 and decrease in body weight and glutathione. When perilla oil was administered to rats fed with PCB increase in aspartate aminotransferase, alkaline phosphatase, serum lipid and cytochrome P45O and decrease in body weight and glutathione were significantly augmented, compared to rats fed with PCB alone. This means that perilla oil potentiates the toxicity of PCB. On the other hand when ${\alpha}$-tocopherol was administered to rats fed with PCB increase in aspartate aminotransferase, alkaline phosphatase, serum lipid and cytochrome P45O and decrease in body weight and glutathione were signigicantly reduced, compared to rats fed with PCB alone. This means that u-tocopherol reduces the toxicity of PCB. From the above results, it may be concluded that PCB is metabolized by microsomal mixed function oxidase and the metabolite causes the toxicity and microsomal glutathione plays a role of protection on the toxicity of PCB.

• 한국식품영양과학회지
• /
• 제23권4호
• /
• pp.561-567
• /
• 1994

This study was designed to evaluate the effects of dietary vitamin E and caffeine on the activities of lipid peroxidation related enzymes in rat liver . Male Sprague-Dawley rats were fed on diets containing three level of vitamin E (37.5, 750 or 1,5oomg/kg diet) and with or without 0.3% caffeine. The rats were sacrificed after 5 and 10 weeks of feeding. Results obtained from this study were as follows ; The content of cytochrome P450 tended to increase as dietary vitamin E level was raised. The activity of xanthine oxidase increased in the caffeine groups, but it decreased by the increasing level of vitamin E. Superoxide dismutase and catalase activity were slightly elevated by dietary supplementation of vitamin E. And there was a tendency of higher these enzyme activity of caffeine groups. The activity of glutathione perxidase tended to decrease as dietary vitamin E level increased. But it was raised by caffeine supplementation . Liver glutathione content was not affected by dietary supplementation of vitamin E, but it showed a decreasing tendency in caffeine groups. There was a tendency of more lipid peroxide content of caffeine groups than that of the only vitamin E supplemented group. But the degree of increment of this decreased as dietary vitamin E level increased.

• 동의신경정신과학회지
• /
• 제8권2호
• /
• pp.51-62
• /
• 1997

This experiment was done to investigate the antioxidant effect of Ondamtang(ODT) on brain tissues of rats. The experimental groups were divided into three groups and treated as follows for a fifteen days ; Negative control group(NC), Vitamin E admistrated group(PC), ODT administrated Group(ODT). After the extracting microsome from brain of rats, those were measured the amounts of Malondiadehyde and Hydrogen peroxide, then activities of antioxidant enzymes like Superoxide dismutase, Catalase and NADPH-cytochrome P-450 reductadse. The results were as follows; 1. In TBA reaction to measure the amount of MDA, oxidant material of brain tissue of rats, the group treated by ODT showed significant decrease. 2. In the formation of Hydrogen peroxide, the group treated by ODT showed no change in comparison with normal group. 3. The activity of SOD in the group treated by ODT showed a little increase in comparison with normal group. 4. The activity of Catalase was increased significantly in the group treated by ODT than normal group. 5. The activity of NADPH-cytochrome P-450 reductase in the group treated by ODT showed a little increase in comparison with normal group. According to the above results, it is suggested that Ondamtang(ODT) has some antioxidant effects on tissues of brain.

• Toxicological Research
• /
• 제13권3호
• /
• pp.257-263
• /
• 1997

Pentachlorophenol(PCP) which ks widely used in wood preservation, pulp and paper mills, has led to a substantial envirortmental contamination. To get the reliable data for the effective health risk assessment with PCP, covalent binding potential of PCP to cellular macromolecules and glutathione(GSH) was investigated after intraperitoneal administration of $^{14}C-PCP$ to rats. PCP metabolites were able to bind covalently to serum albumin and hepatic protein in a dose- and time-dependent manner. Hepatic protein adducts of PCP metabolites were increased as a function of cytochrome P-450 activities, whereas, albumin adducts significantly decreased. Covalent binding of PCP metabolites with DNA or hemoglobin was not observed. GSH levels in liver tissue decreased over 12hrs, however, the level was recovered after 48hrs. Tetrachloro-1,4-benzoquinone (1,4-TCBQ), one of the most reactive PCP metabolites, conjugated with GSH very rapidly. Base on our results, we could conclude that PCP metabolized to reactive electrophilic metabolites by cytochrome P-450 isoenzymes and conjugated rapidly with neighboring protein or nonprotein sulfhydryl before reacting with DNA or hemoglobin. We propose that albumin adducts and mercapturic acids of PCP metabolites can be used good biomarker of recent PCP exposure.

• 약학회지
• /
• 제28권1호
• /
• pp.53-59
• /
• 1984

Drug-metabolizing system which has the important role in drug metabolism is localized in smooth endoplasmic reticulum of hepatocytes and is composed of NADPH, NADPH-cytochrome $P_{450}$ reductase, cytochrome $P_{450}$ and others. It is well known that the enzyme system is induced by phenobarbital and methylcholanthrene. Lipid peroxidation is reaction of oxidative deterioration of polyunsaturated lipids. Formation of lipid peroxides in liver microsome has been found to produce degradation of phospholipid, which are major components of microsomal membrane. The relationship between the formation of lipid oxides and the activities of drug-metabolizing enzyme in the liver of rats was reported by several investigators. In this study the effect of riboflavin tetrabutylate, an antioxidant on lipid peroxidation, specially the relationship between lipid peroxidation and drug-metabolizing enzyme system was investigated. In addition the effect of vitamin A derivatives, such as retinoic acid and retinoid on the enzyme was also observed. Results are summarized as followings. 1) The pretretment with riboflavin tetrabutylate inhibited completely the lengthened sleeping time due to $CCl_{4}$ treatment. 2) The increase of TBA value was prevented by the pretreatment with riboflavin tetrabutylate. 3) The pretreatment with riboflavin tetrabutylate also prevented the decrease of drug-metabolizing enzyme caused by $CCl_{4}$. 4) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity.

• Applied Biological Chemistry
• /
• 제39권1호
• /
• pp.77-83
• /
• 1996

이스라엘 잉어에 있어서 carbamate계 살충제 carbofuran의 독성에 미치는 phenobarbital sodium(PB) 또는 3-methylcholanthrene (3-MC)의 영향과 작용기작을 효소적 측면에서 구명할 목적으로 carbofuran과 PB나 3-MC를 이스라엘 잉어에 각 조합으로 처리하여 독성경감 효과를 조사하였고, 공시한 농약과 PB나 MC가 acetylcholinesterase(AChE), glutathione S-transferase(GST), UDP-glucuronosyltransferase(UDPGT) 및 cytochrome P-450-dependent monooxygenase(monooxygenase)의 효소활성에 미치는 영향을 조사하기 위하여 carbofuran과 PB나 3-MC를 각각 조합으로 처리한 후 경시적으로 이스라엘 잉어의 각 효소들의 상대활성도를 조사하였다. PB와 3-MC만 투여한 실험군에서 이스라엘 잉어의 생존수는 무처리군과 동일하였고 살충제만 처리한 실험군의 이스라엘 잉어 생존수는 처리농도가 증가하면서 감소되었으나, PB나 3-MC와 살충제를 조합처리한 실험군에서는 살충제만 처리한 실힘군에 비하여 매우 높은 생존율을 나타낸 것으로 보아 해독효과가 인정 되었다. 효소활성(in vivo)은 AChE의 경우 carbofuran 0.95 ppm만을 처리한 실험군에서는 24시간내내 각 조사시기마다 무처리군에 비해 40% 이상의 활성저해를 보였으나 carbofuran과 PB 및 3-MC를 조합처리한 실험군에서는 효소활성이 초기에 감소하다가 서서히 증가하여 24시간후에는 무처리군과 비슷한 수준을 나타냈고, GST의 경우 carbofuran만을 처리한 실험군에서는 초기에 약 20% 이상의 활성저해를 보였으나 carbofuran과 PB나 3-MC를 조합처리한 실험군에서는 약제처리 1시간 후 부터 무처리군에 비해 효소활성이 20% 이상 증가하였다. UDPGT와 monooxygenase의 효소활성은 carbofuran과 PB나 3-MC를 조합처리한 실험에서 처리 $6{\sim}12$시간 후에는 carbofuran 처리군에 비해 효소활성이 $4{\sim}8$배 이상 급격히 높아졌다. 이상의 결과에서 PB 및 3-MC처리가 이들 효소의 활성을 유도함으로써 carbofuran의 독성으로 부터 이스라엘 잉어를 보호 하는데 관여한 것으로 보인다.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.411.1-411.1
• /
• 2002

The purpose of this study was to investigate the effect of quercetin on the bioavailability of paclitaxel orally coadministered in rats Paclitaxel is reported to be metabolized by cytochrome p-450(CYP3.A,)in both the liver and epithelial cells of small intestine and also absorption of paclitaxel is inhibited by p-glycoprotein efflux Pump in the intestinal mucosa. This resulted in poor orall bioavailability of paclitaxel. Area under the plasma concentration-time curve (AUC) of paclitaxel in combination with quercetin were significantly (p＜ 0.01) higher than those of control. (omitted)

• 동의신경정신과학회지
• /
• 제9궈1호
• /
• pp.45-57
• /
• 1998

The effect of HWANSODAN(HSD), on the level of brain antioxidants was examined in aged rat. The experimental groups were divided into three groups and treated as follows ; normal group(negative control), Vt.E administrated Group(HSD). The purified microsome from brain tissue, those were measired the amounts of oxidant materials like Malonfialdehyde(MDA) and H2O2, then activities of antioxidants enzymes like superoxide dismutase, catalase, NADPH-cytochrome P-450 reductase.The results were as follows;1. In TBA reaction to measure the amount of MDA, HSD group and Vt.E group did not showed signigicant decrease.2. In the formation of Hydrogen peroxide, HSD group and Vt.E group showed a little increase.3. The activity of Superoxide dismutase was increased significantly in HSD group and Vt.E group.4. In the activity of Catalase, Vt.E group was increased significantly and HSD group a little increased. 5. The activity of NADPH-cytochrome P-450 reductase in the HSD group and Vt.E group showed significantly increase.According to the above results, it is suggested that HWANSODAN(HSD) has some antioxidant effects on the tissue of brain.

• 동의신경정신과학회지
• /
• 제9궈1호
• /
• pp.59-71
• /
• 1998

The effect of Samyonjihwangtang(SJT) on th level of brain antioxidants was examined in aged rat. Samyongjihwangtang(SJT) is assed Cervi Pantiri-chum Cornu, Ginseng Radix to Yukmijihwangtang. The experimental groups were divided into three groups and treated as follows ; normal group(NC), Vt.E administrated group(PC), SJT administrated Group(SJT). From the purified microsome of brain tissue, those were measures the amounts of oxidant materials like malonaldehyde(MDA) and H_2O_2, then activities of antioxidants enxymes like Superoxide dismutase, Catalase, NADPH-cytochrome P-450 reductase.The results were as follows;1. In TBA reaction to measure the amount of MDA, oxidant material of brain tissue of aged rat, both treated groups showed significant decrease.2. In the formation of Hydrogen peroxide, the treated group(SJT) showed a little decrease.3. The activity of Superoxide dismutase was increased significantly in both treated groups than normal group.4. the activity of Catalase was increased significantly in both treated groups than normal group. 5. The activity of NADPH-cytochrome P-450 reductase in the treated group(SJT) showed a little increase.According to the above results, it is suggested that Samyongjihwangtag(SJT) has some antioxidant effects on the tissue of brain.

• Mass Spectrometry Letters
• /
• 제7권4호
• /
• pp.106-110
• /
• 2016

Ginseng, a traditional herbal drug, has been used in Eastern Asia for more than 2000 years. Various ginsenosides, which are the major bioactive components of ginseng products, have been shown to exert numerous beneficial effects on the human body when co-administered with drugs. However, this may give rise to ginsenoside-drug interactions, which is an important research consideration. In this study, acassette assay was performed the inhibitory effects of 12 ginsenosides on seven cytochrome P450 (CYP) isoforms in human liver microsomes (HLMs) using LC-MS/MS to predict the herb-drug interaction. After incubation of the 12 ginsenosides with seven cocktail CYP probes, the generated specific metabolites were quantified by LC-MS/MS to determine their activities. Ginsenoside Rb1 and F2 showed strong selective inhibitory effect on CYP2C9-catalyzed diclofenac 4'-hydroxylation and CYP2B6-catalyzed bupropion hydroxylation, respectively. Ginsenosides Rd showed weak inhibitory effect on the activities of CYP2B6, 2C9, 2C19, 2D6, 3A4, and compound K, while ginsenoside Rg3 showed weak inhibitory effects on CYP2B6. Other ginsenosides, Rc, Rf, Rg1, Rh1, Rf, and Re did not show significant inhibitory effects on the activities of the seven CYPs in HLM. Owing to the poor absorption of ginsenosides after oral administration in vivo, ginsenosides may not have significant side effects caused by interaction with other drugs.