• Archives of Pharmacal Research
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• 제26권11호
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• pp.951-959
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• 2003

A series of typical (chlorpromazine, haloperidol and thioridazine) and atypical (risperidone, quetiapine, clozapine and olanzapine) antipsychotics were tested for effects on integrated bioenergetic functions of isolated rat liver mitochondria. Polarographic measurement of oxygen consumption in freshly isolated mitochondria showed that electron transfer activity at respiratory complex I is inhibited by chlorpromazine, haloperidol, risperidone, and quetiapine, but not by clozapine, olanzapine, or thioridazine. Chlorpromazine and thioridazine act as modest uncouplers of oxidative phosphorylation. The typical neuroleptics inhibited NADH-coenzyme Q reductase in freeze-thawed mitochondria, which is a direct measure of complex I enzyme activity. The inhibition of NADH-coenzyme Q reductase activity by the atypicals risperidone and quetiapine was 2-4 fold less than that for the typical neuroleptics. Clozapine and olanzapine had only slight effects on NADH-coenzyme Q reductase activity, even at 200 $\mu$ M. The relative potencies of these neuroleptic drugs as inhibitors of mitochondrial bioenergetic function is similar to their relative potencies as risk factors in the reported incidence of extrapyramidal symptoms, including tardive dyskinesia (TD). This suggests that compromised bioenergetic function may be involved in the cellular pathology underlying TD.

• Preventive Nutrition and Food Science
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• 제8권2호
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• pp.158-161
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• 2003

This study investigated the effects of a ${\gamma}$-irradiated pork (0-30 kGy) diet on lipid peroxidation, cytochrome P-450 content, microsomal glucose 6-phosphatase (G-6-Pase) activity and antioxidative defense systems in diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis. The body weight of rats fed irradiated diets did not change significantly. Liver weight was significantly increased by the administration of DEN, but not by irradiated diets at any dose level. There were no significant effects of gamma irradiation on the content of microsomal malondialdehyde (MDA), cytochrome P-450, or on the activity of G-6-Pase. However, with DEN treatment, cytochrome P-450 content was significantly increased while microsomal G-6-Pase activity was significantly decreased. The ${\gamma}$-irradiated diet supplement did not affect serum retinol or $\alpha$-tocopherol concentrations. However, it did cause a significant decrease in hepatic retinol at 30 kGy. With DEN treatment, hepatic retinol content was even more significantly (p<0.05) decreased compared to the non-irradiated control. The enzyme activities related to antioxidative defense systems, including glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rx) and glutathione S-transferase (GST) were not affected by gamma irradiation. Those results suggest that an irradiated pork diet up to 30 kGy may not cause a health hazard in experimental animals.

• Journal of Nutrition and Health
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• 제41권7호
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• pp.583-593
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• 2008

This study was designed to examine the effects of Salicornia herbacea L. (glasswort: GW) on hepatic antioxidative enzyme activities in diabetic rats. Diabetes mellitus was induced in male Sprague-Dawley rats weighing 200-220g by an injection of streptozotocin (STZ) dissolved in a citrate buffer into the tail vein at a dose of 45 mg/kg of body weight. Sprague-Dawley rats were fed an AIN-93 recommended diet and the experimental groups were fed a modified diet containing 10% and 20% of glasswort powder for 4 weeks. The experimental groups were divided into 6 groups which consisted of normal (N)-control group, N-GW 10% and N-GW 20% treated groups, STZ-control, STZ-GW 10% and STZ-GW 20% treated groups. The activities of Xanthine oxidase (XOD), glutathione- S-transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD) and CAT (CAT) were measured in the homogenates of liver. The activity of CAT was lower in the supplementary group with glasswort compare to the STZcontrol group but it was not significantly different. The activity of SOD was not significant in all of experimental groups. The activity of GR was significantly increased in the normal supplementary group with glasswort, and GPX activity was significantly increased in STZ-GW 10% group compare to the STZ-control group. The activity of XOD was significantly decreased in the all of supplementary groups with glasswort. The activity of GST was significantly increased in the N-GW 20% group and it was significantly decreased in the STZ-GW 20% group. These results show that the supplementation of glasswort may have favorable influence on antioxidative status in diabetic rats and it may be useful for the diabetic complications as functional food.

• The Korean Journal of Physiology
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• 제19권2호
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• pp.155-160
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• 1985

Dantrolene sodium(DS) is a long acting skeletal muscle relaxant which has been successfully used to control muscle spasticity in patients with various neurological disorders. However, its use is associated with hepatotoxicity. Tissue sulfhydryl group has many important roles for cellular integration and glutathione serves as a substrate for the detoxification metabolism. The purpose of this study were to investigate the effect of DS on tissue sulfhydrl group and glutathione content. Foully albino rats were divided into two groups ; saline treated (control) and DS treated groups. DS dissolved in saline was administered orally. All rats were sacrificed after 7. 14. 21 and 28 days of DS ana saline treatment by dacapitation ana liver was removed for the enzyme preparation. Total and nonprotein sulfhydryl were measured by the method of Sedlak and Lindsay (1968). Total glutathione content was assayed according to the method described by Tietze (1969) and glutathione reductase was assayed according to the method of Racker (1955), The results obtained are summarized as follows : DS administration significantly depressed the total, protein and nonprotein sulfhydryl content in liver. There were significant reduction of both total glutathione content and glutathione reductase activity in liver. On the basis of the above results it may be speculated that the toxicity of DS are well correlated with tissue sulfhydryl content and glutathione reductase activity.

• Biomolecules & Therapeutics
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• 제15권4호
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• pp.261-265
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• 2007

Hydroxyproline (HYP) is a post-translational product of proline hydroxylation catalyzed by an enzyme prolyl 4-hydroxylase (P4H) which plays a crucial role in the synthesis of all collagens. Considering the role of collagen and its significance in many clinically important diseases such as liver fibrosis, a great deal of attention has been directed toward the development of an assay at cell-based system. The reason is that cell-based assay system is more efficient than enzyme-based in vitro system and takes much less time than in vivo system. Several assay procedures developed for P4H are laborious, time-consuming and not feasible for the massive-screening. Here, we report the cell-based assay method of prolyl 4-hydroxylase in immortalized rat hepatic stellate HSC-T6 cells. To optimize the cell culture condition to assay for HYP content, various concentrations of reagents were treated for different times in HSC-T6 cells. Our data showed that the treatment with ascorbate in a hypoxic condition for 24 h resulted in the maximal increase of HYP by 1.8 fold. Alternatively, cobalt chloride ($5\;{\mu}M$) and ascorbate ($50\;{\mu}M$) in normoxic states exhibited similar effect on the production of HYP as in a hypoxic condition. Therefore, cobalt chloride can be substituted for a hypoxic condition when an anaerobic chamber is not available. Rosiglitazone and HOE077, known as inhibitors of collagen, synthesis decreased P4H enzyme activity by 32.3% and 15%, respectively, which coincided with previous reports from liver tissues. The level of the smooth muscle ${\alpha}$-actin, a marker of activated stellate cells, was significantly increased under hypoxia, suggesting that our experimental condition could work for screening the anti-fibrotic compounds. The assay procedure took only 3 days after treatment with agents, while assays from the primary stellate cells or liver tissues have taken several weeks. Considering the time and expenses, this assay method could be useful to screen the compounds for the inhibitor of prolyl 4-hydroxylase.

• 대한한방내과학회지
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• 제29권1호
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• pp.90-103
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• 2008

Objective : This study wascarried out to understand the effect of Sopyung-tang (SPT) on blood glucose & antioxidant enzyme activities in streptozotocin-induced diabetic rats. Methods : SD rats were separated into three groups, each with 20 rats. Except the normal group, the other two groups were intra-peritoneally injected with streptozotocin 6mg/kg. The experimental group was treated with SPT extract 500mgkg/day for 4 weeks. The normal and control groups were treated with saline 500mg/kg/day for 4 weeks. Changes of plasma glucose level and body weight were observed. After4 weeks, liver and kidney weight, antioxidant enzyme activities, and survival rate were observed with histological changes on liver, kidney and pancreas. Results : In the experimental group, body weight and survival rate increased, while plasma glucose level decreased significantly. Liver and kidney weight, XOD activity decreased in the experimental group compared to the control. GSH-px and CAT activities andinsulin-immunoreactive granules in ${\beta}-cells$ increased significantly in the experimental group compared to the control. Conclusions : This study shows that SPT might be effective for treatment of diabetes and its complications, as well as reduction of oxidative stress.

• Journal of Nutrition and Health
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• 제30권1호
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• pp.19-24
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• 1997

This study was carried out to investigate the effects of enzyme activities on male Sprague-Dawley rats intoxicated by CCI4 on IS(Godulbaegi) diets for 4 weeks. We divides into 5 diet groups which were normal diet(N), normal diet intoxicated by CCI4(NC) and 3 IS diets ; leaves diet(ILC), roots diet(IRC) and mixed diet of leaves and roots which were also injected by CCI4 3 times for 4 weeks. The activity of glutamic pyruvic transaminase(GPT) in serum in NC was higher than in N as we expected. The GPT activites and the values of malondial-dehyde(MDA) of IS groups were all lower than in NC, IC as lowest. The activity of superoxide dismutase(SOD) in NC was higher than in N and IS groups had values less than the values of N. Catalase showed similarity in results as above. The values of glutathione S-transferase(GST) and cytochrome P-450 in NC were lower than in N. IS groups had higher values than in NC. Godulbaegi might be important not only as one of the traditional Korean foods but also as therapeutic agent for hepatotoxicity and for shortening the recovery time in liver disease.

• 한국환경과학회지
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• 제27권11호
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• pp.999-1005
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• 2018

The purpose of this study was to probe the influences of krill (Euphausia superba) meal with NaF oral administration on a dose-effect relationship between fluoride levels of krill meal and serum enzyme activity such as alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in rats fed experimental diets for 5 weeks. There were no significant decreases in the activities of ALP, AST, ALT, and LDH in sera among krill meal diet groups (KF10, KF20, KF30). However, these groups were significantly (p<0.05) lower enzyme activities than normal diet (ND) plus NaF 10 mg group (NF). The fluoride levels of serum and organ tissues (liver, brain, heart, lung, kidney) in NaF 10 mg groups (NF, KF10, KF20, KF30) were significantly increased by adding krill meal in comparison with normal diet group. The results indicate that a difficult to found toxicity to the tissues from krill meal diet groups.

• Toxicological Research
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• 제19권2호
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• pp.105-114
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• 2003

TO evaluate an effect of cyclohexane treatment on the degree of liver damage, rats were induced liver damage with 10 or 17 times $CCl_4$ injection (0.1 m1/100 g body wt., 50% $CCl_4$ dis-solved in olive oil) at intervals of every other day. Cyclohexane (1.56 g/kg body wt., i.p.) was administrated to the animals at 48 hours after the last pretreatment of $CCl_4$ . Rats were sacrificed at 4 hours after injection of cyclohexane. On the basis of histopathological findings, liver weight/body weight (LW/ BW, %), activities of serum alanine aminotransferase (ALT), xanthine oxidase (XO) and akaline phosphatase (ALP), and contents of liver protein and manlondialdehyde (MDA), $CCl_4$ -pretreatment induced liver damage. And $CCl_4$ 17 times treated group showed more severe liver damage than $CCl_4$ 10 times treated group. Administration of one dose of cyclohexane to $CCl_4$ 10 times treated animals resulted in the enhanced liver damage; liver necrosis with proliferation of fibroblast and bile duct abnormality, and increase in hepatic MDA content and the activities of serum ALP and ALT, But the enhanced liver damage was not found in $CCl_4$ 17 times treated animals. Serum cyclohexanone concentrations at 4 or 8 hours after injection of cyclohexane were higher in all liver damaged groups than normal group and were somewhat higher In $CCl_4$ 17 times treated animals than $CCl_4$ 10 times treated ones. Among the oxygen free radical metabolizing enzymes, hepatic cytochrome P45O dependent aniline hydroxylase (CYPdAH) activity in cyclohexane metabolizing enzyme system was meaningfully increased by the injection of cyclohexane to the liver damaged rats, with increased Vmax and high affinity to aniline. LW/BW (%) and activities of serum XO and ALT were more significantly increased in liver damaged groups than normal group by administration of cyclohexanone. In conclusion, it is assumed that an enhancement of liver damage by injection of one dose of cyclohexane to liver damaged animals might be caused by oxygen free radicals and cyclohexanone.

• 대한수의학회지
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• 제37권2호
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• pp.383-388
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• 1997

카드뮴이 마우스의 효소활성에 미치는 영향을 평가하고자 BALB/c 마우스를 대상으로 0, 25, 50, 100 및 200 ppm의 $CdCl_2$가 첨가된 음료를 7주동안 자유급식한 후 간 및 신장에서 카드뮴(Cd)의 축적정도 및 효소(LDH 및 SOD)활성 변화를 조사하여 다음과 같은 결과를 얻었다. 1. 간 및 신장에서의 Cd축적도는 투여량이 증가될 수록 높았으며 특히 신장에서 더욱 높았다. 2. 간장과 신장의 lactate dehydrogenase(LDH)활성치는 신장의 경우 농도가 증가할 수록 활성치도 증가(25 ppm ; p<0.05, 50, 100 및 200 ppm; p<0.01)하는 경향을 보였으나 간에서는 100 ppm까지는 농도에 비례하여 활성치도 증가(50 및 100 ppm; p<0.05)하였다가 200ppm 투여군에서는 25 ppm 투여군 수준으로 감소되었다. 3. Superoxide dismutase(SOD)활성은 25 ppm 투여군의 간장에서 유의한 상승치(p<0.05)를 보인 것을 제외하고는 대조군의 간 및 신장의 활성치와 유사한 결과를 보였다. 이상의 결과는 카드뮴이 농도에 따라서 생체내의 LDH 및 SOD와 같은 효소계의 활성에 영향을 미칠 수 있음을 시사한다.