• Journal of Food Hygiene and Safety
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• v.15 no.3
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• pp.226-234
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• 2000

Protective effect of Corydalis ternata against the carbon tetrachloride-induced toxicity was investigated. Carbon tetrachloride($CCl_4$) induces hepatotoxicity due to the reactive free radical(CCl$_3$ . ) generated by cytochrome P-450 enzyme. We examined effects of hexane, chloroform, butanol and water fractions prepared from the Corydalis ternata methanol extract. Rats were treated with those for 3 days, and liver microsomes and cytosols were prepared at 24 hour after last treatment. Hepatoprotective activity of the water fraction was higher than that of other fractions. To examine mechanism of the hepatoprotective effect of Corydalis ternuta, we measured contents of malondialdehyde(MDA), cytochrome P46O(CYP), glutathione, calcium as well as the activities of NADPH-CYP reductase, glutathione S-transferase(GST), superoxide dismutase(SOD), glutathione peroxidase(GPX) and catalase. The fraction inhibited production of MDA, content of CYP and calcium in liver of water fractions - treated rats as compared with those of CCl4-treated rats. The GST activity was increased. We speculate that the O2 radical scavenging activities of the water fraction might play a key role in the mechanism opposing the progression of $CCl_4$-induced hepatotoxicity, but the activities of SOD, GPX, CAT were decreased. These results suggest that the mechanism might be mainly due to the decrease of CYP contents, act as calcium channel blocker and increase of GST activity rather than $O_2$ radical scavenging activities.

• Preventive Nutrition and Food Science
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• v.5 no.4
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• pp.213-218
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• 2000

The purpose of the study was to investigate the effects of dietary green tea catechin and vitamin E on the phospholipse {TEX}$A_{2}${/TEX} activity and th antioxidative defense system in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats weighing 100$\pm$10 gm were randomly assigned to one normal and five STZ-induced diabetic groups. The diabetic groups were assigned either a catechin-free diet (DM group), 0.5% catechin diet (DM-0.5C group), 1% catechin diet (DM-1C group), vitamin E-free diet (DM-0E group), and 400 mg vitamin E per kg diet (DM-400E group) according to the levels of dietary catechin or vitamin E supplementation. The vitamin E levels of the normal, DM, DM-0.5C, and DM-1C groups were 40 mg per kg diet. Diabetes was experimentally induced by an intravenous injection of streptozotocin after 4 weeks of feeding the five experimental diets. The animals were sacrificed on the 6th day of he diabetic state. The body weight gains were lower in all five diabetic groups after the STZ injection. The platelet phospholipase {TEX}$A_{2}${/TEX}({TEX}$PLA_{2}${/TEX}) activity in the diabetic groups was higher than that in the normal group. However, the enzyme activity in the DM-0.5C, DM-1C, and DM-400E groups was lower than that in the DM and DM-0E groups. The cytochrome {TEX}$P_{450}${/TEX} and cytochrome {TEX}$b_{5}${/TEX} content and NADPH-cytochrome {TEX}$P_{450}${/TEX} reductase activity were about 50~110% higher in the DM and DM-0E groups than in the normal group, yet significantly reduced by either catechin or vitamin E supplementation. The superoxide dismutase (SOD) content in the liver did not differ significantly in any of the groups. However, the glutathione peroxidase (GSHpx) activity was generally lower in the diabetic groups, compared with the normal group, whereas that of the DM-0.5C, DM-1C, and DM-400E groups was significantly higher compared with that of the DM and DM-0E groups. The levels of thiobarbituric acid reactive substances (TBARS) in the liver tissue were 148% and 201% higher in the DM and DM-0E groups, respectively, compared with the normal group, however, these levels were reduced by either catechin or vitamin E supplementation (DM-0.5, DM-1C and DM-400E). Accordingly, the present results indicate that STZ-induced diabetic rats exhibited an imbalance between free radical generation and scavenger systems in the liver which led to the acceleration of lipid peroxidation. However, these abnormalities were reduced and the antioxidative defense system was restored by either dietary catechin or vitamin E supplementation. In conclusion, the effects of dietary catechin or vitamin E in streptozotocin-induced diabetic rats would appear to inhibit lipid peroxidation as an anti-oxidant by regulating the activity of {TEX}$PLA_{2}${/TEX}.

• Preventive Nutrition and Food Science
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• v.19 no.4
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• pp.268-273
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• 2014

The induction of detoxification enzymes by benzyl isothiocyanate (BITC) and its synthetic N-acetyl-L-cysteine (NAC) conjugate (NAC-BITC) was examined in Hepa1c1c7 murine hepatoma cells. BITC and NAC-BITC inhibited Hepa1c1c7 cell growth in a dose-dependent manner. Cell growth was 4.5~57.2% lower in Hepa1c1c7 cells treated with $0.1{\sim}1.0{\mu}M$ BITC than in control-treated Hepa1c1c7 cells. The NAC-BITC treatment had a similar inhibitory pattern on Hepa1c1c7 cell growth; $0.5{\mu}M$ and $10{\mu}M$ NAC-BITC decreased cell growth by 13.6% and 47.4%, respectively. Treatment of Hepa1c1c7 cells with $0.1{\sim}2.0{\mu}M$ BITC also elicited a dose-response effect on the induction of quinone reductase quinone reductase (QR) activity and QR mRNA expression. Treatment with $1{\mu}M$ and $2{\mu}M$ BITC caused 1.8- and 2.8-fold inductions of QR mRNA, respectively. By comparison, treatment with $1{\mu}M$ and $2{\mu}M$ NAC-BITC caused 1.6-and 1.9-fold inductions of QR mRNA, respectively. Cytochrome P450 (CYP) 1A1 and CYP2E1 induction were lower in $0.1{\sim}2{\mu}M$ BITC-treated cells than in control-treated cells. CYP2E1 activity was 1.2-fold greater in $0.1{\mu}M$ NAC-BITC-treated cells than in control-treated cells. However, the CYP2E1 activity of cells treated with higher concentrations (i.e., $1{\sim}2{\mu}M$) of NAC-BITC was similar to the activity of control-treated cells. Considering the potential of isothiocyanatesto prevent cancer, these results provide support for the use of BITC and NAC-BITC conjugates as chemopreventive agents.

• Preventive Nutrition and Food Science
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• v.9 no.1
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• pp.53-57
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• 2004

The purpose of this study was to investigate the effects of green tea catechin on mixed function oxidase system (MFO), lipofuscin contents, carbonyl value, oxidative damage and the antioxidative defense system in lung of microwave exposed rats. Experimental groups were divided to normal group and microwave exposed group. The microwave exposed groups were subdivided into three groups: catechin free diet (MW-0C) group, 0.25% catechin (MW-0.25C) group and 0.5 ％ catechin (MW-0.5C) group according to the levels of dietary catechin supplementation. The rats were irradiated with microwave at frequency of 2.45 GHz for 15 min. Experimental animals were sacrificed at 6th day after microwave irradiation. The contents of cytochrome P$_{450}$ contents in MW-0C group was increased to 95% , compared with normal group. MW-0.25C and MW-0.5C groups were reduced to 16% and 31%, respectively, compared with MW-0C group. The activity of NADPH-cytochrome P$_{450}$ reductase in MW-0C group was increased to 44%, compared with normal group. MW-0.25C and MW-0.5C groups were reduced to 12% and 17％, respectively, compared with MW-0C group. The activity of superoxide dismutase (SOD) in MW-0C group was decreased to 21 ％, compared with normal group. MW-0.25C and MW-0.5C group were significantly (p < 0.05) increased, compared with MW-0C group. The activity of glutathione peroxidase (GSHpx) in MW-0C group was significantly decreased, compared with normal group. MW-0.25C and MW-0.5C groups were recovered to the level of normal group. The thiobarbituric acid reactive substances (TBARS) content in MW-0C group was increased to 34 ％, compared with normal group. Catechin supplementation groups were maintained the level of normal group. The levels of caybonyl value in MW-0C group was increased to 21 ％, compared with normal group. MW-0.25C and MW-0.5C groups were reduced to 14% and 12%, respectively, compared with MW-0C group. The lipofuscin contents in MW-0C group were increased to 23.4 ％, compared with normal group. That of MW-0.5C group was significantly reduced, compared with MW-0C group. In conclusion, MFO system was activated and the formation of oxidized protein, lipofuscin was increased and antioxidative defense system was weakened of lung tissue in microwave exposed rats, thus oxidative damage was increased. But it was rapidly recovered to normal level by green tea catechin supplementation.n.

• Journal of Sasang Constitutional Medicine
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• v.16 no.3
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• pp.96-107
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• 2004

1. Objectives This study was carried out to investigate the effects of Gunyuljejo-tang on the $CCl_4$-induced Liver Damage in Rats. 2. Methods Sprague-Dawley rats were devided into 5 experimental groups : Normal, $NS+CCl_4$(Solid extract of $CCl_4$ injection group after Normal Saline feed), $GYJJT+CCl_4$(Solid extract of $CCl_4$ injection group after Gunyuljejo-tang feed), $CCl_4+NS$(Normal Saline feed group after $CCl_4$ injection), $CCl_4+GYJJT$(Solid extract of Gunyuljejo-tang feed group after $CCl_4$ injection). Biochemical assays for serum enzyme activities such as AST, ALT, ALP, BUN, Creatinine, Uric Acid, Total Protein, Albumin, Total Cholesterol, Triglyceride, Glucose, and mRNA Revelation of Cytochrome p450 and activities such as LPO, GSH, GST, Glutathione Reductase, Glutathione Peroxidase, SOD, Catalase, Hydroxyproline, and ${\beta}$-Glucuronidase were performed. 3. Results (1) $GYJJT+CCl_4$ showed lower revelation of Cytochrome p450. (2) $GYJJT+CCl_4$ showed higher GSH activity than $NS+CCl_4$, $CCl_4+GYJJT$ showed higher GSH activity than $CCl_4+NS$ injection significantly. (3) $GYJJT+CCl_4$ showed higher GST activity than $NS+CCl_4$. $CCl_4+GYJJT$ showed higher GST activity than $CCl_4+NS$ significantly. (4) $GYJJT+CCl_4$ showed higher Glutathione Peroxidase activity than $NS+CCl_4$, $CCl_4+GYJJT$ showed higher Glutathione Peroxidase activity than $CCl_4+NS$ significantly. (5) $CCl_4+GYJJT$ showed higher SOD activity than $CCl_4+NS$ significantly. (6) $CCl_4+GYJJT$ showed higher Catalase activity than $CCl_4+NS$ significantly. (7) $GYJJT+CCl_4$ showed lower Hydroxyproline than $NS+CCl_4$ significantly, $CCl_4+GYJJT$ showed higher Hydroxyproline than $CCl_4+NS$ significantly. (8) $GYJJT+CCl_4$ showed higher ${\beta}$-Glucuronidase activity than $NS+CCl_4$, $CCl_4+GYJJT$ showed higher ${\beta}$-Glucuronidase activity than $CCl_4+NS$ significantly. 4. Conclusions Gunyuljejo-tang has the recovering effects on the $CCl_4$-induced Liver Damage significantly.

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.31-35
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• 2020

Objective: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are frequently prescribed medications worldwide for the treatment of hypercholesterolemia. Statins are considered to be well tolerated; however, they have a potential for myotoxicity. Concomitant drugs that inhibit cytochrome P450 3A4 can increase the concentration of statins and thus the risk of developing myotoxicity. The purpose of this study was to evaluate risk factors associated with potential drug-drug interactions in patients receiving statins. Methods: The subjects of this study were patients aged more than 18 years who received at least one prescription of statins in a general hospital located in Chuncheon-si, Korea, between January 1, 2018, and March 31, 2018. Data regarding statin use and baseline characteristics was collected from the computerized hospital database. Logistic regression analysis was used to identify risk factors associated with potential drug-drug interactions. Results: A total of 1061 patients were finally included in the study. The incidence of potential drug-drug interactions was 45% in all subjects. According to the results of the multivariate logistic regression analysis, myocardial infarction as the indication of statin, arrhythmia or heart failure as a comorbidity, and aspartate aminotransferase levels higher than 40 IU/L were significant risk factors for potential drug-drug interactions in study subjects. Diltiazem was the most commonly co-prescribed drug that caused potential drug-drug interactions with statins. Conclusion: There was a considerable rate of potential drug-drug interactions in patients receiving statins. Health care professionals should attempt to reduce potential drug-drug interactions during statin administration.

• Journal of Microbiology and Biotechnology
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• v.31 no.3
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• pp.464-474
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• 2021

Bacterial cytochrome P450 (CYP) enzymes are responsible for the hydroxylation of diverse endogenous substances with a heme molecule used as a cofactor. This study characterized two CYP154C3 proteins from Streptomyces sp. W2061 (CYP154C3-1) and Streptomyces sp. KCCM40643 (CYP154C3-2). The enzymatic activity assays of both CYPs conducted using heterologous redox partners' putidaredoxin and putidaredoxin reductase showed substrate flexibility with different steroids and exhibited interesting product formation patterns. The enzymatic characterization revealed good activity over a pH range of 7.0 to 7.8 and the optimal temperature range for activity was 30 to 37℃. The major product was the C16-hydroxylated product and the kinetic profiles and patterns of the generated hydroxylated products differed between the two enzymes. Both enzymes showed a higher affinity toward progesterone, with CYP154C3-1 demonstrating slightly higher activity than CYP154C3-2 for most of the substrates. Oxidizing agents (diacetoxyiodo) benzene (PIDA) and hydrogen peroxide (H2O2) were also utilized to actively support the redox reactions, with optimum conversion achieved at concentrations of 3 mM and 65 mM, respectively. The oxidizing agents affected the product distribution, influencing the type and selectivity of the CYP-catalyzed reaction. Additionally, CYP154C3s also catalyzed the C-C bond cleavage of steroids. Therefore, CYP154C3s may be a good candidate for the production of modified steroids for various biological uses.

• Preventive Nutrition and Food Science
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• v.16 no.2
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• pp.95-103
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• 2011

This study was performed to investigate the antioxidant mechanism of tomato wine with varying lycopene content in rats fed a high fat diet (HFD). Male Sprague-Dawley rats were randomly divided into five groups (n=10 per group) and fed an HFD (35% of total energy from fat) plus ethanol (7.2% of total energy from alcohol), tomato wine with varying lycopene content (0.425 mg%, 1.140 mg% or 2.045 mg% lycopene) or an isocaloric control diet for 6 weeks. Mice fed HFD plus ethanol significantly increased erythrocyte hydrogen peroxide and thiobarbituric acid reactive substances (TBARS) levels with increases in activities of erythrocyte antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) compared to pair-fed rats. Supplementation of tomato wine with varying lycopene content decreased ethanol-mediated increases of erythrocyte lipid peroxidation and antioxidant enzyme activities in HFD-fed rats, and tomato wine with higher lycopene appeared to be more effective. Tomato wine also dose-dependently lowered TBARS levels with decreased pro-oxidant enzyme, xanthine oxidase (XOD) activity in plasma of HFD-fed rats. In contrast to erythrocytes, the inhibitory effects of tomato wine on hepatic lipid peroxidation were linked to increased hepatic antioxidant enzymes (SOD and CAT) and alcohol metabolizing enzyme (alcohol dehydrogenase and aldehyde dehydrogenase) activities. There were no significant differences in hepatic XOD and cytochrome P450-2E1 activities among the groups. Together, our data suggest that tomato wine fortified with lycopene has the potential to protect against ethanol-induced oxidative stress via regulation of antioxidant or pro-oxidant enzymes and alcohol metabolizing enzyme activities in plasma, erythrocyte and liver.

• Environmental Analysis Health and Toxicology
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• v.14 no.3
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• pp.87-93
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• 1999

Antioxidative and scavenging effects were investigated by using two hyaroxycinnamic acids (caffeetannins). such as caffeic acid and chlorogenic acid, on oxidative stress and hepatotoxicity that induced by paraquat. The results are summerized as follows: 1. To assess radical scavenging ability, reduction concentration (IC$\sub$50/) of 1.1 diphenyl-2-dipicrylhydrazine (DPPH) were measured. IC$\sub$50/ values of caffeic acid and chlorogenic acid were 29.7 ${\pm}$0.6 ${\mu}$M and 26.0${\pm}$0.5 ${\mu}$M respectively. Their radical scavenging activities showed concentration-dependent manner. 2. In H$_2$O$_2$-induced hemolysis assay to rat blood, caffeic acid and chlorogenic acid led to different effects, whose hemolysis inhibition ratios at 100 ${\mu}$M were 45.2${\pm}$7.1% and 11.6${\pm}$3.1% respectively 3. In hypoxanthine-xanthine oxidase system producing superoxide anion, caffeic acid and chlorogenic acid showed different inhibitory activities of xanthine oxidase showing 36.8${\pm}$4.3% and 5.4${\pm}$2.3% respectively. 4. To microsomal NADPH dependent cytochrome p-450 reductase in rat liver, paraquat consumed NADPH at a dose-dependent manner from 0 to 1 ${\mu}$M paraquat concentration. Caffeic acid and chlorogenic acid blocked NADPH consumption rates at concentration-dependent manner and inhibition ratios at 100 ${\mu}$M were 67.6% and 59.2% respectively. 5. Administration (30mg/kg, iv) of paraquat to rats caused the marked elevation of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and lipid peroxides (LPO) in the serum and lipid peroxides in the microsome as compared to the control group. Serum GOT, GPT, LDH, ALP and LPO and liver microsomal LPO were reduced significantly by caffeic acid (50mg/kg), chlorogenic acid (25mg/kg) and silymarin (150 mg/kg) as compared to the paraquat group. From these results, caffeic acid and chlorogenic acid exerted their antioxidative agents by removing reactive oxygen substance (ROS) and scavenging effects by inhibiting ROS generating enzyme. As a general, two hydroxyeinnamic acids showed the useful compounds for scavenger and reducer on the paraquat induced hepatotoxicity.

• YAKHAK HOEJI
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• v.52 no.4
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• pp.316-321
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• 2008

The hepatoprotection by the methanol extract of Oenanthe javanica DC (water dropwort) (OJME) was investigated in Sprague Dawley rats with inducing liver damage by acetaminophen. After OJME administration for 1 week, the increase of hepatic lipid peroxide level by acetaminophen-induced hepatotoxicity was significantly reduced. In case of phase I microsomal enzyme systems including cytochrome P-450, aminopyrine N-demethylase and aniline hydroxylase, any significant differences between in control and in OJME-pretreated group was observed after acetaminophen treatment. However, the pretreatment of OJME maintained the hepatic glutathione level and the activity of liver cytosolic glutathione S-transferase, which was significantly decreased by the acetaminophen intoxication. Among the glutathione-generating system, glutathione reductase was more responsible for its biosynthesis rather than ${\gamma}-glutamylcystein$ synthetase. OJME itself showed the strong inhibition activity on DPPH radical generation. In conclusion, OJME administration maintains the liver glutathione pool and hepatic glutathione S-transferase activity, in addition with its high anti-oxidative capability, to show hepatoprotective effect from acetaminophen intoxication.