• Asian-Australasian Journal of Animal Sciences
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• v.19 no.7
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• pp.1033-1039
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• 2006

The metabolic response of Labeo rohita to thermal acclimation was assessed. Advanced fingerlings of L. rohita (average weight $31{\pm}1.4g$) were acclimated to 31, 33 and $36^{\circ}C$ compared with ambient temperatures ($26^{\circ}C$) for 30 days and different enzymes associated with stress response were estimated. Glycolytic enzyme-Lactate dehydrogenase, (LDH, E.C.1.1.1.27), TCA cycle enzyme-Malate dehydrogenase (MDH, E.C.1.1.1.37), Protein metabolizing enzymes-Aspartate amino transferase (AST, E.C.2.6.1.1) and Alanine amino transferase (ALT, E.C.2.6.1.2) of liver, gill and muscle, Gluconeogenic enzymes-Fructose 1,6 Bi phosphatase (FBPase, E.C. 3.1.3.11) and Glucose 6 phosphatase (G6Pase, E.C. 3.1.3.9) of liver and kidney were significantly (p<0.05) different with increasing acclimation temperatures. Heat Shock Protein-70 (HSP-70) was expressed in increasing intensity at 31, 33 and $36^{\circ}C$ but was not expressed at $26^{\circ}C$. Results suggest that higher acclimation temperatures enhance metabolism and L. rohita maintains homeostasis between $26-36^{\circ}C$ via an acclimation episode. Such adaptation appears to be facilitated by resorting to gluconeogenic and glycogenolytic pathways for energy mobilization and induction of HSPs.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.749-755
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• 2014

Background: Purple rice has become a natural product of interest which is widely used for health promotion. This study investigated the preventive effect of purple rice extract (PRE) mixed diet on DMH initiation of colon carcinogenesis. Materials and Methods: Rats were fed with PRE mixed diet one week before injection of DMH (40 mg/kg of body weight once a week for 2 weeks). They were killed 12 hrs after a second DMH injection to measure the level of $O^6$-methylguanine and xenobiotic metabolizing enzyme activities. Results: In rats that received PRE, guanine methylation was reduced in the colonic mucosa, but not in the liver, whereas PRE did not affect xenobiotic conjugation, with reference to glutathione-S-transferase or UDP-glucuronyl transferase. After 5 weeks, rats that received PRE with DMH injection had fewer ACF in the colon than those treated with DMH alone. Interestingly, a PRE mixed diet inhibited the activity of bacterial ${\beta}$-glucuronidase in rat feces, a critical enzyme for free methylazoxymethanol (MAM) release in the rat colon. These results indicated that purple rice extract inhibited ${\beta}$-glucuronidase activity in the colonic lumen, causing a reduction of MAM-induced colonic mucosa DNA methylation, leaded to decelerated formation of aberrant crypt foci in the rat colon. Conclusions: The supplemented purple rice extract might thus prevent colon carcinogenesis by the alteration of the colonic environment, and thus could be further developed for neutraceutical products for colon cancer prevention.

• Journal of Microbiology and Biotechnology
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• v.25 no.1
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• pp.18-25
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• 2015

To understand the metabolism of flavonoid rhamnoglycosides by human intestinal microbiota, we measured the metabolic activity of rutin and poncirin (distributed in many functional foods and herbal medicine) by 100 human stool specimens. The average α-L-rhamnosidase activities on the p-nitrophenyl-α-L-rhamnopyranoside, rutin, and poncirin subtrates were 0.10 ± 0.07, 0.25 ± 0.08, and 0.15 ± 0.09 pmol/min/mg, respectively. To investigate the enzymatic properties, α-L-rhamnosidase-producing bacteria were isolated from the specimens, and the α-L-rhamnosidase gene was cloned from a selected organism, Bifidobacterium dentium, and expressed in E. coli. The cloned α-L-rhamnosidase gene contained a 2,673 bp sequcence encoding 890 amino acid residues. The cloned gene was expressed using the pET 26b(+) vector in E. coli BL21, and the expressed enzyme was purified using Ni²⁺-NTA and Q-HP column chromatography. The specific activity of the purified α-L-rhamnosidase was 23.3 µmol/min/mg. Of the tested natural product constituents, the cloned α-L-rhamnosidase hydrolyzed rutin most potently, followed by poncirin, naringin, and ginsenoside Re. However, it was unable to hydrolyze quercitrin. This is the first report describing the cloning, expression, and characterization of α-L-rhamnosidase, a flavonoid rhamnoglycosidemetabolizing enzyme, from bifidobacteria. Based on these findings, the α-L-rhamnosidase of intestinal bacteria such as B. dentium seem to be more effective in hydrolyzing (1 →6) bonds than (1 →2) bonds of rhamnoglycosides, and may play an important role in the metabolism and pharmacological effect of rhamnoglycosides.

• Toxicological Research
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• v.8 no.2
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• pp.265-272
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• 1992

Effects of repeated physical exercise on the carbon tetrachloride ($CCl_4$) hepatotoxicity were examined in adult female rats. Rats were introduced into a cylindrical rotating cage and forced to exercise for 1 hr each day, 6days/week, for 5 consecutive weeks at a speed starting from 10m/min, increased by 1m/min per day until the speed reached 27m/min. Significantly less body weight gain was observed in the exercise group suggesting that physical fitness had been induced in these animals. Eighteen hours following termination of the last exercise bout rats were treated with $CCl_4$(2 mmol/kg.ip). The $CCl_4$-induced heptotoxicity was significantly potentiated in the repeated exercise group compared to the resting sedentary animals as determined by changes in serum sorbitol dehydrogenase (SDH), glutamic oxaloacetic transaminase(GOT), glutamic pyruvic transaminase (GPT), and glucose-6-phosphatase(G-6-Pase) activities when measured 24hrs following the $CCl_4$ treatment. Hepatic drug metabolizing activity was determined in order to elucidate the underlying mechanism of potentiating action of the $CCl_4$ hepatotoxicity induced by repeated physical exercise. Repeated exercise increased the hepatic microsomal cytochrome P-450 contents and aminopyrine N-demethylase activity. The results suggest that the potentiation of $CCl_4$ hepatotoxicity by repeated exercise is associated with induction of the mixed function oxidase (MFO) enzyme system mediating the metabolism of $CCl_4$ to its active metabolite(s).

• Biomolecules & Therapeutics
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• v.8 no.4
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• pp.299-304
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• 2000

The modulation of cytochrome P450(P450) activities and glutathione S-transferase (GST) was investigated after i.p. administration of glucose-diethyldithiocarbamate (Glu-DDTC) to rats. P450 1 A2 and 2El activities were inhibited by 60% 4 hr after the administration of 200 mg Glu-DDTC/kg and those activities were recovered to original levels 24 hr after dosing. In contrast, GST activities were enhanced up to 24 hr after dosing. These results seem to be due to the bifunctional activity of Glu-DDTC. Glu-DDTC acts as an inhibitor of P450 enzymes as well as inducer of GST enzyme. Glu-DDTC inhibited PNP hydroxylation (P450 2El) and ethoxycoumarin O-deethylation (P450 1A2) in a dose-dependent manner up to 200 mg/kg wherease it did not affect testosterone 6$\beta$-hydroxylation (P450 3A) and pentoxyresorufin O-dealkylation (P450 2B) activities. Induction of GST activity toward 1-chloro-2,4-dinitrobenzene (CDNB) and 1,2-dichloro-4-nitrobenzenen (DCNB) was dependent on the dose of Glu-DDTC and no species difference in the GST induction was seen between rat and mouse. Amoung GST subunits, Ya, Yb1 and partially Yb2 were induced by Glu-DDTC as conjugated by western blotting. The levels Yp, Yk and Yc subunits were not affected by Glu-DDTC treatment. Therefore the enhanced activity of GST toward CDNB and DCNB might be due to the induction of Ya, Ybl and partially Yb2 subunits. In conclusion, Glu-DDTC selectively inhibited P45O 1A2 and P450 2El activities whereas it enhanced Ya, Ybl subunits and partially Yb2 subunits of GST and the antimutagenic activity of this compound might be attributed from the modulation of these enzyme activities in animals.

• Korean Journal of Environmental Biology
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• v.26 no.2
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• pp.109-114
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• 2008

To evaluate the extent of Sea-Nine 211 (4,5-dichloro-2-n-octyl-3(2H) isothiazolone), one of the alternating organic booster compound used in antifouling paint to replace TBT, on marine benthic bivalve, we injected Sea-Nine 211 to clam, Pseudocardium sachalinensis, and then determined some xenobiotics metabolizing enzyme activities, especially EROD (ethoxyresorufin deethylase) and MROD (methoxyresorufin demethylase), in digestive gland during 4 day-exposure period. Moreover, the results were compared with those of TBT exposed clam. CYP1A1 dependant EROD activity in both the Sea-Nine 211 and the TBTC exposure groups showed no significant differences compared to those of the solvent control group. CYP1A2 dependant MROD activity in Sea-Nine 211 exposure group was significantly induced, but no significant difference was obtained in the TBTC exposure group. These results indicate that Sea-Nine 211 demonstrated a tendency to induce MROD activity, while TBTC inhibits the activities of this enzyme.

• Journal of Pharmacopuncture
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• v.17 no.3
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• pp.16-24
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• 2014

Objectives: Alcohol abuse is a public issue and one of the major causes of liver disease worldwide. This study was aimed at investigating the protective effect of Ganoderma lucidum pharmacopuncture (GLP) against hepatotoxicity induced by acute ethanol (EtOH) intoxication in rats. Methods: Sprague-Dawley (SD) rats were divided into 4 groups of 8 animals each: normal, control, normal saline pharmacopuncture (NP) and GLP groups. The control, NP and GLP groups received ethanol orally. The NP and the GLP groups were treated daily with injections of normal saline and Ganoderma lucidum extract, respectively. The control group received no treatment. The rats in all groups, except the normal group, were intoxicated for 6 hours by oral administration of EtOH (6 g/kg BW). The same volume of distilled water was administered to the rats in the normal group. Two local acupoints were used: Qimen (LR14) and Taechung (LR3). A histopathological analysis was performed, and the liver function and the activities of antioxidant enzymes were assessed. Results: GLP treatment reduced the histological changes due to acute liver injury induced by EtOH and significantly reduced the increase in the alanine aminotransferase (ALT) enzyme; however, it had an insignificant effect in reducing the increase in aspartate aminotransferase (AST) enzyme. It also significantly ameliorated the superoxide dismutase (SOD) and the catalase (CAT) activities. Conclusion: The present study suggests that GLP treatment is effective in protecting against ethanol-induced acute hepatic injury in SD rats by modulating the activities of ethanol-metabolizing enzymes and by attenuating oxidative stress.

• Preventive Nutrition and Food Science
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• v.12 no.4
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• pp.202-208
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• 2007

Persimmon is well-known as a Korean traditional medicine for alleviating coughs and enhancing blood circulation; it is also used for treatment of hypertension, cancer, diabetes and atherosclerosis. To evaluate the protective properties of persimmon leaf methanol extract (PLME) and persimmon fruit methanol extract (PFME) administration on acute ethanol-induced hepatotoxicity, C57BL/6 male mice were gavaged with or without persimmon extracts for 1 week. Hepatotoxicity was then induced by gavage of 5 g/kg BW ethanol. After 12 hr of ethanol administration, blood and liver were collected and analyzed for biochemical markers of hepatotoxicity. The results showed PLME and PFME treatments decreased the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared with ethanol control. Both PLME and PFME reduced serum lactate dehydrogenase (LDH) activity, but elevated alcohol dehydrogenase (ADH) activity. Serum triglyceride (TG) and hepatic cholesterol levels were significantly decreased when treated with PLME and PFME. Liver malondialdehyde (MDA) levels were significantly decreased in PLME and PFME groups compared with ethanol control. Furthermore, the administration of PLME and PFME significantly increased the activities of catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-red). In summary, PLME and PFME appeared to prevent hepatic injury by accelerating alcohol metabolism by increasing alcohol-metabolizing enzyme activities, by activating the antioxidative enzyme system against oxidative stress, and by decreasing fat accumulation, which is evidenced by decreased hepatotoxic indices in serum.

• Journal of the Korean Society of Food Science and Nutrition
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• v.18 no.3
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• pp.239-246
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• 1989

Preventive effect of azalea pollen extracts against aniline-induced hepatic toxicity in mice was investigated in this experiment. When the biochemical and histological changes were measured, preventive effect was more striking by treatment with water extract. After treatment with azalea pollen extracts, hepatic microsomal aniline hydroxylase activity increased as compared to control. Whereas, aniline level in serum and liver significantly decreased. The Vmax value without affecting Km value increased by the water extract treatment, the results obtained suggest that the characteristics of increase in the aniline hydroxylase activity may include induction of enzyme proteins. These data indicate that the observed preventive effects of azalea pollen extracts against hepatotoxicity is due to the induction of aniline metabolizing enzyme.

• Korean Journal of Clinical Pharmacy
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• v.20 no.1
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• pp.25-29
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• 2010

The purpose of this study was to investigate the effect of atorvastatin on the pharmacokinetics of nifedipine (6 mg/kg) after oral administration of nifedipine with or without atorvastatin (0.5 and 2.0 mg/kg) in rats, and also was to evaluate to the effect of atorvastatin on the CYP3A4 activity. The 50% inhibiting concentration ($IC_{50}$) values of atorvastatin on CYP3A4 activity is 46.1 ${\mu}M$. Atorvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner. Coadministration of atorvastatin increased significantly (p<0.05, 2.0 mg/kg) the plasma concentration-time curve (AUC) and the peak concentration ($C_{max}$) of nifedipine compared to the control group. The relative bioavailability (RB%) of nifedipine was increased from 1.15- to 1.37-fold. Coadministration of atorvastatin did not significantly change the terminal half-life ($T_{1/2}$) and the time to reach the peak concentration ($T_{max}$) of nifedipine. Based on these results, we can make a conclusion that the significant changes of these pharmacokinetic parameters might be due to atorvastatin, which possesses the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein (P-gp) efflux pump in the intestinal mucosa. It might be suggested that atorvastatin altered disposition of nifedipine by inhibition of both the first-pass metabolism and P-glycoprotein efflux pump in the small intestine of rats. In conclusion, the presence of atorvastatin significantly enhanced the oral bioavailability of nifedipine, suggesting that concurrent use of atorvastatin with nifedipine should require close monitoring for potential drug interation.