• Archives of Pharmacal Research
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• 제27권7호
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• pp.693-712
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• 2004

The rats with protein-calorie malnutrition (PCM, 5％ casein diet for a period of 4-week) were reported to exhibit 60 and 80％ suppression in the hepatic microsomal cytochrome P450 (CYP) 1 A2 and CYP2C11 levels, respectively, and 40-50％ decreases in CYP2E1 and CYP3A 1/2 levels compared to control (23％ casein diet for a period of 4-week) based on Western blot analysis. In addition, Northern blot analysis showed that CYP1 A2, CYP2E1, CYP2C11, and CYP3A1/2 mRNAs decreased in the state of PCM as well. Hence, pharmacokinetic changes of the drugs in rats with PCM [especially the area under the plasma concentration-time curve from time zero to time infinity (AUC) changes of metabolite(s)] reported from literatures were tried to explain in terms of CYP isozyme changes in the rats. Otherwise, the time-averaged nonrenal clearance ($CL_{NR}$) of parent drug was compared. Pharmacokinetic changes of the drugs in other types of malnutritional state, such as kwashiorkor and marasmus, in both human and animal models were also compared. The drugs reviewed are as follows： diuretics, antibiotics, anticancer agents, antiepileptics, antiarrythmics, analgesics, xanthines, antimalarials, and miscellaneous.

• Toxicological Research
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• 제4권1호
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• pp.13-22
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• 1988

The inhibitory effect of three polyacetylene compounds, panaxydol, panaxynol and panaxytriol isolated from Panax ginseng C.A. Meyer on $CCl_4$induced lipid peroxidation in vivo and in vitro hepatic microsomal lipid peroxidation induced by ADP-$Fe^{3+}$, NADPH and NADPH-cytochrome P-450 reductase were investigated. Their effects on lowering the lipid peroxide levels both in serum and liver and lowering the serum enzyme (GOT, GPT, LDH) activities without the $CCl_4$-induction were also determined. Male ICR mice were pretreated i.p. with polyacetylene compounds or DL-${\alpha}$-tocopherol before administration of $CCl_4$ i.p. and 20 hr after the administration of $CCl_4,$ serum and liver were analyzed. Hepatic microsome was isolated and used for the in vitro NADPH-dependent lipid peroxidation system. Except for panaxynol, treatment with polyacetylenes to control mice did not reduce the levels of lipid peroxides and serum enzyme activities. Panaxynol itself inhibited lipid peroxidation in the liver of normal mice. Polyacetylene compounds protected from the $CCl_4$-induced hepatic lipid peroxidation and lowered serum lipid peroxide levels. Polyacetylenes also inhibited the in virto hepatic microsomal lipid peroxidation in a dose-dependent manner. The results suggest that panaxydol, panaxynol and panaxytriol seem to be the antioxidant components which contribute the anti-aging activities of Panax ginseng C.A. Meyer.

• Environmental Analysis Health and Toxicology
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• 제9권1_2호
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• pp.9-17
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• 1994

The Ha-antagonist, cimetidine, has been shown to retard the hepatic elimination of low and high clearance drugs, and this has been attributed to inhibition of microsomal cytochrome P-450. This study was done to determine the effects of low (50$\mu\textrm{g}$) and high (1mg) dose of famotidine, another histamine H$_2$-receptor antagonist, on hepatic elimination of propranolol compared with cimetidine in the isolated perfused rat liver. Both low and high dose of cimetidine not only inhibited the elimination of propranolol but also increased the area under the perfusate propranolol concentration time curve (AUC). In contrast, low and high dose of famotidine did not affect hepatic elimination of propranolol. Our findings suggest that famotidine has not a propensity for hepatic microsomal inhibition.

• 한국식품영양과학회지
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• 제20권3호
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• pp.203-208
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• 1991

The present study was undertaken in order to elucidate the effects of pretreatment with nicotinamide on changes in the hepatic metabolizing enzyme system inducted by streptozotocin (STZ). In rats, STZ(50mg/kg) administered by tail vein caused a significant rise in hepatic aniline hydroxylase and a decrease in aminopyrine N-demethylase when compared to control (p<0.05). Pretreatment with nicotinamice inhibited these effects (p<0.05). Similarly, STZ induced changes in hepatic microsomal cytochrome P-450 activity were inhibited by pretreatment with nicotinamide (p<0.05). However, changes in UDP-glucuronyl transferase and sulfortransferase activity were not significantly different(p>0.05). Pretreatment with nicotinamide also prevented STZ induced increases in glutathion S-tranferase activity when compared to the control(p<0.05). There results suggest that nicotinamide pretreatment suppresses STZ-induced changes in the hepatic metabolizing enzyme system.

• 한국식품영양과학회지
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• 제23권5호
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• pp.725-730
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• 1994

This study was conducted to investigate the effect of dietary zinc (Zn) and/or cadmium (Cd) on hepatic microsomal and cytosol enzyme activities. Male Spraque-Dawley rats (110$\pm$10g ) received zinc (0, 30 and 300 ppm/) and Cd-treated groups were administered oral intubation with Cd chloride (5.0mg/kg of body weight 0 at the same time once a week. The effect of Cd on the activity of hepatic cytochromep-450 , xanthine oxidase(X. O) and superoxide dismutase (SOd) was studied in rats. Cd oral intubation resulted in a decrease in cytochrome P-450 content and SOD activity whereas a significant increase in the X.O. activity was observed was observed . Intake of excessive Zn led to an increased activity of microsomal alcohol dehydrogenase (ADH) , whereas Zn deficiency group led to a decreased group. The mechanism by which Zn induces the decreasing of Cd toxicity in rats, seems to rely on the protection of the enzyme systems P-450, ADH, aldehyde dehydrogenase (ALDH) and X.O. in the liver, possibly by forming non-toxic Cd metallothionein. These results indicate that Zn and Cd regulation might occur via inhibitory protein component of the $H_2O$$_2$ -generator system.

• Archives of Pharmacal Research
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• 제28권12호
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• pp.1386-1391
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• 2005

This study examined the role of Kupffer cells in altering the hepatic secretory and microsomal function during ischemia and reperfusion (ls/Rp). Rats were subjected to 60 min of hepatic ischemia, followed by 1 and 5 h of reperfusion. Gadolinium chloride ($GdCl_{3}$, 7.5 mg/kg body weight, intravenously) was used to inactivate the Kupffer cells 1 day prior to ischemia. Is/Rp markedly increased the serum aminotransferase level and the extent of lipid peroxidation. $GdCl_{3}$ significantly attenuated these increases. Is/Rp markedly decreased the bile. flow and cholate output, and $GdCl_{3}$ restored their secretion. The cytochrome P450 content was decreased by Is/Rp. However, these decreases were not prevented by $GdCl_{3}$. The aminopyrine N-demethylase activity was decreased by Is/Rp, while the aniline p-hydroxylase activity was increased. $GdCl_{3}$ prevented the increase in the aniline p-hydroxylase activity. Overall, Is/Rp diminishes the hepatic secretory and microsomal drug-metabolizing functions, and Kupffer cells are involved in this hepatobiliary dysfunction.

• Biomolecules & Therapeutics
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• 제5권1호
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• pp.59-66
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• 1997

This study was done to determine that vitamins I and C are synergistic in protecting liver cells during hepatic ischemia and repefusion. Rats treated with vitamins I and C were subjected to 60 min of hepatic ischemia and to 1 and 5 hr of reperfusion thereafter. Serum aminotransferase level and microsomal lipid peroxidation were markedly increased by ischemia/reperfusion. These increases were significantly attenuated by vitamins E, C or its combination. Hepatic wet weight-to-dry weight ratio was increased in ischemic group, but this increase was prevented by combination of vitamin I and C. Bile flow and cholate output were markedly decreased by ischemia/reperfusion and vitamin C alone and combination of vitamin I and C restored their secretion. Cytochrome P-450 content and aminopyrine N-demethylase activity were decreased by ischemia/ reperfusion and restored by vitamin C and combination of vitamin I and C to the level of sham-operated rat. Aniline p-hydroxylase activity was increased by ischemia/reperfusion and this increase was prevented by vitamin E. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory and microsomal functions by increasing lipid peroxidation and vitamins I and C synergistically ameliorates these changes.

• 분석과학
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• 제5권1호
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• pp.83-90
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• 1992

$^{14}C$-warfarin을 흰쥐에 경구투여 후 4시간 경과시 혈액에서 최고치를 나타내었으며, coumarin과 그 유도체인 warfarin에 의한 간조직 microsome 내의 Cyt. p-450은 이들 화합물에 의해 microsomal electron transport system이 증가됨과 Cyt. p-450의 isozyme들이 유도됨을 확인할 수 있었다.

• 한국식품영양과학회지
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• 제29권1호
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• pp.168-173
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• 2000

The purpose of this study was to investigate the changes of microsomal mixed function oxidase (MFO) and xanthine oxidase activities (XOD) in the liver of rats exposed to microwave. Sprague-Dawley male rats weighing 200$\pm$10g body weight were randomly assigned to a normal and microwave exposed(MW) groups; microwave exposed groups were divided into two groups; microwave (MW) group and green tea(GT) gropu which were fed distilled water and green tea extracts during experimental periods, respectively. Rats were irradiated with microwave at the frequency of 2.45 GHz for 15min and rats wre sacrificed at the 4th day of the microwave irradiaton. The hemoglobin level of GT group was higher than that of the normal gropu and MW group, but the hematocrit value was not significantly different among all experimental gropus. The activity of serum GOT of MW group was significantly increased but that of GT group was similar to normal group. Activities of GPT were not significantly different among all experimental groups. Liver XOD activity was significantly increased in the microwave exposed groups but green tea normalized the XOD activity. The activity of hepatic microsomal cytochrome P450 was significantly increased in MW group compared to normal group and that of GT group was similar to that of the normal group. The activity of hepatic microsomal NADPH-cytochrome P450 reductase was also significantly increased in MW group compared to normal group, but that of GT group was similar to that fo the normal group. In conclusion, the activities of MFO and XOD were elevated by microwave irradiaton, but the activation of MFO system as well as the damage of the liver by microwave were reduced by green tea supplementation.

• 생약학회지
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• 제28권4호
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• pp.280-285
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• 1997

Pectenotoxin 2 (PTX2), isolated from marine sponges, was examined for its hepatotoxic potential using male ICR mice. PTX2 $(20\;or\;100\;{\mu}g/kg/day,\;ip)$ was administered to mice repeatedly for one or two week. Histopathological examination revealed an increase in granularity in the liver from the mice treated with PTX2. PTX2 did not alter the parameters for hepatotoxicity and nephrotoxicity such as sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and blood urea nitrogen (BUN). Cytochrome P-450, cytochrome $b_5$, or NADPH cytochrome c reductase was net changed by repeated administration of PTX2. Hepatic microsomal activity of p-nitroanisole O-demethylase, but not aminopyrine N-demethylase, was slightly depressed by PTX2 administerd repeatedly $(100\;{\mu}g/kg/day,\;ip)$ fur 2 weeks. The toxicity of PTX2 $(200\;{\mu}g/kg/day,\;ip)$ was determined in mice pretreated with a metabolic inducer or inhibitor such as phenobarbital, 3-methyl-cholanthrene, $CoCl_2$, or SKF 525-A. Significant alterations in lethality and hepatotoxicity of PTX2 were observed in mice pretreated with a metabolic modulator. The results suggest that liver seems to be the target organ for PTX2 toxicity and also that induction of the PTX2 toxicity may be associated with hepatic drug metabolizing activity.