• Journal of Environmental Health Sciences
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• v.29 no.2
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• pp.23-28
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• 2003

To evaluate the effect of cyclohexane(CH) treatment on the liver cytochrome P-450 dependent aniline hydroxylase(CYPdAH) activity in alcohol-pretreated animals, CH(1.56 g/kg body weight) was intraperitoneally administered to Sprague-Dawley male rats, which had been drunk 15％ alcohol in distilled water for 1,3 and 6 weeks. CH was injected to rats 4 times every other day and the animals were sacrificed at 24 hours after injection of CH. In the alcohol-pretreated rats, liver injuries were not demonstrated on the basis of the liver weight per body weight, the levels of serum alanine aminotransferase and hepatic microsomal glucose-6-phosphatase activities. By the CH treatment, alcohol-pretreated animals showed the significantly increased activity of hepatic microsomal CYPdAH. Concomitantly $V_{max}$ value in CYPdAH was more increased, whereas $K_{M}$ value more decreased in alcohol-pretreated animals by the treatment of CH. In conclusion, the increasing cause of microsomal CYPdAH in CH-treated rats pretreated with alcohol may be due to induction of enzyme protein in rat liver.r.r.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.6
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• pp.859-866
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• 1995

This study was done to investigate the effects of chronic ethanol feeding on hepatic microsomal cytochrome system, lipid peroxidation and peroxide metabolizing enzyme activities in 2-acetylaminofluorene(2-AAF) treated rats. Male Sprague-Dawley rats, weighing 120~125g, were pair-fed liquid diets containing 35% of total calories either as ethanol or isocaloric carbohydrates for 6 weeks. After 4 weeks of experimental diet feeding, 2-AAF(100mg/kg body weight) was injected twice a week intraperitoneally. Both weight and percent liver weight per body weight were significantly changed by ethanol feeding. Hepatic microsomal lipid peroxide value and the activities of glutathione(GSH) peroxidase and GSH reductase were not changed by either ethanol or 2-AAF treatment. However the analysis of cytochrome systems showed that both ethanol and 2-AAF increased cytochrome P-450 and bs contents although cytochrome P-450 content was moe affected by 2-AAF while cytochrome b5 content by ethanol. Cytosolic GSH S-transferase activity, which is often elevated during chemical carcinogenesis, also significantly increased by either ethanol feeding or 2-AAF treatment. Overall values for the cytochrome contents and GSH S-transferase activities were highest in 2-AAF treated rats fed ethanol. These results might support the hypothesis that the increase in liver cancer risk associated with chronic ethanol consumption might be due to, at least in part, enhancement of carcinogen bioactivation by ethanol.

• Journal of Nutrition and Health
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• v.25 no.2
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• pp.116-122
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• 1992

This study determined hepatic microsomal lipid peroxide values glucose 6-phosphatase NA-DPH-cytochrome P450 reductase and cytosolic glutathione S-transferase activites to examine the effects of methyl group deficiency on hepatic lipid peroxidation in rats treated with diethylni-trosamine(DEN) and 2-acetylamionfluorene(AAF) Weanling sprague Dawley male rats were fed the diet with methyl group supplemented or deficient. Two weeks after feeding rate were injected with a single of 200mg/kg body weight DEN intraperitoneally and after four weeks 0.02% AAF containing diets were fed for two weeks. Animals were sacrificed at 6th week. Microsomal lipid peroxide values were tended to increase in methyl group deficiency(MD). Especially in case of carcinogen tratments lipid peroxide values were increased significantly in MD. Microsomal glucose 6-phophatase activities were decreased by MD and carcinogens and in MD with carcinogen group (MD+C) the enzyme activites were the lowest Glucose 6-phosphatase activities were negatively correlated with lipid peroxidation. Microsomal NADPH-cytochrome P450 reductase activities were the highest in MD+C and correlated positively with lipid peroxidation. Cytosolic glutathione S-transferase activities were the highest in MD+C Methyl group deficiency induces lipid peroxidation especially in case of being exposed to carcinogens. Therefore the results suggest that lipid peroxidation may be one of the meachanisms of carcinogensis by methyl group deficiency.

• Journal of Food Hygiene and Safety
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• v.11 no.4
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• pp.291-297
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• 1996

The role of cytochrome P-450 2E1 (P450 2E1) in the early phase of alcoholic fatty liver was examined. Female rats were pretreated with either allyl sulfide (200 mg/kg, po), disulfiram (500 mg/kg, po), YH 439 (250 mg/kg, po) or pyrazine (200 mg/kg/day$\times$2 days, ip). Marked changes in carbon tetrachloride-induced hepatotoxicity and caboxyhemoglobin (COHb) elevation due to dichloromethane administration were observed in rats treated with one of the P450 2E1 modulators. A single dose of ethanol (6 g/kg, po) increased the hepatic triglyceride contents approximately 2 fold, which was inhibited completely by YH 439 pretreatment. However, the other P450 2E1 modulators failed to alter the ethanol-induced hepatic triglyceride accumulation. In vitro hepatic microsomal enzyme activity was determined in 4 week old premature and 12 week old adult rats. Aminopyrine-N demethylation was not different, but p-nitrophenol hydroxylation and p-nitroanisole O-demethylation were significantly higher in premature rats. However, no difference in the triglyceride accumulation induced by an intraperitoneal dose of ethanol (3 g/kg) was noted between premature and adult rats. The results suggest that the P450 2E1 activity dose not play an important role in the induction of acute alcoholic fatty liver.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.109-109
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• 2001

The present study was done to investigate the relationship between Kupffer cells and alteration of cytochrome P-450 (CYP)-dependent drug metabolizing enzyme activities during polymicrobial sepsis. Male rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP) followed by fluid resuscitation. The gadolinium chloride (GdC1$_3$, 10 mg/kg), blocker of Kupffer cells, was pretreated intravenously at 48 h and 24 h prior to the induction of CLP. All assay parameters were determined at 24 h after CLP or sham operation. In CLP-treated rats, the mortality rate of animals increased to 50% and serum alanine (ALT) and aspartate aminotransferase (AST) levels also significantly elevated. However, this increase was not suppressed by GdC1$_3$ pretreatment. Microsomal lipid peroxidation markedly increased after CLP operation. This increase was significantly attenuated by pretreatment. Total cytochrome P-450 content and NADPH-cytochrome P-450 reductase activity were not changed after CLP operation, but GdC1$_3$pretreatment reduced total cytochrome P-450 content, The hepatic microsomal CYP 1A1, 1A2, 2Bl and 2El activities in CLP-induced rats were also not significantly different from sham-operated rats. However, GdC1$_3$pretreatment showed a moderate increase in CYP1A1 and 1A2 activities. Our findings suggest that Kupffer cells may be partly responsible for producing hepatocellular dysfunction during sepsis.

• YAKHAK HOEJI
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• v.34 no.2
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• pp.69-79
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• 1990

The aim of this experiment is to observe the toxicity of cypermethrin[S, R- -cyano-3-phenoxybenzyl-(1R, 1s, cis, trans)-2,2-dimethyl-3-(2,2-dichlorovinyl) cyclopropane carboxylate]and to investigate the synergistic effect of piperonyl butoxide on the cypermethrin toxicity. In cypermethrin (CYP) treated group, the biochemical parameters such as ALT, LDH, glucose in serum were remarkably elevated. The content of cytochrome P-450 and activity of NADPH-cytochrome c reductase in renal microsomal fraction were increased but those in hepatic microsomal fraction were not significantly increased. The activity of aniline hydroxylase and ATPase in liver were decreased. In the case of CYP plus piperonyl butoxide (PB) treated group, AST, ALT, LDH and glucose were more increased. Cytochrome P-450 and NADPH-cytochrome c reductase in liver and kidney were supressed and aniline hydroxylase and ATPase in liver were more decreased. Especially, in the case of CYP plus PB 100 mg/kg treated group, hepatic TBA value was increased but activity of glucose-6-phosphatase was remarkably depressed.

• Toxicological Research
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• v.12 no.2
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• pp.265-270
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• 1996

Effects of a single administration of dichloromethane (DCM) on the hepatic drug metabollzing activity were determined using adult female rats. Rats were treated with DCM (3 mmol/kg, ip) and the disappearance of antipyrine (100 mg/kg, iv) or ethanol (2 g/kg, ip) from blood was measured. The blood concentration and half-life of antipyrine was not influenced by DCM administration. And DCM did not alter the blood concentration of ethanol measured for 240 min after the treatment. The effect of DCM treatment on in vitro cytochrome P-450-dependent enzyme activities was examined as well. No significant difference in either aniline hydroxylase or aminopyrine N-demethylase was observed in hepatic microsomal fractiorts of rats treated with DCM 24 hr prior to sacrifice. The present study indicates that acutely given DCM does not alter the metabolism of xenobiotics in vivo. The failure of DCM to alter the in vitro hepatic microsomal drug metabolizing activity was also noted.

• Journal of Nutrition and Health
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• v.25 no.1
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• pp.3-11
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• 1992

This paper examines the effects of dietary fats on the fatty acid composition and market enzyme activites during liver damage in 2-acetylaminofluorene treated rats. Weaning Sprague-Dawley male rats were fed the diet of beef tallow(BT source of sturated fatty acid) corn oil(CO source of n-6 fatty acid) and perilla oil(PO source of n-3 fatty acid) at the level of 15% fat. Ten days after feeding 2-acetylaminofluorene(2-AAF) was injected intraperitoneally twice every week at the level of 50mg/kg body weight for 7 weeks. Liver microsomal and cytosolic fractions were collected to determine the microsomal fatty acid composition lipid peroxide(malondialdehyde MDA) contents glucose 6-phosphatase(G6 Pase) activity cytochrome(Cyt) P-450 contents and cytosolic glutathione S-transferase(G6 Pase) activity cytochrome(Cyt) P-450 contents and cytosolic glutathione S-transferase(GST) activity. The fatty acid composition in microsomal fraction was reflected by different dietary fats. By 2-AAF treatment linoleic acids were increased regardless of the diet MDA contents were higher in CO group than it was in BT group. However 2-AAF treatment decreased MDA contents in all dietary groups. G6Pase activity of BT group was higher than those of the other gropus. CO group had the highest Cyt P-450 contents and 2-AAF treatment lowered Cyt P-450 contents only in CO gropu GST activites were higher in CO than in BT group whereas the enzyme activites were increased by 20AAF treatment in all dietary groups. These results suggest that dietary fats and 2-AAF treatment in all dietary groups,. These results suggest that dietary fats and 2-AAF treatment affect microsomal fatty acid composition The enzyme activities concerned with liver damage were influenced differently by dietary fats and 2-AFF treatment Although PO diet contains much more polyunsaturated fatty acids than CO diet PO diet doesn't cause more oxidant stress compared with CO diet in these data.

• Proceedings of the Ginseng society Conference
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• 1988.08a
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• pp.81-86
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• 1988

The effect of three polyacetylene compounds. panaxydol. panaxynol and panaxytriol isolated from Korean ginseng on $CCI_4-induced$ lipid peroxidation in vitro and in vivo hepatic microsomal lipid peroxidation were investigated. Lipid peroxide levels both in serum and liver and serum enzyme (GOT. GPT. LDH) activities of normal or $CCI_4-treated$ mice and rats were also determined after administration of polyacetylenes. Hepatic microsomal cytochrome P-450 content and activities of aniline hydroxylase and aminopyrine demethylase were measured after treatment of polyacetylenes with or without carbon tetrachloride. As results. treatment with polyacetylenes to control mice did not influence the levels of lipid peroxides and serum enzyme activities while panaxynol did. Panaxynol itself inhibited liver lipid peroxidation in normal mice. Polyacetylene compounds protected hepatic lipid peroxidation and lowered serum lipid peroxide levels induced by $CCI_4$ Polyacetylenes prevented leakage of LDH to serum but elevated GOT and GPT levels caused by $CCI_4$ were not changed by polyacetylene pretreatment. $CCI_4$ caused losses in the content of cytochrome P-450 and activities of aniline hydroxylase and aminopyrine demethylase. When polyacetylenes were treated without $CCI_4$ panaxydol and panaxynol induced aniline hydroxylase and all three polyacetylenes induced aminopyrine demethylase. Cytochrome P-450 contents were not affected by polyacetylenes. In vitro hepatic microsomal lipid peroxidation was inhibited by polyacetylenes and $DL-{\alpha}-tocopherol$ in a concentration-dependent manner.

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.4
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• pp.682-688
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• 1997

This study was performed to investigate whether ascorbic acid can modulate the induction of CYP2E1 and prevent the lipid peroxidation which may cause diabetic chronic complication. Diabetes was induced by intraperitoneal injection of streptozotocin to 5-week-old male Sprague-Dawley rats(150~170g). Normal and diabetic group was randomly divided into three groups each; Control(CON, no supplementation), SUP1 (50mg/d ascorbate supplementation) and SUP2(250mg/d ascorbate supplementation). Ascobic acid was prepared daily by dissolving in drinking water and supplied for 4 weeks. There was no difference in hepatic microsomal and mitochondrial P450 contents between normal and diabetes. Hepatic microsomal N-nitrosodimethylamine(NDMA) demethylase activity, which repre-sents contents of CYP2E1, was elevated in diabetes, but not significantly. The NDMA demethylase activity of diabetic SUP2 group was significantly lower activity than that of the diabetic CON group. However, no difference in hepatic mitochondrial NDMA demethylase activity was observed between the diabetes and the normal group. The result suggests that the induction of CYP2E1 in diabetes can be alleviated by ascorbic acid supplementation at the dose of 50mg1d. In addition, ascorbic acid supplementation showed dose-dependent reduction of hepatic microsomal TBARS contents in diabetic rats.