• Journal of Life Science
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• v.8 no.6
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• pp.695-701
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• 1998

This study was carried out to investigate levels of the components of microsomal mixed function oxidase (MFO) system and activities of the hepatic microsomal cytochrome P45O (P45O)-dependent monooxygenases of grass snake (Natrix tigrina Lateralis) and to compare with those of rat. The levels of P45O and cytochrome b$_{5}$, (b$_{5}$) of snake were much lower than those in rat. NADPH-cytochrome c reductase activity in the snake was also only 40% of that in the rat. Activities of 7-ethoxycoumarin 0-deethylase (ECOD) and benzphetamine N-demethylase (BPDM) of snake hepatic microsomes, when compared with those of rat, were markedly low. But, aryl hydrocarbon hydroxylase (AHH) and testosterone hydroxylase (TSH) activities were nearly the same or higher than those of the rat. Of the P45O-dependent TSHs measured, 7$\alpha$-hydroxylase activity was the highest in snake, whereas, 6$\beta$-hydroxylase activity was the highest in rat. However, stereoselectivity of the enzyme from the snake to C2 and C6 positions of testoste-rone was the same as rat. The result of radioimmunoassay (RIA) for the identification of five P45O isozymes with MAbs shows that relatively high content of ethanol-inducible P45O isozyme, CYP2El, exists in the rat, whereas MC-inducible P45O isozyme, CYP2A1/1A2, does in the snake. From the analyses of SDS-PAGE and RIA of partially pu-rified P45O, we suggest the possibility of the presence of a certain P45O isozyme(s) in hepatic microsomes of snake different from those of rat.

• Environmental Analysis Health and Toxicology
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• v.7 no.3_4
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• pp.57-67
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• 1992

BPMC (2-Sec-butylphenyl N-methylcarbamate) was treated at the level of 100mg/kg/day in oral administration for 12th days in rat. It was investigated not only that the hematogram and the serological parameters, but also the content of cytochrome P-450, the activity of TBA, glucose-6-phosphatase, cholinesterase and carboxylesterase in rat. The results were as follows: The hematogram was not found any alteration but the value of AST, ALT, LDH and the content of glucose in serum were significantly increased compare with that of control group. The content of cytochrome P-450 in liver was increased significantly on the contrary cytochrome P-450 in kideny and NADPH-cytochrome c reductase in liver and Kidney were not significantly increased. After the final 12th day, the value of TBA and the activity of glucose-6-phosphatase appeared to the tendency of increasement in the liver. The activity of cholinesterase and carboxylesterase both in serum and liver were decreased. Especially the activity of cholinesterase was more significantly decreased. It was conclusion that the function of this insectivide should be due th the inhibition of cholinesterase activity.

• Environmental Analysis Health and Toxicology
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• v.7 no.3_4
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• pp.17-35
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• 1992

In this study, it was examined the toxic effects of combination of buprofezin and carbaryl on hematological, biological and enzymetic parameters in rats. The administration of buprofezin or carbaryl both induced the tissue content of cytochrome P-450 and furthermore, the combination of the both increased significantly the liver content of cytochrome P-450 in rat. But cytochrome P-450 and NADPH -cytochrome c reductase activities in kidney were slightly increased. Administration of carbaryl and combination of the both also significantly increased hepatic aniline hydroxylase activity. In addition, in the combination group, glucose-6-phosphatase and lipid peroxidase activities were changed in the rat liver. Furthermore, cholinesterase was inhibited in rats treated with carbaryl or the combination of buprofezin and carbaryl. The above results suggested that the combined administration of buprofezin and carbaryl can induce more toxic effects than the single administration of buprofezin or carbaryl.

• The Korean Journal of Pharmacology
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• v.21 no.1
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• pp.1-11
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• 1985

The effects of feeding indole, indole-3-carbinol and benzofuran (all at 5 mmole/kg body wt./day) on various hepatic microsomal and cytosolic enzyme activities involved in xenobiotic metabolism have been compared. Benzofuran was found to elevate the activities of many enzymes both in microsomes (e.g., aniline hydroxylase, 7-ethoxycoumarin O-deethylase, p-nitrophenol UDPGA-transferase and epoxide hydrolase) and in cytosol (e.g., glutathione reductase, glutathione S-transferase, NADH:quinone reductase and UDP-glucose dehydrogenase). The structures of indole and indole-3-carbinol are similar to benzofuran except for the substitution of nitrogen with oxygen atom within the furan ring. Results showed that the activities of UDPGA-transferase and NADH:quinone reductase were not elevated by these indole compounds. While the chemical structure of these two indole compounds are identical except for the presence of the carbinol (methanol) group in indole-3-carbinol, there were marked differences in the types and activities of microsomal enzymes that were enhanced. Among the microsomal enzyme activities determined, indole elevated only the NADPH:cytochrome c reductase, while indole-3-carbinol increased several mixed function oxidase and particularly the epoxide hydrolase activities. Based on the chemical structures of tested compounds and the observed results, possible explanations for the mechanisms involved in elevating epoxide hydrolase activity by benzofuran and indole-3-carbinol are discussed.

• 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.

• Toxicological Research
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• v.13 no.3
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• pp.183-186
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• 1997

Acute toxicity of pectenotoxin 2 (PTX2) was examined in mice. Treatment of mice with a toxic dose of PTX2 resulted in clinical signs such as ataxia, cyanosis and an abrupt decrease in body temperature. Histopathological studies revealed that the liver is the major target organ for PTX2. Activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and sorbitol dehydrogenase (SDH) were significantly elevated by PTX2 administration. Glucose-6-phosphatase activities were not changed by the treatment. The PTX2 treatment decreased relative liver weight without changing the body weight. The effect of PTX2 on hepatic drug metabolizing enzyme system was determined. An ip dose of PTX2 (200 $\mu$g/kg) induced a significant decrease in the hepatic microsomal protein content. Cytochrome P-450 content, cytochrome b$_5$ content, NADPH cytochrome c reductase, aminopyrine N-demethylase activities, or hepatic glutathione content were not altered by PTX2 treatment.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.188-188
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• 2001

Human cytochrome B5 (CYB5) was coexpressed with cytochrome P450 1A2 (CYP1A2), NADPH-CYP450 reductase (CYPR) and Ν-acetyltransferase 2 (NAT2) in Chinese hamster ovary (CHO) cells. The expression of four proteins was determined by Western blot analyses. The introduction of cDNAs to CHO cells were transduced via retroviral vectors. The cytotoxicity assay of 2-aminoanthracene (2-AA) and aflatoxin B$_1$were approximately 4-fold more sensitive than CYB5 free cells.(omitted)

• Toxicological Research
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• v.4 no.1
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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.

• YAKHAK HOEJI
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• v.23 no.2
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• pp.111-118
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• 1979

It was previously reported that cytochrome P$_{450}$ content in liver was increased when Capsicum acetone extract was given chronically to rats. The present study is aimed to investigate the effect of capsaicin, a principal component of red pepper, on the drug metabolizing enzymes in rat liver. Capsaicin (5mg/kg) was given intraperitoneally once a day for seven days and zoxazolamine paralysis time and hexobarbital sleeping time were determined 24 hrs after the last dose of capsaicin. Plasma hexobarbital concentration was also determined five and 15 min after hexobarbital administration to rats. Zoxazolamine paralysis time and hexobarbital sleeping time were shortened by 31.6% and 37.1%, respectively, compared with control group. Plasma hexobarbital concentration was lowered by 26.2% after five min and by 35.2% after 15 min, respectively, compared with control group. However, administration of single dose of capsaicin did not affect the zoxazolamine paralysis time and hexobarbital sleeping time. Microsomal cytochrome P$_{450}$ content and NADPH-cytochrome C reductase activity were increased by 14.6% and 11.6%, respectively in the rats pretreated with capsaicin for seven days, while cytochrome b$_{5}$ content was not changed. These results suggest that treatment with capsaicin for seven days may induce the drug metabolizing enzyme in rat liver.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.579-585
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• 2003

The studies were carried out on the correlation between microsomal lipid peroxidation level and drug metabolizing enzyme activities in rat liver microsomal suspensions on various ages (2-week-old, 2, 4, 8, and 12-month-old). The lipid peroxidation levels of liver homogenates tended to be elevated in a 4-month-old rat livers, but it was a little decreased in 8 and 12-month-old rat livers. The lipid peroxidation levels of microsomal suspension was not shown any significant differences by ages. Lipid peroxidation levels and microsomal cytochrome P450 and NADPH-cytochrome c reductase activity showed a direct correlation (r=0.72 and r=0.64), respectively. The activities of cytochrome P450-dependent aminopyrine-N-demethylase and benzpyrene hydroxylase in rat liver microsomes were increased by ages up to 8-month-old rats and maintained in 12-month-old rats. The correlation between lipid peroxidation levels and these cytochrome-dependent enzyme activities showed a high direct correlation (r=0.97 and r=0.81), respectively.