• Environmental Analysis Health and Toxicology
• /
• v.3 no.3_4
• /
• pp.39-51
• /
• 1988

Effects of ${\alpha}$-tocopherol and perilla oil on the toxicity of polychlorinated biphenyls (PCB) in male rat were studied. Rats were fed ad libitum for 6 weeks with the animal diet which contains PCB 30 ppm and 100 ppm. Perilla oil (0.5 g/kg body weight) and ${\alpha}$-tocopherol (30 mg/kg body weight) were administered intraperitoneally twice a week for 6 weeks. Rats fed with PCB showed enlargement of liver and spleen, increase in aspartate aminotransferase, alkaline phosphatase, sereum lipid and cytochrome P 450 and decrease in body weight and glutathione. When perilla oil was administered to rats fed with PCB increase in aspartate aminotransferase, alkaline phosphatase, serum lipid and cytochrome P45O and decrease in body weight and glutathione were significantly augmented, compared to rats fed with PCB alone. This means that perilla oil potentiates the toxicity of PCB. On the other hand when ${\alpha}$-tocopherol was administered to rats fed with PCB increase in aspartate aminotransferase, alkaline phosphatase, serum lipid and cytochrome P45O and decrease in body weight and glutathione were signigicantly reduced, compared to rats fed with PCB alone. This means that u-tocopherol reduces the toxicity of PCB. From the above results, it may be concluded that PCB is metabolized by microsomal mixed function oxidase and the metabolite causes the toxicity and microsomal glutathione plays a role of protection on the toxicity of PCB.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.22 no.4
• /
• pp.373-382
• /
• 2000

Individual genetic susceptibilities to cancers may result from several factors including differences in xenobiotics metabolism to chemical carcinogens, DNA repair, altered oncogenes and suppressor genes, and environmental carcinogen exposures. Among them, genetic polymorphisms of metabolizing enzymes to chemical carcinogens have been recognized as a major important host factors in human cancers. They have two main types of enzymes: the phase I cytochrome P-450 mediating enzymes (CYPs) and phase II conjugating enzymes. The purpose of this study is to determine the frequencies of genotypes of phase I (CYP1A1 and CYP2E1) and phase II (NAT2) metabolizing enzymes in healthy control and head and neck cancer patients of Korean and to identify the relative high risk genotypes of these metabolizing enzymes to head and neck cancer in Korean. The author has analyzed 132 head and neck cancer patients and 113 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results were as following; 1. The frequencies of genotypes of CYP1A1, CYP2E1 and NAT2 in healthy control were as following; CYP1A1 exon 7 polymorphism; Ile/Ile: Ile/Val: Val/Val = 59.3%: 36.3%: 4.4% CYP2E1 Pst I polymorphism, C1/C1: C1/C2: C2/C2 = 61.1%: 32.1%: 6.2% NAT2 polymorphism; F/F: F/S: S/S = 43.4%: 48.7%: 8.0% 2. In analysis of phase I enzyme, Val/Val genotype in CYP1A1 exon 7 polymorphism and C2/C2 genotype in CYP2E1 Pst I polymorphism were associated with relative high risks to head and neck cancers (Odds' ratio: 2.09 and 1.37, respectively). 3. Among the genotypes of NAT2 enzyme polymorphism, S/S genotype of NAT2 enzyme had 1.03 times of relative risk to head and neck cancers. 4. In combined genotyping of CYP1A1, CYP2E1, and NAT2 enzymes polymorphisms, the patients with Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator had higher relative risks than the patients with each baseline of combined genotypes (Odds' ratio: 2.82, 1.98 and 2.1, respectively). These results suggest the combined genotypes of Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator were more susceptible to head and neck cancers in Korean. And genotyping of metabolizing enzymes could be useful for predicting individual susceptibility to head and neck cancer.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.23 no.4
• /
• pp.561-567
• /
• 1994

This study was designed to evaluate the effects of dietary vitamin E and caffeine on the activities of lipid peroxidation related enzymes in rat liver . Male Sprague-Dawley rats were fed on diets containing three level of vitamin E (37.5, 750 or 1,5oomg/kg diet) and with or without 0.3% caffeine. The rats were sacrificed after 5 and 10 weeks of feeding. Results obtained from this study were as follows ; The content of cytochrome P450 tended to increase as dietary vitamin E level was raised. The activity of xanthine oxidase increased in the caffeine groups, but it decreased by the increasing level of vitamin E. Superoxide dismutase and catalase activity were slightly elevated by dietary supplementation of vitamin E. And there was a tendency of higher these enzyme activity of caffeine groups. The activity of glutathione perxidase tended to decrease as dietary vitamin E level increased. But it was raised by caffeine supplementation . Liver glutathione content was not affected by dietary supplementation of vitamin E, but it showed a decreasing tendency in caffeine groups. There was a tendency of more lipid peroxide content of caffeine groups than that of the only vitamin E supplemented group. But the degree of increment of this decreased as dietary vitamin E level increased.

• Journal of Oriental Neuropsychiatry
• /
• v.8 no.2
• /
• pp.51-62
• /
• 1997

This experiment was done to investigate the antioxidant effect of Ondamtang(ODT) on brain tissues of rats. The experimental groups were divided into three groups and treated as follows for a fifteen days ; Negative control group(NC), Vitamin E admistrated group(PC), ODT administrated Group(ODT). After the extracting microsome from brain of rats, those were measured the amounts of Malondiadehyde and Hydrogen peroxide, then activities of antioxidant enzymes like Superoxide dismutase, Catalase and NADPH-cytochrome P-450 reductadse. The results were as follows; 1. In TBA reaction to measure the amount of MDA, oxidant material of brain tissue of rats, the group treated by ODT showed significant decrease. 2. In the formation of Hydrogen peroxide, the group treated by ODT showed no change in comparison with normal group. 3. The activity of SOD in the group treated by ODT showed a little increase in comparison with normal group. 4. The activity of Catalase was increased significantly in the group treated by ODT than normal group. 5. The activity of NADPH-cytochrome P-450 reductase in the group treated by ODT showed a little increase in comparison with normal group. According to the above results, it is suggested that Ondamtang(ODT) has some antioxidant effects on tissues of brain.

• Biomolecules & Therapeutics
• /
• v.21 no.6
• /
• pp.487-492
• /
• 2013

Cytochrome P450 4A11 (CYP4A11) is a fatty acid hydroxylase enzyme expressed in human liver. It catalyzes not only the hydroxylation of saturated and unsaturated fatty acids, but the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a regulator of blood pressure. In this study, we performed a directed evolution analysis of CYP4A11 using the luminogenic assay system. A random mutant library of CYP4A11, in which mutations were made throughout the entire coding region, was screened with luciferase activity to detect the demethylation of luciferin-4A (2-[6-methoxyquinolin-2-yl]-4,5-dihydrothiazole-4-carboxylic acid) of CYP4A11 mutants in Escherichia coli. Consecutive rounds of random mutagenesis and screening yielded three improved CYP4A11 mutants, CP2600 (A24T/T263A), CP2601 (T263A), and CP2616 (A24T/T263A/V430E) with ~3-fold increase in whole cells and >10-fold increase in purified proteins on the luminescence assay. However, the steady state kinetic analysis for lauric acid hydroxylation showed the significant reductions in enzymatic activities in all three mutants. A mutant, CP2600, showed a 51% decrease in catalytic efficiency ($k_{cat}/K_m$) for lauric acid hydroxylation mainly due to an increase in $K_m$. CP2601 and CP2616 showed much greater reductions (>75%) in the catalytic efficiency due to both a decrease in $k_{cat}$ and an increase in Km. These decreased catalytic activities of CP2601 and CP2616 can be partially attributed to the changes in substrate affinities. These results suggest that the enzymatic activities of CYP4A11 mutants selected from directed evolution using a luminogenic P450 substrate may not demonstrate a direct correlation with the hydroxylation activities of lauric acid.

• Journal of Oriental Neuropsychiatry
• /
• v.9 no.1
• /
• pp.45-57
• /
• 1998

The effect of HWANSODAN(HSD), on the level of brain antioxidants was examined in aged rat. The experimental groups were divided into three groups and treated as follows ; normal group(negative control), Vt.E administrated Group(HSD). The purified microsome from brain tissue, those were measired the amounts of oxidant materials like Malonfialdehyde(MDA) and H2O2, then activities of antioxidants enzymes like superoxide dismutase, catalase, NADPH-cytochrome P-450 reductase.The results were as follows;1. In TBA reaction to measure the amount of MDA, HSD group and Vt.E group did not showed signigicant decrease.2. In the formation of Hydrogen peroxide, HSD group and Vt.E group showed a little increase.3. The activity of Superoxide dismutase was increased significantly in HSD group and Vt.E group.4. In the activity of Catalase, Vt.E group was increased significantly and HSD group a little increased. 5. The activity of NADPH-cytochrome P-450 reductase in the HSD group and Vt.E group showed significantly increase.According to the above results, it is suggested that HWANSODAN(HSD) has some antioxidant effects on the tissue of brain.

• Journal of Oriental Neuropsychiatry
• /
• v.9 no.1
• /
• pp.59-71
• /
• 1998

The effect of Samyonjihwangtang(SJT) on th level of brain antioxidants was examined in aged rat. Samyongjihwangtang(SJT) is assed Cervi Pantiri-chum Cornu, Ginseng Radix to Yukmijihwangtang. The experimental groups were divided into three groups and treated as follows ; normal group(NC), Vt.E administrated group(PC), SJT administrated Group(SJT). From the purified microsome of brain tissue, those were measures the amounts of oxidant materials like malonaldehyde(MDA) and H_2O_2, then activities of antioxidants enxymes like Superoxide dismutase, Catalase, NADPH-cytochrome P-450 reductase.The results were as follows;1. In TBA reaction to measure the amount of MDA, oxidant material of brain tissue of aged rat, both treated groups showed significant decrease.2. In the formation of Hydrogen peroxide, the treated group(SJT) showed a little decrease.3. The activity of Superoxide dismutase was increased significantly in both treated groups than normal group.4. the activity of Catalase was increased significantly in both treated groups than normal group. 5. The activity of NADPH-cytochrome P-450 reductase in the treated group(SJT) showed a little increase.According to the above results, it is suggested that Samyongjihwangtag(SJT) has some antioxidant effects on the tissue of brain.

• Development and Reproduction
• /
• v.25 no.1
• /
• pp.15-24
• /
• 2021

Benzo[a]pyrene (B[a]P) is a potent carcinogen and is classified as an endocrine-disrupting chemical. In mammalian testes, Sertoli cells support spermatogenesis. Therefore, if these cells are negatively affected by exposure to xenotoxic chemicals, spermatogenesis can be seriously disrupted. In this context, we evaluated whether mouse testicular TM4 Sertoli cells are susceptible to the induction of cytotoxicity-mediated cell death after exposure to B[a] P in vitro. In the present study, while B[a]P and B[a]P-7,8-diol were not able to induce cell death, exposure to BPDE resulted in cell death. BPDE-induced cell death is accompanied by the activation of caspase-3 and caspase-7. Depolarization of the mitochondrial membrane and cytochrome c release from mitochondria were observed in benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-treated cells. These results indicate that TM4 cells are susceptible to apoptosis in a caspase-dependent manner. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that aryl hydrocarbon receptor (AhR) expression was almost undetectable in TM4 cells and that its expression was not altered after B[a]P treatment. This indicates that TM4 cells are nearly AhR-deficient. In TM4 cells, the CYP1A1 protein and its activity were not present. From these results, it is clear that AhR may be a prerequisite for CYP1A1 expression in TM4 cells. Therefore, TM4 cells can be referred to as CYP1A1-deficient cells. Thus, TM4 Sertoli cells are believed to have a rigid and protective cellular machinery against genotoxic agents. In conclusion, it is suggested that tolerance to B[a]P cytotoxicity is associated with insufficient AhR and CYP1A1 expression in testicular Sertoli cells.

• Archives of Pharmacal Research
• /
• v.28 no.10
• /
• pp.1196-1202
• /
• 2005

Omeprazole (OMP) is a proton pump inhibitor used as an oral treatment for acid-related gastrointestinal disorders. In the liver, it is primarily metabolized by cytochrome P-450 (CYP450) isoenzymes such as CYP2C19 and CYP3A4. 5-Hyroxyomeprazole (5-OHOMP) and omeprazole sulfone (OMP-SFN) are the two major metabolites of OMP in human. Cimetidine (CMT) inhibits the breakdown of drugs metabolized by CYP450 and reduces, the clearance of coad-ministered drug resulted from both the CMT binding to CYP450 and the decreased hepatic blood flow due to CMT. Phenobarbital (PB) induces drug metabolism in laboratory animals and human. PB induction mainly involves mammalian CYP forms in gene families 2B and 3A. PB has been widely used as a prototype inducer for biochemical investigations of drug metabolism and the enzymes catalyzing this metabolism, as well as for genetic, pharmacological, and toxicological investigations. In order to investigate the influence of CMT and PB on the metabolite kinetics of OMP, we intravenously administered OMP (30 mg/kg) to rats intraperitoneally pretreated with normal saline (5 mL/kg), CMT (100 mg/kg) or PB (75 mg/kg) once a day for four days, and compared the pharmacokinetic parameters of OMP. The systemic clearance ($CL_{t}$) of OMP was significantly (p<0.05) decreased in CMT-pretreated rats and significantly (p<0.05) increased in PB-pretreated rats. These results indicate that CMT inhibits the OMP metabolism due to both decreased hepatic blood flow and inhibited enzyme activity of CYP2C19 and 3A4 and that PB increases the OMP metabolism due to stimulation of the liver blood flow and/or bile flow, due not to induction of the enzyme activity of CYP3A4.

• Journal of Preventive Medicine and Public Health
• /
• v.28 no.1 s.49
• /
• pp.141-152
• /
• 1995

This study was performed to find out the influences of ethanol on the metabolism of trichloroethylene(TRI) in rats. TRI in corn oil at the dosage of 150, 300, 600 mg/kg was injected peritoneally once a day for two days to two groups. In one group ethanol(4 g/kg) was taken orally 30 minutes before TRI injection, and the other group ethanol was not. The results of experiments are as follows: 1. The contents of cytochrome P-450 and $b_5$ had inverse relationship with in-jected TRI amounts in both groups. 2. The activity of NADPH P-450 reductase was decreased slowly in TRI injected group related with TRI amount, but decreased drastically in the group pretreated with ethanol. 3. The activity of NADH $b_5$ reductase had relationship with injected nt amount , but the statistical significance was found only in the groups of 300 and 600 mg/kg of TRI injected without relevance to ethanol when compared with the group that was not injected. 4. The activity of ADH was more decreased and ALDH activity was more increased in groups that TRI injected and ethanol was pretreated with ethanol groups than in group without any treatment. These results suggest that ethanol may inhibit epoxide formulation, the first step of TRI metabolism, and change from TCE-OH to TCA also.