• Title/Summary/Keyword: cytochrome $b_5$

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Toxicity and Changes in Hepatic Metabolizing Enzyme System Induced by Repeated Administration of Pectenotoxin 2 Isolated from Marine Sponges (해면체에서 추출한 Pectenotoxin 2의 마우스에서의 반복적인 투여에 의한 독성 및 간대사효소계에 주는 영향)

  • Yoon, Mi-Young;Kim, Young-Chul
    • Korean Journal of Pharmacognosy
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    • v.28 no.4
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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.

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Identification of Deer Antler Species Using Sequence Analysis and PCR-RFLP of Mitochondrial DNA (사슴 미토콘드리아 DNA의 염기서열 및 PCR-RFLP분석에 의한 녹용의 종 감별)

  • Shin, Ki-Hyun;Shin, Sung-Chul;Chung, Ku-Young;Chung, Eui-Ryong
    • Food Science of Animal Resources
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    • v.28 no.3
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    • pp.276-282
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    • 2008
  • It is estimated that over 80% of deer antlers produced in the world are consumed in Korea. However, mislabeling or fraudulent replacement of costly antlers with cheaper ones is one of the most common problems in the domestic antler market. Therefore, there is a great need for the development of technology to identify species of antlers. This study was carried out to develop an accurate and reliable method for the identification and authentication of species or subspecies of antlers using DNA sequence analysis and comparison of mitochondrial cytochrome band D-loop region genes among antlers of five deer species, Cervus elaphus sibericus, Cervus elaphus canadensis, Cervus nippon, Cervus elaphus bactrianus and Rangifer tarandus. A variable region of cytochrome band D-loop genes was amplified using PCR with specifically designed primers and sequenced directly. The cytochrome band D-loop region genes showed different DNA sequences between the species of antlers and thus it is possible to differentiate between species on the basis of sequence variation. To distinguish between reindeer (Rangifer tarandus) antlers and other deer antlers, PCR amplicons of the cytochrome b gene were digested with the restriction enzymes NlaIV and TaqI, respectively, which generates a species-specific DNA profile of the reindeer. In addition, samples of 32 sliced antlers labeled Cervus elaphus sibericus from commercial markets were collected randomly and the mt DNA D-loop region of these antler samples was sequenced. Among the antler samples investigated, only 62.5% were from Cervus elaphus sibericus, and others were from Cervus elaphus bactrianus (25.0%), elk (Cervus elaphus canadensis) and reindeer (Rangifer tarandus). Our results suggest that DNA sequencing of mt DNA and PCR-RFLP methods using NlaIV and TaqI enzymes are useful for the identification and discrimination of deer antler species by routine analysis.

The Anti-hepatotoxic Effect of Ginseng in Rats: Meta-analysis

  • Kook, Se-Jeong;Han, Hye-Kyoung;Kim, Gun-Hee;Choi, Ki-Heon
    • Journal of the Korean Data and Information Science Society
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    • v.19 no.3
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    • pp.937-949
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    • 2008
  • The purpose of this meta-analysis was to investigate the anti-hepatotoxic effect of ginseng in rats induced with CC14 or TCDD, the toxicities that cause liver damages. Primary studies were collected from the ScienceDirect database, the DBpia, and the KISS. The data on the effect factors in plasma and in enzyme are listed as many as possible: The effect factors were alanine transaminase(ALT), aspartate transaminase(AST), liver aminopyrine N-demethylase(AD), liver aniline hydroxylase(AH), liver 3,4-Methylenedioxyamphetamine(liver MDA), cytochrome P450(P450), serum alkaline phosphatase(ALP), serum lactate dehydrogenase(LDH), cytochrome b5(Cyto b5), glutathione reductase (GR), Liver glutathione S-transferase(GST), liver glutamyltransferase (GT), Liver($\gamma$-GCS), serum liver 3,4-Methylenedioxyamphetamine(serum MDA), serum sorbitol dehydrogenase(SDH), serum total protein(TP), and serum $\gamma$-glutamyltransferase($\gamma$-GT). In order to investigate the effect of ginseng, the standard mean difference(HG) between the group of rats induced with toxicity(RH) and the group of rats induced with ginseng(RHG) were combined, and the significance of HGs were tested. The combined HGs checked the biases caused by heterogeneity among studies and the publication biases. Then they were adjusted by using the random effect model and trim and fill method. Although the publication biases were assumed, among all plasma factors the HGs of ALT, AST, serum MDA, SDH, TP, and $\gamma$-GT were significant, and among all enzyme factors the HGs of liver MDA, Cyto b5, GR, GST, and GT were significant. The treatment with ginseng significantly affected the plasma and enzyme levels in rats induced with toxicity.

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The Anti-hepatotoxic Effect of Ginseng in Rats: Meta-analysis

  • Kook, Se-Jeong;Han, Hye-Kyoung;Kim, Gun-Hee;Choi, Ki-Heon
    • Journal of Ginseng Research
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    • v.32 no.2
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    • pp.161-170
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    • 2008
  • The aim of this meta-analysis was to systematically investigate the anti-hepatotoxic effect of ginseng in rats induced toxicity which damage to liver. Primary researches were gained on the ScienceDirect database, the DBpia, and the KISS, and the data about the effect factors in plasma and in enzyme were listed as many as possible. The effect factors were alanine transaminase (ALT), aspartate transaminase (AST), liver aminopyrine N-demethylase (AD), liver aniline hydroxylase (AH), liver 3,4-Methylenedioxyamphetamine (liver MDA), cytochrome P450 (P450), serum alkaline phosphatase (ALP), serum lactate dehydrogenase (LDH), cytochrome b5 (Cyto b5), glutathione reductase (GR), Liver glutathione S-transferase (GST), liver glutamyltransferase (GT), Liver (${\gamma}-GCS$), serum liver 3,4-Methylenedioxyamphetamine (serum MDA), serum sorbitol dehydrogenase (SDH), serum total protein (TP), serum ${\gamma}-glutamyltransferase$ (${\gamma}-GT$). To investigate the effect of ginseng, the mean difference (MD) between the group of rats induced by toxicity (RH) and the group of rats induced by toxicity with ginseng (RHG) were combined, and the significance of MDs were tested. The combined MDs were checked the biases caused by heterogeneity among studies and the publication biases, and adjusted by using random effect model and trim and fill method, respectively. The effect about ALT, AST, ALP, LDH, SDH, TP and ${\gamma}-GT$ in plasma factors were significant, and about AD, liver MDA, P450, Cyto b5, GR, GST, GT and ${\gamma}-GCS$ in enzyme factors were significant. The treatment with ginseng supplementation was significantly effected on plasma and enzyme factors of damaged-rats.

Expression of cytochrome P-450(CYP)2B1/2 in lymphocytes of workers exposed to toluene and xylene (Toluene과 Xylene 노출 근로자의 림포사이트에서 Cytochrome P-450(CYP)2B1/2의 발현)

  • Kim, Ki-Woong
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.21 no.1
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    • pp.49-54
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    • 2011
  • In order to develop the methods for exposure assessment and find susceptibility markers for the workers who are exposed to low doses of toluene, xylene and other chemical in petroleum industries, we investigated the application of P-450 expression in human lymphocytes utilizing mouse monoclonal anti-rat CYP2B1/2, the levels of toluene and xylene in air and their metabolite levels in urine with the levels of expressed CYP2B1/2 proteins. The general characteristics such as age, smoking and drinking habit were no significant difference between the control and exposed workers, but the working durations and working hours were significantly different. Workers in exposed group were exposed to the mean of 2.1 ppm (range, 0.00-4.54) of toluene and 0.3 ppm (rang, 0.00-1.23) of xylene. The mean concentration of urinary hippuric acid was low and less than 1/5 of the biological exposure index recommended by the Ministry of Employment and Labor Korea. Methyl hippuric acid in urine was not detected in control and exposed workers. Also, there were no significant differences in the levels of the urinary metabolites between the control and exposed group. When chemiluminescence dot blottings were carried out utilizing mouse monoclonal antibody against CYP2B1/2, the strong density dots corresponding to a mouse monoclonal antibody was observed in the human lymphocytes from the exposed workers. These results suggested that the chemiluminescence dot blot assay for CYP of lymphocytes should be valuable for identifying CYP expression as biomarkers in the workers exposed to toluene and xylene.

Protective Effects of Chlorella vulgaris Extract on Carbon Tetrachloride-induced Acute Liver Injury in Mice

  • Kim, Hyun-Kyung;Li, Li;Lee, Hyeong-Seon;Park, Mi-Ok;Bileha, Dinesh;Li, Wei;Kim, Yong-Ho
    • Food Science and Biotechnology
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    • v.18 no.5
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    • pp.1186-1192
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    • 2009
  • The purpose of this study was to evaluate the protective effects of Chlorella vulgaris extract (CVE) against carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in mice. The mice received silymarin (100 mg/kg), intragastrieally (i.g.) and CVE (50, 100, and 200 mg/kg, i.g.), respectively, every other day, for 4 weeks before $CCl_4$ administration. Twenty-four hr after the administration of $CCl_4$, the serum and liver were analyzed. Our study found that in the CVE groups, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels had decreased significantly and the tissue injury was notably diminished compared to the $CCl_4$ group. The antioxidant activities of CVE groups, such as superoxide dismutase (SOD), catalase, and glutathione (GSH), were significantly increased and the activity of nitric oxide synthase (NOS) was remarkably increased in a CVE concentration-dependent manner. In the CVE groups, cytochrome P450 2B1/2B2 (CYP2B1/2) content was decreased. These results indicate that CVE has protective effects against $CCl_4$-induced hepatotoxicity via stimulation of the antioxidant activity and nitric oxide (NO) production, and through inhibition of CYP2B1/2.

Genetic Diversity of Thread-sail Filefish Stephanolepis cirrhifer Populations in Korean Coastal Waters Inferred from Mitochondrial DNA Sequence Analysis

  • Yoon, Moon-Geun;Jung, Ju-Yeon;Nam, Yoon-Kwon;Kim, Dong-Soo
    • Fisheries and Aquatic Sciences
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    • v.14 no.1
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    • pp.16-21
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    • 2011
  • The genetic diversity and population genetic structure of thread-sail filefish, Stephanolepis cirrhifer (Temminck & Schlegel), were examined with a nucleotide sequence analysis of a 495bp fragment of the 5'-end of the cytochrome b gene in 113 fish collected from five populations from the south and east coasts of the Korean Peninsula. Seventeen variable nucleotide sites and 16 haplotypes were defined. The observed haplotypes had a shallow haplotype genealogy and no geographical association. Most of the populations had high haplotype diversity and low nucleotide diversity, and significant negative values for Fu's $F_S$, suggesting rapid, recent population growth from an ancestral population and sudden population expansion. The estimated pairwise fixation indices ($F_{ST}$) indicate that substantial gene flow occurs among these populations. Thread-sail filefish in the South Sea of Korea and East Sea Korean populations forms a single panmictic population. Thus, thread-sail filefish in these areas should be treated as one management unit.

The Beneficial Effect of Trolox on Sepsis-Induced Hepatic Drug Metabolizing Dysfunction

  • Park, Sang-Won;Lee, Sun-Mee
    • Archives of Pharmacal Research
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    • v.27 no.2
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    • pp.232-238
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    • 2004
  • Trolox is a hydrophilic analogue of vitamin E. The aim of this study was to investigate its effects on hepatic injury, especially alteration in cytochrome P450 (CYP)-dependent drug metabolism during polymicrobial sepsis. Rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). The rats were treated intravenously with Trolox (2.5 mg/kg) or vehicle, immediately after CLP. Serum aminotransferases and lipid peroxidation levels were markedly increased 24 h after CLP. This increase was attenuated by Trolox. Total CYP content and NADPH-P450 reductase activity decreased significantly 24 h after CLP. This decrease in CYP content was attenuated by Trolox. At 24 h after CLP, there was a significant decrease in the activity of these CYP isozymes: CYP1A1, 1A2, 2B1, and 2E1. However, Trolox differentially inhibited the decrease in CYP isozyme activity. Trolox had little effect on the decrease in CYP1A1 activity but Trolox significantly attenuated decreases in CYP1A2 and 2E1 activities. In fact, Trolox restored CYP2B1 activity to the level of activity found in control rats. Our findings suggest that Trolox reduces hepatocellular damage as indicated by abnormalities in hepatic drug-metabolizing function during sepsis. Our data also indicates that this protection is, in part, caused by decreased lipid peroxidation.

Effects of Vitamin E on the Microsomal Mixed Function Oxidase System of Kidney in Streptozotocin-induced Diabetic Rats (식이 Vitamin E가 Streptozotocin 유발 당뇨쥐 신장조직에서의 Microsomal Mixed Function Oxidase System에 미치는 영향)

  • 신주영
    • Journal of Nutrition and Health
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    • v.33 no.6
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    • pp.619-624
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    • 2000
  • The purpose of this study was to investigate the effects of vitamin E on microsomal mixed function oxidase system of kidney in streptozotocin(STZ) induced diabetic rats. Sprague-Dawley male rats weighing 140$\pm$10g were randomly assigned to one control and three STZ-diabetic groups which were subdivided into vitamin E free diet(DM-0E group) 40mg vitamin E per kg diet(DM-40E group) and 400mg vitamin E per kg diet(DM-400E group). Vitamin E level of normal group was 40 mg per kg diet. Diabetes was experimentally induced by intravenous administration of 55 mg/kg B.W of STZ in citrate buffer(pH4.3) after 4 weeks feeding of experimental diets. Animals were sacrificed at the 6th day of diabetic state. The contents of cytochrome P450 in kidney were increased by 82, 54, 41% in DM-0E, DM-40E and DM-400E groups respectively when compared with normal group. The contents of cytochrome b5 in kidney were increased by 28% in DM-0E when compared with normal group but those of DM-40E and DM-400E groups were similar to that of normal group. The activities of NADPH-cytochrome P450 reductase in kidney that were increased by 35% in DM-0E group. Levels of TBARS(thiobarbituric acid reactive substance) in kidney were increased by 207, 129% and 72% in DM-0E and DM-400E groups respectively when compared with normal group but those of DM-40E and DM-400E groups were 26,44% lower than that of DM-0E groups. It is know that the activities of MFO system and lipid peroxidation were inhibited in kidney of STZ-induced diabetic rat by administeration of high doses of vitamin E.(Korean J Nutrition 33(6) : 619~624, 2000)

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Inhibition of Carcinogen-Activating Cytochrome P450 Enzymes by Xenobiotic Chemicals in Relation to Antimutagenicity and Anticarcinogenicity

  • Shimada, Tsutomu
    • Toxicological Research
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    • v.33 no.2
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    • pp.79-96
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    • 2017
  • A variety of xenobiotic chemicals, such as polycyclic aromatic hydrocarbons (PAHs), aryl- and heterocyclic amines and tobacco related nitrosamines, are ubiquitous environmental carcinogens and are required to be activated to chemically reactive metabolites by xenobiotic-metabolizing enzymes, including cytochrome P450 (P450 or CYP), in order to initiate cell transformation. Of various human P450 enzymes determined to date, CYP1A1, 1A2, 1B1, 2A13, 2A6, 2E1, and 3A4 are reported to play critical roles in the bioactivation of these carcinogenic chemicals. In vivo studies have shown that disruption of Cyp1b1 and Cyp2a5 genes in mice resulted in suppression of tumor formation caused by 7,12-dimethylbenz[a]anthracene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, respectively. In addition, specific inhibitors for CYP1 and 2A enzymes are able to suppress tumor formation caused by several carcinogens in experimental animals in vivo, when these inhibitors are applied before or just after the administration of carcinogens. In this review, we describe recent progress, including our own studies done during past decade, on the nature of inhibitors of human CYP1 and CYP2A enzymes that have been shown to activate carcinogenic PAHs and tobacco-related nitrosamines, respectively, in humans. The inhibitors considered here include a variety of carcinogenic and/or non-carcinogenic PAHs and acethylenic PAHs, many flavonoid derivatives, derivatives of naphthalene, phenanthrene, biphenyl, and pyrene and chemopreventive organoselenium compounds, such as benzyl selenocyanate and benzyl selenocyanate; o-XSC, 1,2-, 1,3-, and 1,4-phenylenebis(methylene)selenocyanate.