• Journal of Environmental Health Sciences
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• v.27 no.2
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• pp.22-29
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• 2001

To evaluate the cutaneous injury in liver damaged rats by toluene application to the skin, toluene(35mg/㎤) was sequentially applied for 5 days to the dorsal skin of liver damaged rats with $CCl_4$ (6 times ever other day:0.1$m\ell$/100 g body weight-50% $CCl_4$in olive oil). The cutaneous ultrastructural changes were unexoectably not observed in liver from $CCl_4$-treated rats although necrotic liver damage appeared under light microscope. In these animals by the application of toluene to rat skin the cutaneous xanthine oxidase activity was significantly increased(p<0.05), but cytochrome P450 content was not different from that of the control or only $CCl_4$-treated rats. On the other hand, the cutaneous superoxide dismutase and catalase activities in liver damaged animals were significantly respectively(p<0.05, p<0.001), decreased by toluene application to the skin compared with control and especially the former enzyme activity was significantty decreased(p<0.01), compared with that of liver damaged rate rat but glutathione peroxidase, glutathione-S-transferase activities were not significantly different from those of the control or liver damaged rats. Futhermore, the reduced gluathione content of skin was also significantly decreased by toluene application to the liver damaged animals. In conclusion, the great deposits of cerrous peroxide and ultramorphological changes in skin tissue of liver damaged animals by toluene application may be responsible for the oxygen free radical.

• Korean Journal of Veterinary Research
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• v.44 no.4
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• pp.507-513
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• 2004

Aflatoxins are produced mainly by Aspergillus flavus and Aspergillus parasiticus that grow in improperly stored cereals. Aflatoxin B1 ($AFB_1$) is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of $AFB_1$, the relative toxicity of aflatoxins ($AFB_2$ and $AFG_1$) is not fully clarified. Sprague-Dawley male rats were orally administered with $AFB_1$, $AFB_2$, and $AFG_1$ at the dose of 250 ${\mu}g/kg$ (additionally including a dose of $1250{\mu}g/kg $ for $AFB_1$) body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin exposure. Subsequently the immunohistochemical examination of p53, cytochrome p450 1A1 (CYP450 1A1), and glutathione-S-transferase placental form (GST-P) were performed. The level of the 8-OxodG in the liver was determined. Expressions of CYP450 1A1 and p53 were high in the liver of rats through 48 hrs after treatment of $AFB_1$ at the single dose of $250{\mu}g/kg $. This pattern was more clear as increasing doses. The treatment of $AFB_2$ and $AFG_1$ did not affect the expression of CYP450 1A1 but it caused weak expression of p53. The activity of GST were not found in the liver of rats treated with aflatoxins. The formation of 8-OxodG by $AFB_1$ increased in a dose-dependent manner up to 24 hrs after a single treatment of $AFB_1$ thereafter decreased to the level of control. The treatment of $AFB_2$ and $AFG_1$ did not affect the levels of 8-OxodG in the liver of rats with increasing time. These results in the present study indicate that $AFB_1$ among aflatoxins with low comparable levels is the most toxic as determined by early biomarkers such as CYP450 1A1, p53, GST-P, and 8-OxodG.

• Parasites, Hosts and Diseases
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• v.60 no.1
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• pp.39-43
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• 2022

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

• Environmental Analysis Health and Toxicology
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• v.7 no.3_4
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• pp.37-55
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• 1992

Effect of Synethrin on the Toxicity of Dichlorvos in Rats. Hematological, biological and enzymatic effects were investigated in rats treated with DDVP and synethrin. Mutagenicity was also examined. In serological analysis, LDH and ALP were more significantly increased in rats treated with the mixture of DDVP (10mg/kg) and synethrin (250mg/kg) than with either DDVP or synethrin. DDVP alone slightly increased cytochrome P-450 in the liver while synethrin or the mixture decreased it. Lipid peroxidation was significantly increased in the liver when rats were treated with both DDVP and the mixture. Cholinesterase activity was significantly decreased in the liver and serum when treated with DDVP as well as with the mixture. In mutagenicity test, DDVP was shown to be weakly positive to TA 97a, TA 100 and TA 102, but negative to TA 1537. Synethrin showed negative in all strains tested. These results suggest that the mixture of DDVP and synethrin increased the toxicities but not the mutagenicity.

• Environmental Analysis Health and Toxicology
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• v.19 no.3
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• pp.251-259
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• 2004

Xenoestrogens are chemicals with diverse structure that mimic estrogen. Bisphenol A, a monomer of polycarbonate and epoxy resins, has been detected in canned food and human saliva. Bisphenol A stimulate cell proliferation and induce expression of estrogen -response genes in vitro. The purpose of the this study was to evaluate cell proliferation of bisphenol A in the presence of a rat liver 59 mix contaning cytochrome P450 enzymes and Cu (II). The fragmentation of intact DNA, a parameter of apoptotic cell death, was evaluated quantitatively by diphenylamine reaction method. Bisphenol A induced apoptotic cell death in a dose-dependent manner The effect of radical scavenger on the apoptotic cell death induced bisphenol A was investigated. The DNA fragmentation induced by bisphenol A was significantly inhibited by addition of radical scavenger to the culture medium. This indicated that elevated oxidative stress caused by imbalance between the production and removal of free radicals occurred in cells. Taken together, these results suggest that free radical reacts with Cu (II) leading oxidative stress.

• Toxicological Research
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• v.31 no.1
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• pp.25-32
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• 2015

The objectives of this study were to investigate the individual characteristics, lifestyle habits, exposure levels, and genetic diversity of xenobiotic-metabolizing enzymes involved in toluene metabolism in Korean and foreign workers exposed to toluene at a manufacturing plant. This study was conducted to determine the effects of culture or ethnicity on toluene metabolism. The results showed that blood and urinary toluene concentrations were dependent on the level of exposure to toluene. We analyzed the correlation between toluene metabolism and genetic diversity in glutathione S-transferase (GST) (M1), GSTT1, and cytochrome p-450 (CYP) $2E1^*5$ as well as lifestyle habits (smoking, drinking, and exercise habits). The results revealed significant correlations between toluene metabolism and GSTM1 and GSTT1 genetic diversity, as well as smoking and exercise.

• Environmental Analysis Health and Toxicology
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• v.18 no.3
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• pp.175-182
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• 2003

Bisphenol A shares similarities in structure, metabolism and action with DES, a known human teratogen and carcinogen. Bisphenol A, a monomer of polycarbonate and epoxy resins, has been detected in canned food and human saliva. The purpose of the this study was to evaluate the cytotoxicity, cell proliferation of bisphenol A In the presence of a rat liver S9 mix, contaning cytochrome P450 enzymes, and Cu (II). In the present study, Bisphenol A in combination with Cu (II) exhibited a enhancement in cytotoxicity which were inhibited by free radical scavengers. The content of malondialdehyde, an end product of lipid peroxidation, was also found to increase with concentration of bisphenol A. Also, we examined the change of CuZn-SOD, Mn-SOD, catalase and GPx activities in the MCF-7 cells exposed to bisphenol A. The activities of CuZn-SOD, CPx, catalase were found to decrease with bisphenol A concentration. Meanwhile, the activity of Mn-SOD was unchanged. This indicated that elevated oxidative stress caused by imbalance between the production and removal of free radicals occurred in cells.

• YAKHAK HOEJI
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• v.54 no.2
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• pp.97-101
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• 2010

Recently, it was found that the formation of reactive metabolites by cytochrome P450s as well as the depletion of glutathione would play important roles in hepatotoxicity induced by 1-bromopropane. In the present study, possible roles of anti-oxidants in 1-bromopropane-induced hepatotoxicity were investigated in male ICR mice. The hepatotoxicity induced by 1-bromopropane was significantly protected by the co-treatment with either N-acetyl cysteine or silymarin. 1-Bromopropane-induced decrease in hepatic glutathione level was significantly protected by the pretreatment with N-acetyl cysteine. Taken together, the present results indicated that the reduction of hepatic glutathione level caused by 1-bromopropane treatment might be associated in 1-bromopropane-induced hepatotoxicity in mice.

• Preventive Nutrition and Food Science
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• v.3 no.1
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• pp.67-70
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• 1998

To investigate an effect of Gam-Roa tea on the free radical or alcohol detoxicating enzyme activities, the rats got a drink at the Gam-Roa tea instead of water for 3 months, and then the animals were sacrificed and obtained the following findings. The animals receiving Gam-Roa tea showed a decreasing tendency of hepatic xanthine oxithine oxidase activity and significantly incresed content of cytochrome P-450 compared with the control. Furthermore, hepatic superoxide dismutase and glutathione S-transferase activities were also more increased in rats received Gam-Roa tea than in the control group, those receiving water. On the other hand, alcohol or aldehyde dehydrogenase activities were more increased in rats receiving Gam-Roa tea than the control. In conclusion, it is likely that the liver of rats receiving Gam-Roa tea may have the oxygen free radical or alcohol detoxication potential.

• Biomolecules & Therapeutics
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• v.10 no.4
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• pp.211-217
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• 2002

Hepatoprotective activity of methanol extract of Angelica tenuissima Nakai on the $CCl_4$-induced hepatotoxicity was investigated. To elucidate the hepatoprotective activity and free radical scavenging effect, we examined alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, total protein, cholesterol, malondialdehyde (MDA) levels in serum and activities of superoxide dismutase (SOD), catalase (CAT) in hepatic tissue as compared with those of carbon tetrachloride-induced rats. The action mechanism also has been estimated by quantative analysis of cytochrome P450 (CYP), NADPH-CYP reductase for phase I metabolism and glutathion (GSH), glutathion S-transferase (GST) level for phase II metabolsim. Treatment of Angelica tenuissima methanol extract significantly lowered the levels of alanine aminotransferase and aspartate aminotransferase. In addition, the levels of cholesterol, triglyceride, MDA, CAT were decreased, and SOD was activated. This result indicates that the hepatoprotective effect of Angelica tenuissima methanol extract on the CCl4-induced hepatotoxicity would be originated from reduction of the NADPH-CYP reductase, GSH and the enhancement of the activities of GST, CYP.