• Journal of Embryo Transfer
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• v.28 no.2
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• pp.157-162
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• 2013

Methoxychlor (MXC) was developed to be a replacement for the banned pesticide DDT. HPTE [2,2-bis (p-hydroxyphenyl)-1,1,1-trichloroethane], which is an in vivo metabolite of MXC, has strong oestrogenic and anti-androgenic effects. MXC and HPTE are thought to produce potentially adverse effects by acting through oestrogen and androgen receptors. Of the two, HPTE binds to sex-steroid receptors with greater affinity, and it inhibits testosterone biosynthesis in Leydig cells by inhibiting cholesterol side-chain cleavage enzyme activity and cholesterol utilisation. In a previous study, MXC was shown to induce Leydig cell apoptosis by decreasing testosterone concentrations. I focused on the effects of MXC on male mice that resulted from interactions with sex-steroid hormone receptors. Sex-steroid hormones affect other organs including the kidney and liver. Accordingly, I hypothesised that MXC can act through sex-steroid receptors to produce adverse effects on the testis, kidney and liver, and I designed our experiments to confirm the different effects of MXC exposure on the male reproductive system, kidney and liver. In these experiments, I used pre-pubescent ICR mice; the puberty period in ICR mice is from postnatal day (PND) 45 to PND60. I treated the experimental group with 0, 100, 200, 400 mg MXC/kg b.w. delivered by an intra-peritoneal injection with sesame oil used as vehicle for 4 weeks. At the end of the experiment, the mice were sacrificed under anaesthesia. The testes and accessory reproductive organs were collected, weighed and prepared for histological investigation. I performed a chemiluminescence immune assay to observe the serum levels of testosterone, LH and FSH. Blood biochemical determination was also performed to check for other effects. There were no significant differences in our histological observations or relative organ weights. Serum testosterone levels were decreased in a dose-dependent manner; a greater dose resulted in the production of less testosterone. Compared to the control group, testosterone concentrations differed in the 200 and 400 mg/kg dosage groups. In conclusion, I observed markedly negative effects of MXC exposure on testosterone concentrations in pre-pubescent male mice. From our biochemical determinations, I observed some changes that indicate renal and hepatic failure. Together, these data suggest that MXC produces adverse effects on the reproductive system, kidney and liver.

• Korean Journal of Plant Resources
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• v.28 no.5
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• pp.551-560
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• 2015

Here we report the protective activity of cultured Acer tegmentosum cell extract against liver damage in rat intentionally instigated by D-galactosamine. Local fat degeneration and infiltration of inflammatory cells were significantly decreased in cultured A. tegmentosum cell extract administered rat. In addition, acutely increased AST, ALT, LDH, ALP activities and lipid peroxidation and lipid content by liver damage were recovered in experimental rat administrated with A. tegmentosum extract. These results showed that cultured A. tegmentosum cell extract has a role in blood enzyme activation and lipid content restoration within damaged rat liver tissues. Moreover expression rate of TNF-α which accelerates inflammation and induces tissue damage and necrosis was significantly decreased. Also activities of antioxidant enzymes were more effectively upregulated comparing to those of the control group induced hepatotoxicity. All data that cultured A. tegmentosum cell extract has a preventive role against liver damages such as inflammation, tissue necrosis in rats by improving activities of blood enzymes, antioxidant enzymes and modulating expression of inflammation factor, suggest that cultured Acer tegmentosum cell extract is an effective medicinal resource for restoration of hepatotoxicity.

• Korean Journal of Medicinal Crop Science
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• v.10 no.1
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• pp.29-36
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• 2002

Epimedium koreanum Nakai(EKN) has traditionally been well-known as a herbal medicine for the promotion of stamina and the improving sexual activity of human in oriental countries including Korea and China. The aim of this study was to investigate the effect of dietary supplementation of EKN water-extract(0.025%,w/v) on age-related change of xenobiotic metabolizing system in rat liver. Long-term supply of the EKN extract to rats did not induce any discernible signs. However, the mass of liver and kidney were slightly increased by the dietary supplementation. Level of cytochrome P450, NADPH cytochrome P450 reductase, P450 dependent ethoxycoumarin O-deethylase benzphetamine N-demethylase and glutathione-S-transferase in liver were decreased with age, but, these activities in 24 months of age were declined more in rats supplied with EKN extract. Level of cytochrome b5 and NADH-cytochrome b5 reductase were also decreased with age, however, there was no significant difference between with and without EKN extract. These results indicate that long-term supplementation of EKN extract to rats from weaning to 24 months may be a burden on the liver function in old age, and may aggregate the decline of xenobiotic metabolizing enzymes activities in old age.

• Journal of Life Science
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• v.13 no.4
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• pp.457-462
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• 2003

Houttuynia Cordata thunb has been used as folk medicine for analgesics, beriberi, edema, hepatitis and icterus etc. We investigated, the effects of Houttuynia Cordata thunb administration on protective in liver of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) treated rats. Seven days after the injection of TCDD(1${\mu}g$/kg), Houttuynia Cordata thunb (200mg/kg) was administered into rats intraperitoneally for four weeks. We examined the antioxidative enzymatic activity by measuring the level of GOT, GPT in serum and MDA, GSH, GSSG, GPx, SOD and Catalase in liver tissue of rats. GOT activity of Houttuynia Cordata thunb and TCDD administered group(HTT) showed 49.00% of inhibitive effect compared to TCDD-treated abnormal group(TTA). GPT level of HTT group was decreased to the level of Non TCDD-treated group(NTT). MDA content in the TTA group was 1.27 times increased compared to NTT group. HTT group was inhibited by 69.53% compared to TTA group. GSH contents in HTT group was 1.91 times increased compared to TTA group. GSSG contents in HTT group was 46.72% decreased compared to TTA group. SOD and Catalase in TTA group were lower than in NTT group, but SOD and Catalase in HTT group were increased by 82% and 55.45% respectively compared to TTA group.

• Journal of the Korean Society of Food Science and Nutrition
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• v.20 no.2
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• pp.111-120
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• 1991

In order to investigate the cellular peroxidative damage due to heated oil intake and the preventive effect of vitamin E on it rats were fed heated corn oil with acid value of 4.02 at the level of 10 Cal% and three different levels of vitamin E that were 0, 40 and 200 mg/kg diet. Control group was fed fresh corn oil and 40mg/kg diet of vitamin E. After ech feeding period of 0, 3 and 6 weeks, liver superoxide dismutase (SOD), glutathione peroxidase (GPX) activities and microsomal content of vitamin E and lipid peroxide (LPO) were measured as well as cellular morphology was examined. SOD activities and LPO contents were higher, while GPX activities and vitamin e contents were lower in heated oil groups than control group. Electromicroscopic observation revealed the loss of inner mitochondrial membrane and cristae and irregular arrangement of nuclear membrane and chromatin in heated oil groups. As dietary vitamin e level was increased, SOD activity and LPO content were decreased, but GPX activity and vitamin E content in the liver increased and cellular peroxidative damage reduced progressively. This phenomena was more remarkable in 6 weeks of feeding than 3 weeks.

• Korean Journal of Medicinal Crop Science
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• v.8 no.3
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• pp.225-233
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• 2000

There was not noticeable differences in decreasing blood alcohol concentrations between Korea and China-produced Hovenia dulcis $T_{HUNB}$, showing only 1-2 % higher decreasing rate for Korea-produced seed extracts than those from China. It was also found that the blood alcohol decreasing ability was greatly enhanced by partitioning the crude extracts produced from both places. The both extracts (crude and partitioned) accelerated the reducing rate of blood alcohol concentrations down to 1-2 hours, compared to that of control (taking only ethanol). The crude extracts from imported seeds seemed to have slightly better effect on improving in vivo ADH and ALDH activities than domestic ones; however, not for partitioned extracts. It was interesting that the partitioned extracts from both countries enhanced ADH enzyme activity up to 60% than the crude, compared to the control, while ALDH activity was not much affected by the partitioned extracts. It was also confirmed that both ADH and ALDH activities were well balanced in controlling blood alcohol concentration maintaining 28-29% of enzyme activities in vivo. The extracts proved to have better effect on enhancing ALDH activity than ADH activity, which is one of possible explanation that Hovenia dulcis $T_{HUNB}$ can effectively relieve the hangover by fast decreasing acetaldehyde concentration in the liver and blood. GST activity was also increased in the range of 120 to 300% by adding crude or partitioned extracts from both countries; however, there was no difference in enhancing GST activity between the extracts from two countries. The extracts showed competitive inhibition with GST activity, showing the reduction of enzyme activity at higher than 0. 6 (g/L) of the imported extracts.

• Toxicological Research
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• v.6 no.1
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• pp.51-59
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• 1990

Effects of altering hepatic mixed-function oxidase (MFO) enzyme activities on the metabolism and acute toxicity of parathio were investigated in adult female rats. In vitro hepatic metabolism of parathion to paraoxon was increased by phenobarbital pretreatment (50 mg/kg/day, ip, for 4 consecutive days) and SKF 525-A (50 mg/kg, ip, 1 hr prior to sacrifice) decreased paraoxon formation indicating that phenobarbital induces that form(s) of cytochrome P-450 catalyzing conversion of parathion to paraoxon. Degradation of paraoxon to p-nitrophenol was increased by phenobarbital pretreatment, but not affected by SKF 525-A suggesting that MFO activities play only a minor role in the detoxification of the active metabolite of this insecticide. The phenobarbital-induced increase in paraoxon formation was partially antagonized by SKF 525-A. Significant activity for both parathion activation and paraoxon degradation was also observed in the lung preparation, however, this extrahepatic parathion and paraoxon metabolizing activity was not induced by phenobarbital or inhibited by SKF 525-A pretreatment. Phenobarbital pretreatment increased paraoxon level in livers of rats when measured 3 hr following parathion injection (2 mg/kg, ip). SKF 525-A did not alter parathion or paraoxon levels in brain, blood and liver. Phenobarbital pretreatment decreased the toxicity of parathion (4mg/kg, ip) or paraoxon (1.5 mg/kg, ip) as determined by decreases in lethality and inhibition of brain and lung acetylcholinesterases. An additional SKF 525-A treatment failed to decrease the protective effects of phenobarbital against parathion or paraoxon toxicity. These results suggest that some unknown factors other than hepatic MFO induction are involved in the protective action of phenobarbital against parathion and paraoxon toxicity.

• Korean Journal of Pharmacognosy
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• v.30 no.4
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• pp.384-396
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• 1999

Acyl-CoA: Cholesterol Acyltransferase (ACAT) is a key enzyme responsible for cholesteryl ester formation in atherogenesis and in cholesterol absorption from the intestines. In addition under pathological conditions, formation and accumulation of cholesteryl ester as lipid droplets by ACAT within macrophages constitute a characteristic feature of early lesions of atherosclerotic plaques. ACAT inhibitors are expected to be effective for treatment of atherosclerosis and hypercholesterolemia. ACAT inhibitors of natural origin have been rarely reported. In our screening program for ACAT inhibitors, 303 plants were extracted with methanol or ethanol, and screened for the inhibitory activity against ACAT from the rat liver microsome. Extracts of 13 plants including Quercus aliena, Diospyros kaki, Platycarya strobilacea and Hibiscus syriacus inhibited more than 90% of ACAT activity and 43 samples in alcohol extracts such as Magnolia obovata and Panax ginseng also inhibited more than 70% of ACAT activity at a concentration of $100\;{\mu}g/ml$.

• BMB Reports
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• v.40 no.6
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• pp.1077-1082
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• 2007

Human glutamate dehydrogenase exists in hGDH1 (housekeeping isozyme) and in hGDH2 (nerve-specific isozyme), which differ markedly in their allosteric regulation. In the nervous system, GDH is enriched in astrocytes and is important for recycling glutamate, a major excitatory neurotransmitter during neurotransmission. Chloroquine has been known to be a potent inhibitor of house-keeping GDH1 in permeabilized liver and kidneycortex of rabbit. However, the effects of chloroquine on nerve-specific GDH2 have not been reported yet. In the present study, we have investigated the effects of chloroquine on hGDH2 at various conditions and showed that chloroquine could inhibit the activity of hGDH2 at dose-dependent manner. Studies of the chloroquine inhibition on enzyme activity revealed that hGDH2 was relatively less sensitive to chloroquine inhibition than house-keeping hGDH1. Incubation of hGDH2 was uncompetitive with respect of NADH and non-competitive with respect of 2-oxoglutarate. The inhibitory effect of chloroquine on hGDH2 was abolished, although in part, by the presence of ADP and L-leucine, whereas GTP did not change the sensitivity to chloroquine inhibition. Our results show a possibility that chloroquine may be used in regulating GDH activity and subsequently glutamate concentration in the central nervous system.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4367-4375
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• 2016

The objective of the present study was to evaluate the anticancer and radio-sensitizing efficacy of a Withania somnifera extract/Gadolinium III oxide nanocomposite (WSGNC) in mice. WSGNC was injected to solid Ehrlich carcinoma-bearing mice via i.p. (227 mg/kg body weight) 3 times/week during 3 weeks. Irradiation was performed by whole body fractionated exposure to 6Gy, applied in 3 doses of 2 Gy/week over 3 weeks. Biochemical analyses as well as DNA fragmentation were performed. Treatment of solid Ehrlich carcinoma bearing mice with WSGNC combined with ${\gamma}$-radiation led to a significant decrease in the tumor size and weight associated with a significant decrease in mitochondrial enzyme activities, GSH content and SOD activity as well as a significant increase in caspase-3 activity, MDA concentration and DNA fragmentation in cancer tissues. Combined treatment of WSGNC and low dose of ${\gamma}$-radiation showed great amelioration in lipid peroxidation and antioxidant status (GSH content and SOD activity) in liver tissues in animals bearing tumors. It is concluded that WSGNC can be considered as a radio-sensitizer and anticancer modulator, suggesting a possible role in reducing the radiation exposure dose during radiotherapy.