• Preventive Nutrition and Food Science
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• 제8권2호
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• pp.130-136
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• 2003

The protective effects of onion extract (OE), onion powder extracted in ethanol for 2 days. on carbon tetrachloride ($CCl_4$)-induced hepatotoxicities and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with OE prior to the administration of $CCl_4$ significantly reduced the increase in serum alanine and aspartate aminotransferase activities and hepatic lipid peroxidation in a dose-dependent manner. In addition, pretreatment with OE significantly prevented the depletion of reduced glutathione content in the liver of $CCl_4$-intoxicated mice. $CCl_4$-induced hepatotoxicity was also prevented, as indicated by a liver histopathologic findings. The effects of OE on the cytochrome P450 (P450) 2E1, the major isozyme involved in $CCl_4$ biotransformation were investigated. Treatment of mice with OE resulted in a significant decrease in P450 2E1-dependent p-nitrophenol and aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the P450 2E1 expressions were also decreased, as determined by immunoblot analysis. OE also exhibited antioxidant effects in FeCl$_2$-ascorbate induced lipid peroxidation in rat liver homogenates and in superoxide radical scavenging activity. These results show that the protective effects of OE against the $CCl_4$-induced hepatotoxicity may be due to its ability to block bioactivation of $CCl_4$, mainly tty inhibiting the expression and activities of P450 2E1 and by scavenging free radicals.

• 대한수의학회지
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• 제35권3호
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• pp.437-445
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• 1995

과일 및 채소류의 곰팡이 억제제로 개발된 captafol은 인간 및 동물에서의 독성작용은 많이 보고된 바 있으나 이들의 독작용을 완화시키거나 치료할 수 있는 제제에 대한 연구는 별로 알려진 바 없다. captafol에 의한 혈액학 및 혈청 생화화적 변화에 따른 cysteine의 방어 작용을 확인할 목적으로 랫트에 5mg/kg 용량의 captafol을 1회 복강 투여하고 동시에 5, 58, 290 및 580mg/kg cysteine을 각각 투여하고 체중의 변화, 부검소견, 절대장기중량, 혈액학 및 혈청 생화학적 소견을 비교 분석 하였다. captafol 단독 투여군에서는 체중 및 간 장기중량 감소, 복강내 장기들의 섬유소에 의한 유착 및 복수 등이 현저하였으며 적혈구 수, hemoglobin 농도, 혈청 AST의 증가가 인정되었으며 또한 혈청 인지질 함량 감소가 확인되었다. 한편, cysteine 58mg/kg 이상의 용량군에서는 복강내 장기들의 유착 및 복수가 확인되지 않았으며 장기중량, 혈액학 및 혈청 생화학적 소견에서도 정상을 나타내었다. 이 연구 결과는 captafol의 중독증상에 대해 cysteine 및 sulfhydryl군을 가진 물질은 그 증세를 감소시키거나 완화시킬 수 있는 효과가 있음을 보여주고 있다.

• Nutrition Research and Practice
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• 제10권1호
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• pp.19-25
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• 2016

BACKGROUND/OBJECTIVES: Cadmium is a toxic metal that is an occupational and environmental concern especially because of its human carcinogenicity; it induces serious adverse effects in various organs and tissues. Even low levels of exposure to cadmium could be harmful owing to its extremely long half-life in the body. Cadmium intoxication may be prevented by the consumption of dietary components that potentially reduce its accumulation in the body. Dietary chitosan is a polysaccharide derived from animal sources; it has been known for its ability to bind to divalent cations including cadmium, in addition to other beneficial effects including hypocholesterolemic and anticancer effects. Therefore, we aimed to investigate the role of dietary chitosan in reducing cadmium accumulation using an in vivo system. MATERIALS/METHODS: Cadmium was administered orally at 2 mg (three times per week) to three groups of Sprague-Dawley rats: control, low-dose, and high-dose (0, 3, and 5%, respectively) chitosan diet groups for eight weeks. Cadmium accumulation, as well as tissue functional and histological changes, was determined. RESULTS: Compared to the control group, rats fed the chitosan diet showed significantly lower levels of cadmium in blood and tissues including the kidneys, liver, and femur. Biochemical analysis of liver function including the determination of aspartate aminotransferase and total bilirubin levels showed that dietary chitosan reduced hepatic tissue damage caused by cadmium intoxication and prevented the associated bone disorder. CONCLUSIONS: These results suggest that dietary chitosan has the potential to reduce cadmium accumulation in the body as well as protect liver function and bone health against cadmium intoxication.

• Radiation Oncology Journal
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• 제32권2호
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• pp.77-83
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• 2014

Purpose: To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases. Materials and Methods: Sixteen patients received whole liver radiotherapy (WLRT) between January 1997 and June 2013. A total dose of 21 Gy was delivered in 7 fractions. Results: The median survival time after WLRT was 9 weeks. In univariate analysis, performance status, serum albumin and total bilirubin level, liver volume and extrahepatic metastases were associated with survival. The mean liver volume was significantly different between subgroups with and without pain relief (3,097 and 4,739 mL, respectively; p = 0.002). Conclusion: A larger liver volume is a poor prognostic factor for survival and also a negative predictive factor for response to WLRT. If patients who are referred for WLRT have large liver volume, they should be informed of the poor prognosis and should be closely observed during and after WLRT.

• 대한의생명과학회지
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• 제12권4호
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• pp.361-370
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• 2006

To evaluate an effect of pathological liver damage on the conjugation of cyclohexane metabolites, rats were pretreated with 50% $CCl_4$ dissolved in olive oil (0.1 ml/100 g body weight) 10 or 17 times intraperitoneally at intervals of every other day. On the basis of liver function, the animals pretreated with $CCl_4$ 10 times were identified as acutely liver damaged ones and the animals pretreated with $CCl_4$ 17 times were identified as severly liver damaged ones. To these liver damaged animals, cyclohexane (a single dose of 1.56 g/kg body weight, i.p.) was administered at 48 hr after the last injection of $CCl_4$. The rats were sacrificed at 4 or 8 hr after injection of cyclohexane. The cyclohexane metabolites, cyclohexanol (CH-ol), cyclohexane-1,2-diol (CH-1,2-diol), cyclohexane-1,4-diol (CH-1,4-diol), and their glucuronyl conjugates and cyclohexanone were detected in the urine of cyclohexane treated rats. The urinary concentration of cyclohexane metabolites was generally more increased in liver damaged animals than normal ones, and the increasing rate was higher in $CCl_4$ 17 times injected rats than 10 times injected ones. And liver damaged.ats, especially $CCl_4$ 17 times treated ones, had an enhanced ability of glucuronyl conjugation to CH-ol analogues compared with normal group. Futhermore, CH-1,2 and 1,4-diol were all conjugated with glucuronic acid in $CCl_4$ 17 times injected animals. On the other hand, the increasing rate of activities of hepatic cytochrome P450 dependent aniline hydroxylase, alcohol dehydrogenase and urine diphosphate glucuronyl transferase was higher in 17 times $CCl_4$-treated rats compared with normal and $CCl_4$ 10 times injected animals. Taken all together, it is assumed that an increased urinary excretion amount of cyclohexane metabolites in liver damaged rats might be caused by an increase in the activities of cyclohexane metabolizing enzymes. And enhanced conjugating ability of CH-ol in liver damaged animals and novel finding of conjugating form of CH-1,2 and 1,4-diol might be caused by increase in the activity of hepatic diphosphouridine glucuronyltransferase.

• Journal of Pharmaceutical Investigation
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• 제31권4호
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• pp.209-216
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• 2001

The purpose of the present study was to investigate the hepatic uptake and biliary excretion of l-anilino-8-naphthalene sulfonate (ANS) in vivo. The plasma concentration and liver concentration of ANS were determined after its i.v. bolus administration at a dose of $30\;{\mu}mol/kg$ in rats. The hepatic uptake clearance $(CL_{uptake})$ of ANS was 0.1 ml/min/g liver. On the basis of the unbound concentration of ANS, the permeability-surface area product $(PS_{influx})$ was calculated to be l0.4 ml/min/g liver, being comparable of in vitro data. On the other hand, we determined the plasma concentration, liver concentration and biliary excretion rate of ANS at steady-state after its i. v. infusion $(0.2-1.6\;{\mu}mol/min/kg)$ in rats. The excretion clearance $(CL_{excretion})$ of ANS showed Michaelis-Menten kinetics with increasing the infusion rate. The permeability-surface area product $(PS_{excretion})$ based on the unbound concentration in the liver was calculated to be 0.0165 ml/min/g liver, which is negligible compared with the intrinsic clearance $(CL_{int}=3.3\;ml/min/g\;liver)$ by rat liver microsomes. The sequestration process of ANS, therefore, was considered to be mainly due to the metabolic process in the liver $(PS_{seq}{\risingdotseq}CL_{int})$. Furthermore, $PS_{efflux}$ value calculated from $PS_{influx}$ and $PS_{seq}$ was 4.4 ml/min/g liver, which was comparable of in vitro data. In conclusion, in vivo parameters such as $PS_{influx}$, $PS_{efflux}$ and $PS_{seq}$ in the present study showed good in vivo-in vitro relationship. Thus, the kinetic analysis method proposed in the present study would be useful to analyze the hepatic transport of drugs in vivo.

• Asian-Australasian Journal of Animal Sciences
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• 제11권5호
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• pp.545-549
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• 1998

The influence of refeeding with either vitamin, mineral, fibre of water on protein synthesis and mRNA content in the liver and breast muscle of fasted chicks was investigated. At 15 d of age, chicks were fasted for 2 d and then refed either vitamin, mineral, fibre or water. The fractional synthesis rate (FSR) of protein was measured after 30 min of refeeding by using a large dose injection of L - 2, $6[^3H]$ phenylalanine. In the liver, FSR was reduced by fasting and tended to increase but not significantly by refeeding with vitamin or mineral. FSR was not affected by refeeding with fibre or water. There was no influence of fasting and refeeding on ribosomal capacity (the RNA : protein ratio) and ribosomal efficiency (total protein synthesised per total RNA). The absolute synthesis rate (ASR) of liver protein and hepatic mRNA content were reduced by fasting and unchanged by refeeding. In the muscle, FSR, ASR and mRNA content were significantly decreased by fasting and not recovered by refeeding with either vitamin, mineral, fibre or water. It concluded that vitamin, mineral, fibre and water have little capacity to stimulate liver and muscle protein synthesis reduced by fasting.

• Advances in Traditional Medicine
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• 제1권1호
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• pp.28-36
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• 2000

Effects of hesperetin and naringenin on the concentration of triacylglycerol in the serum and liver were studied in male golden hamster fed with the semipurified diet containing at 1% level of them for 3 weeks. The concentration of triacylglycerol in serum of the naringenin group decreased by 31%, whereas that in liver increased by 37% compared to the control group. The concentration of triacylglycerol in the serum and liver of the hesperetin group was slightly lower than the control group. The activity of microsomal phosphatidate phosphohydrolase in the liver, which is a key enzyme for biosynthesis of triacylglycerol, was significantly inhibited in the hesperetin group, whereas it was not affected in the naringenin group. The effect of hesperetin on phosphatidate phosphohydrolase was also measured in vitro. Hesperetin decreased the activity of phosphatidate phosphohydrolase with a dose-dependent manner. Both naringenin and hesperetin did not statistically affect the daily food consumption, body weight, liver weight, and total cholesterol in the serum. The observation accounts for the hypotriglyceridemic effect of hesperetin in the hyperlipidemic hamster.

• 대한한방내과학회지
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• 제21권1호
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• pp.108-115
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• 2000

Objective : To investigate the hepatoprotective effects of Gami-oryungsan on the liver damage induced by bromobenzene. Method : The development of fibrosis and acute liver injury was examined by the chemical analysis of AST, AL T, ${\gamma}$-GTP . and epoxide hydrolase glutathione S-transferase glutathione peroxidase enzyme activity, lipidoperoxide levels, glutathione levels were measured and oberved. Results : The increasing levels of lipidoperoxide was decreased proportionally according to dose of extract GO. Epoxide hydrolase glutathioneS-transferase glutathione peroxidase enzyme activity highly increased in GO pre-acupunctured group compared with the group treated with only bromobenzene. The increase of serum AST, AL T, ${\gamma}$-GTP enzyme activity of mice by bromobenzene was inhibited by the administration of GO. Lipidoperoxide levels in rat's liver decreased compared to the case of bromobenzene-treated group. The levels of Glutathione decreased by bromo benzene were increased highly in GO pre-acupunctured group. Conclusion : These results suggest that GO extract recovers the damage of liver due to bromobenzene intoxication by decreasing the lipid peroxidation AST AL T ${\gamma}$-GTP enzyme activity and increasing epoxide hydrolase glutathioneS-transferase glutathione peroxidase enzyme activity, glutathione levels.

• 한국환경성돌연변이발암원학회지
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• 제25권3호
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• pp.97-103
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• 2005

The genotoxic effect of antimalarial drugs amodiaquine (AQ), mefloquine (MQ) and halofantrine (HF) was investigated in.at liver cells using the alkaline comet assay. AQ, MQ and HF at concentrations between $0-1000{\mu}mol/L$ significantly increased DNA strand breaks of rat liver cells dose-dependently. The order of induction of strand breaks was AQ>MQ>HF. The rat liver cells exposed to AQ and HF (200 and 400 ${\mu}mol/L$) and treated with (Fpg) the bacterial DNA repair enzyme that recognizes oxidized purine showed greater DNA damage than those not treated with the enzyme, providing evidence that AQ and HF induced oxidation of purines. Such an effect was not observed when MQ was treated with the enzyme. Treatment of cells with catalase, an enzyme inactivating hydrogen peroxide, decreased significantly the extent of DNA damage induced by AQ, and HF but not the one induced by MQ. Similarly quercetin, an antioxidant flavonoid at $50{\mu}mol/L$ attenuated the extent of the formation of DNA strand breaks by both AQ and HE. Quercetin, however, did not modify the effects of MQ. These results indicate the genotoxicity of AQ, MQ and HF in rat liver cells. In addition, the results suggest that reactive oxygen species may be involved in the formation of DNA lesions induced by AQ and HF and that, free radical scavengers may elicit protective effects against genotoxicity of these antimalarial drugs.