• Journal of Veterinary Clinics
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• v.14 no.1
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• pp.24-29
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• 1997

흰쥐 간정맥 및 간문맥에 PE10 튜브를 마취하에 이식시킨 후 5일째부터 고형사료와 10% creatine을 함유한 고형사료를 5일 동안 섭식 시켜 급속 냉동 시켰다. 냉동시킨 흰쥐 간장, 뇌 및 근육에서 creatine을 포함한 간장 metabolites을 조사하여 다음과 같은 결과를 얻었다. 또한 간장세포내의 water compartment의 변화를 동시에 실시 하였다. Creatine을 섭식시킨 실험군은 정상 대조군과 비교하여 섭식에 의한 간세포내의 water compartment 에 벼노하를 주지 않았고 간장 세포내의 creatine농도에 있어서는 약 43배 이상 세포내 증가를 유도하였으며, 이는 세포외 및 세포내의 creatine의 gradient에 의해 영향을 받고 있음을 알 수가 있었고, 또한 동시에 뇌, 근육 등에서는 섭식에 의해 유의성 있는 농도 변화는 보이지 않았다. 이는 세포 외액속에 함유된 creatine 이 여러 수송기전에 의하여 간세포내로 흡착이 이루어진 것을 알 수 있었으나, 간세포 분리 시험법에로 Creatine Kinase 효소 활성도를 측정한 결과 non-parenchymal hepatocytes에서만 거의 100% 효소 활성도가 있음을 증명 하였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.98-98
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• 1997

This study was done to investigate the effect of vitamin E on hypoxia/reoxygenation-induced hepatic injury in isolated perfused rat liver. Rats were pretreated with vitamin E or vehicle(soybean oil). Isolated livers from fasted 18 hours were subjected to 45min of low flow hypoxia or N$_2$ hypoxia followed by reoxygenation for 30min. The perfusion medium used was KHBB(pH 7.4) and 50${\mu}$㏖/$\ell$ of ethoxycoumarin was added to the perfusate to determine the ability of hepatic drug-metabolizing systems, In low flow hypoxia model, total glutathione and oxidised glutathione levels were significantly increased by hepoxia/reoxygenation with slight increase in LDH levels. These increases were prevented by vitamin E pretreatment. In N$_2$ hypoxia model, LDH, total glutathione and oxidized glutathione levels were increased significantly by hypoxia but restored to normal level by reoxygenation. Vitamin E had little effect on this hypoxic damage. There were no significant changes in the rate of hepatic oxidation of 7-EC to 7-HC in both hepoxic models. But, the subsequent conjugation of 7-HC by sulfate or glucuronic acid were significantly decreased by hypoxia, but restored by reoxygenation in both hypoxia models. As opposed to our expectation, treatment with vitamin E aggrevated the decrease of the rate of conjugation and even inhibited the restoration by reoxygenation. Our findings suggest that hypoxia/reoxygenation diminishes phase II drug metabolizing function and this is, in part, related to decreased energy level.

• Archives of Pharmacal Research
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• v.20 no.5
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• pp.471-475
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• 1997

Livers isolated from 18 hours fasted rats were subjected to N$_{2}$ hypoxia (for 45 min) followed by reoxygenation (for 45 min). The perfusion medium used was Krebs-Henseleit bicarbonate buffer (KHBB, pH 7.4). Lactate and alanine were added as gluconeogenic and ureagenic substrates and Trolox C was also added to perfusate. Oxygen consumption, lactate dehydrogenase (LDH), alanine transaminase (ALT), total glutathione, oxidized glutathione, bile flow, glucose and urea were measured. After hypoxia oxygen consumption significantly dropped but Trolox C had no influence on this decrease. ALT and LDH were significantly increased by hypoxia/reoxygenation. This increase was markedly attenuated in the presence of Trolox C. The total glutathione and oxidized glutathione efflux increased following hypoxia, which were prevented by the treatment of Trolox C. Bile flow rate decreased following hypoxia/reoxygenation but did not continue to decrease in the reoxygenation phase by Trolox C. Following hypoxia/reoxygenation glucose and urea releases decreased. Trolox C had no influence on inhibition of glucose and urea production. These results suggest that Trolox C protected the liver cells against hypoxia/reoxygenation injury, yielding further evidence for a causative role of oxidative stress in this model.

• The Korean Journal of Nuclear Medicine
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• v.19 no.1
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• pp.145-148
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• 1985

A small number of pathologic entities such as Budd-Chiari Syndrome, cirrhosis, focal nodular hyperplasia, and superior and inferior vena cava obstruction has been reported to result in focal areas of increased uptake of radiocolloid on the hepatoscintigram. We recently studied a patient with focal accumulation of $^{99m}Tc-phytate$ at the inferior aspect of the liver, at the junction of the right and left lobe. The superior vena cava scintiangiogram was taken for the evaluation of the superior vena cava obstruction and collateral circulations. As a result of superior vena caval obstruction a considerable amount of blood flowed to the liver through the anterior parietal and periumblical venous channels. A certain fraction of radiocolloid delivered by the rete mirabile perfused to a localized area of the liver. This would explain the hot spot around the porta hepatis in this case.

• YAKHAK HOEJI
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• v.42 no.4
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• pp.422-430
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• 1998

In order to study the effects of Rhei rhizoma, Ephedrae herba and Scutellariae radix on hepatic metabolism, we examined the pretreatment effect of those on the metabolism of 7-e thoxycoumarin (EC). Water extracts (1g/kg) of Rhei rhizoma, Ephedrae herba and Scutellariae radix were administered orally to rats for 7 days, respectively. Livers were then isolated and perfused with 100mcM EC for 2 hours. The metabolites of EC, 7-hydroxycoumarin, sulfate conjugate and glucuronide conjugate were measured in the perfusates. The amount of glucuronide conjugates was decreased in Rhei rhizoma pretreated rats (p<0.01), however, 7-hydroxycoumarin was increased in Ephedrae herba pretreated rats (p<0.01). We examined whether the change of enzyme activity is related to the change of cytochrome P4501A1 and P4502B1 mRNA level in the perfused rat liver, which are responsible for EC metabolism. CYP1A1 and CYP2B1 mRNA level was increased, which was was not statistically significant with rhei rhizoma nor ephedrae herba pretreatment. We also assessed the hepatotoxicity of Rhei rhizoma, Ephedrae herba and Scutellariae radix. The activities of ALT and AST were assayed at 24 hours after 7 days administration. Only the ratio of ALT over AST was increased in ephedrae herba pretreated rats (p<0.05). Lipid peroxidation was increased in Rhei rhizoma treatment (p<0.05), while histopathological examination performed after liver perfusion did not show any difference compared with vehicle treatment. These results suggest that Ephedrae herba pretreatment increases the o-deethy-lation of 7-ethoxycoumarin in rats, which may be mediated by CYP1A1 mRNA induction.

• Korean Journal of Veterinary Research
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• v.40 no.2
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• pp.267-274
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• 2000

Since intracellular free $Mg^{2+}$ ($[Mg^{2+}]_i$) appears to be tightly regulated following cellular energy depletion, we hypothesized that the increase in $[Mg^{2+}]_i$ would result in $Mg^{2+}$ extrusion into circulation. Extracellualr $Mg^{2+}$ contents ($[Mg^{2+}]_o$) were measured in rat erythrocytes, the perfused heart and liver, and plasma in the anesthetized rat. Animals were injected intraperitoneally with sodium nitrite ($NaNO_2$) and plasma $Mg^{2+}$ was measured after the injection and then 10 and 20 minutes later. An increase in circulating (plasma) $Mg^{2+}$ ($[Mg^{2+}]_c$) and methemoglobin was observed in animals injected with $NaNO_2$ (30 mg/Kg). The time course of the effects demonstrated that $[Mg^{2+}]_c$ and methemoglobin continued to increase 10 minutes after the $NaNO_2$ injection. Under these conditions, there was a sustained increase in $[Mg^{2+}]_c$, but not in methemoglobin, which was inhibited by pretreatment with potassium cyanide (KCN, 4 mg/Kg), indicating that an increase in $[Mg^{2+}]_c$ was accompanied by ATP depletion. Injection of rotenone (0.9 mg/Kg) or 2,4-dinitrophenol (15 mg/Kg) also induced an increase in $[Mg^{2+}]_c$. Reduced respiration rate from 100/min to 10/min during 30 minutes also caused a time-dependent rise in $[Mg^{2+}]_c$. These increase in $[Mg^{2+}]_c$ were inhibited by pretreatment with KCN. In addition, ATP depletion by $NaNO_2$ or KCN sustainedly increased the $[Mg^{2+}]_o$ in rat erythrocytes. $Mg^{2+}$ efflux was stimulated by KCN in the perfused heart and liver, but not by $NaNO_2$. These results suggest that the activation of $Mg^{2+}$ effluxes into the circulation is directly dependent on the ATP depletion-induced increase in $[Mg^{2+}]_i$ and heart, liver and erythrocytes have a major pool of $Mg^{2+}$ that can be mobilized upon cellular energy state.

• International Journal of Industrial Entomology and Biomaterials
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• v.12 no.1
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• pp.1-5
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• 2006

Cordyceps, one of the well-known traditional Chinese medicines, consists of the dried fungus C. sinensis growing on the larva of caterpillar. It is commonly used as a tonic of restoring vital body functions. In order to evaluate the pharmacological effects of C. militaris, the anti-oxidation and antiaging effect of cultured C. militaris growing on pupa of silkworm Bombyx mori, were investigated. The results showed! that the contents of lipofusin in myocardium were reduced and the SOD activity in the liver were elevated in a dose-dependent manner while no effect was observed for blood GSH-Px activity and liver MDA content in mice perfused with the cultured C. militaris compared to those untreated mice. Furthermore, the average life span, maximum life span and 50% death time of the fruit flies treated with cultured C. militaris were markedly prolonged. The results suggest that the cultured C. militaris growing on pupa of silkworm possesses anti-oxidation and delay senescence activity.

• KSBB Journal
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• v.16 no.1
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• pp.24-29
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• 2001

Recently hepatocyte-based bioartificial liver (BAL) and hepatocyte transplantation have been actively investigated to treat acute hepatic failure. The BAL acts as a bridge to provide patients with more time until a donor organ becomes available for transplantation or until their own liver can be regenerated. In this study, we manufactured a polyurethane foam (PUF) using 15% NCO-prepolymer with a pore opening that allows it to be used as a hepatocyte immobilizing material. Cubes of PUF (3 mm dim.) were seeded with rat primary hepatocytes at a density of 5.5$\pm$1.1$\times$ $10^6$ cells/$cm^3$ PUF by centrifuging them together. The cell laden PUF cubes were packed into a prototype reactor and perfused with a hormonally defined medium for a week. Hepatocytes in the pores of the PUF formed spheroids that showed stable ammonia removal and urea synthesis activities. The albumin production level was comparable to other BAL systems. The PUF packed hepatocyte bioreactor has the potential to be used as a BAL.

• Korean Journal of Acupuncture
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• v.23 no.4
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• pp.169-176
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• 2006

Objectives : This study was designed to compare the effects of tonification and sedation methods of Liver Meridian in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mice model. Methods : We injected MPTP (30 mg/kg, i.p.) or saline for 5 consecutive days. Acupuncture treatments were given to the mice with MPTP at LR8 and LR4 to tonify Liver Meridian (Liver+) or LR4 and LR2 to sedate it (Liver-) for 12 day. At the 12th day after first injection, mice were perfused, and then tyrosine hydroxylase (TH)-immunohistochemistry was performed in substantia nigra (SN) of their brains. After counting the number of TH-positive neurons, we compared their numbers among experimental groups. Results : The number of TH-positive neurons of Liver+ group was significantly increased compared to that of MPTP group in the SN. That of Liver-group was also increased more than MPTP group, but not significantly. Conclusions : Tonifying Liver Meridian might be effective therapeutic tools for the neuroprotection in subchronic MPTP-induced mice model.

• Archives of Pharmacal Research
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• v.23 no.5
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• pp.495-500
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• 2000

We investigated whether S-adenosylmethionine (SAM) treatment improved ischemic injury using perfused rat liver after sequential periods of 24 h cold and 20 min re-warming ischemia. SAM (100 $\mu\textrm{mol/L}$) was added to University of Wisconsin (UW) solution and Ringers lactate solution. After cold and sequential warm ischemia, releases of lactate dehydrogenase (LDH) and purine nucleoside phosphorylase (PNP) markedly increased during repefusion. The increase in PNP was significantly reduced by SAM treatment. While the concentration of reduced glutathione (GSH) in ischemic livers significantly decreased, the concentration of glutathione disulfide (GSSG) increased. This decrease in GSH and increase in GSSG were suppressed by SAM treatment. Lipid peroxidation was elevated in cold and warm ischemic and reperfused livers, but this elevation was also prevented by SAM treatment. Hepatic ATP levels were decreased in the ischemic and reperfused livers to 42% of the control levels. However, treatment with SAM resulted in significantly higher ATP levels and preserved the concentration of AMP in ischemic livers. Our findings suggest that SAM prevents oxidative stress and lipid peroxidation and helps preserve hepatic energy metabolism.