• Biomolecules & Therapeutics
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• v.6 no.3
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• pp.283-288
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• 1998

YH 1885 (5,6-dimethyl -2-(4-fluorophenylamino)-4-(1-methyl -1,2,3,4-tetrahydroisoquinolin -2- yl) pyrimidine hydrochloride) was developed as an antiulcer drug. The objective of this study was to examine a comparative metabolism of YH1885 in rat, dog, monkey and human liver tissues and to determine the metabolite profiles produced by the four species. YH1885 was metabolized by liver 59 fractions from all four species. Control incubations containing 59 fraction but no cofactors, contained essentially no metabolites. Metabolism of YH1885 apparently became saturated in the concentration range studied because the % of YH 1885 metabolized decreased with increasing drug concentration for all four species. Six to nine metabolite peaks were detected in the incubations and the particular profile of metabolites varied with species. The total amount of metabolites formed by liver microsomes from human and monkey were less than microsomes from rat or dog. The major metabolite peak formed by rat liver 597actions fluted near the solvent front on the HPLC or remained at the origin in TLC, indicating that it contained one or more polar metabolites. Dog liver 59 fractions incubations contained four major metabolites that each accounted for about 15 to 20 % of the total radioactivity at the low concentration of YH1885. The metabolite profiles of YH1885 appeared to be similar in incubations with rhesus monkey and human liver 59 fraction. The amount of metabolites formed by rhesus monkey liver preparations was greater than that of human liver that contained prominent metabolite peaks with approximate relative retention time of 0.14 and 0.43.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.397-415
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• 2002

This paper deals with a crucial mechanism for interaction of basic drugs and cardiac glycosides at the hepatic uptake level. Available literature data is provided and new material is presented to picture the differential transport inhibition of bulky (type2) cationic drugs by a number of cardiac glycosides in rat liver. It is shown that the so called organic anion transporting peptide 2 (oatp2) is the likely interaction site: differential inhibition patterns as observed in oocytes expressing oatp2, could be clearly identified also in isolated rat hepatocytes, isolated perfused rat liver and the rat in vivo. The anticipation of transport interactions at the hepatic clearance level should be based on data on the relative affinities of interacting substrates for the transport systems involved along with knowledge on the pharmacokinetics of these agents as well as the chosen dose regimen in the studied species. This review highlights the importance of multispecific tranporter systems such as OATP, accommodating a broad spectrum of organic compounds of various charge, implying potential transport interactions that can affect body distribution and organ clearance.

• Archives of Pharmacal Research
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• v.20 no.3
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• pp.239-246
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• 1997

In the present study, liver regeneration rate (%) was increased up to 70% 3 days after partial hepatectomy (PH). Nitric oxide synthase (NOS) activity in liver tissue as well as serum nitrite/ nitrate content had no timed response, revealing no significant difference between shamoperated and partially hepatectomized rat liver. Contents of free methylarginines in liver tissue were increased biphasically in a time-dependent manner after PH. However, those in serum did not exhibit the same patterns as in liver. Taken together, the results suggest that $N^{G}$-monomethyl-L-arginine (MMA) and $ N^{G}, N^{G}$-dimethylarginine (DMA) play a role in inhibiting nitric oxide (NO) synthesis in regenerating rat liver because the increase of their contents was synchronized with NOS expression.

• Korean Journal of Veterinary Research
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• v.51 no.2
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• pp.159-164
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• 2011

Alcohol abuse and its medical and social consequences are a major health problem in many areas of the world. Korean red ginseng (KRG) has been traditionally used for the treatment of liver disease. This study was conducted to evaluate the hepatoprotective effects of KRG against hepatotoxicity in Sprague- Dawley rats treated with ethanol (EtOH). Administration of EtOH for 20 days induced significant changes in serum biochemical parameters (aspartate aminotransferase, alanine transaminase, and glucose) accompanied by histological changes in the liver tissue. Treatment with KRG prior to administration of EtOH inhibited the EtOH-induced biochemical and histological changes of the liver. In perfused rat livers, administration of EtOH caused an increase in lactate dehydrogenase (LDH) release into the perfusate and activated the pro-apoptotic Bax protein but inhibited the anti-apoptotic Bcl-2 protein. Pretreatment with KRG prior to administration of EtOH decreased the EtOH-induced LDH release and inhibition of Bcl-2 protein. These results suggest that KRG exerts anti-apoptotic effects and alleviated EtOH-induced liver injury in rats.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.85-96
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• 1993

To investigate the alteration of transferrin receptor (TfR) in the proliferating or transformed liver cells, $^{125}I-transferrin$ binding experiment was carried out in the isolated parenchymal cells (PC) or nonparenchymal cells (NPC) from normal regenerated rat liver after partial hepatectomy and from the liver of 3-methyl-4-dimethyl-aminoazobenzene (3-Me-DAB) treated rat. With the administration of 3-Me-DAB for 8 weeks, the liver tissue showed marked morphologic changes of oval cell proliferation, regenerations of hepatocytes, and atypical proliferations of bile ducts, but these changes were little affected by partial hepatectomy. Transferrin binding values in PC or NPC homogenate from the regenerated liver of normal rat, were increased by 3rd day and diminished to control level at 7th day after partial hepatectomy. With the treatement of 3-Me-DAB for 8 weeks, transferrin binding sites in homogenates were higher than those of normal rat liver and increased by 7th day after partial hepatectomy. Transferrin binding sites (Bmax) in the cell membrane of NPC were higher than those of PC of normal rat liver, but there was no significant difference in Kd values between both groups (5.05, 6.3 nM). In the normal resenerated rat liver, transferrin binding sites in the PC or NPC plasma membrane, were increased by 3rd day and diminished to control level at 7th day after partial hepatectomy. With 3-Me-DAB tratment, transferrin binding sites in both liver NPC and PC plasma membrane were increased about 3 folds, compared to those in each plasma membrane of normal rat liver. And after partial hepatectomy of 3-Me-DAB trated rat, transferrin binding sites were increased by the 3rd day in the NPC plasma membrane but increased by the 7th day in the PC plasma membrane. In the transferrin binding sites of the PC or NPC plasma membrane of 3-Me-DAB treated liver, two kinds of Kd values $(3.1{\sim}4.7\;nM,\;25.4{\sim}54.1\;nM)$ were detected. The present results suggest that 1) TfRs are distributed in the liver PC as well as NPC; 2) Increased TfRs in PC or NPC plasma membrane of normal regenerated liver after partial hepatectomy and 3-Me-DAB treated rat liver, may be due to increased intracellular synthesis; 3) Increased TfRs in normal regenerated liver after partial hepatectomy might be related to the expression of a single type of high affinity site $(Kd,\;3.1{\sim}7.5\;nM)$, but in 3-Me-DAB treated rat liver might be related to the expression of high and low affinity types of receptors $(Kd,\;25.4{\sim}54.1\;nm)$.

• Journal of the Korean Society of Food Science and Nutrition
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• v.22 no.2
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• pp.138-143
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• 1993

In this study the onion juice (2%) in diet fed rats simultaneously ingested lead acetate 100mg/ kg (OP group) showed more increased weight gain than single lead treated rats (P group). The OP group had also improved in the hemoglobin contents and biochemical analyzed values of blood including GPT, blood urea nitrogen and alkaline phosphatase, which were elevated in case of P group rats. The Pb content in the rats liver of OP group was lower than in the rats liver of P group. In the histopathological findings of liver cell OP group rats did not show any signs of liver damage as observed in P group rats that had degenerated hepatocytes, followed sinusoidal dilatation, perivascular hemorrhage and some necrosis of hepatic cells accompanied by increased Kuffer cell bearing dark brown pigment. In conclusion 2% onion juice diet in rat have somewhat antidotic effects on the lead intoxicated rats.

• Journal of Society of Preventive Korean Medicine
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• v.8 no.1
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• pp.115-133
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• 2004

Hasuohwan(何首烏丸) composed of Polygonum multiflorum Thunb and some medical herbs are known as formula of senescence delay effect. The aim of this study is to investigate the effect of Hasuohwan(何首烏丸) on antioxidant enzyme activity such as Thiobarbituric acid reactive substance(TBARS) in rat plasma and liver, Superoxide dismutase(SOD), Glutathione peroxidase(GSH-px), Catalase(CAT) in rat erythrocyte and liver. Rats were sacrificed and TBARS was measured in rat plasma and liver. SOD, GSH-px and CAT were measured in rat erythrocytes and liver. TBARS in plasma concentrations of HSO group was significantly lower than those of control group. RBC and liver GSH-px activities of HSO group were significantly higher than those of control group. According to above results, it is considered that Hasuohwan is effective in inhibiting lipid peroxidation and increasing antioxidative enzyme activities in D-galactose induced aging rat. Therefore, Hsuohwan is considered in effective of senescence delay.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.642-646
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• 2007

It was examined that the effect of fermented traditional wine made by using mycelium of Phellinus linteus (TWPL) on the expression of inflammation-related proteins in rat liver. Levels of aspartate aminotransferase (AST) was significantly increased in the serum of ethanol-treated rats compared to normal. However, the level of AST showed no significant changes in the TWPL-treated rat compared normal. Slight histopathological changes of liver such as cloudy swelling, inflammatory cells infiltration, Kupffer cell reaction were demonstrated in the rats challenged with ethanol compared with normal. Fewer scores of these changes were observed in TWPL-treated rat with recovered glycogen in hepatocytes of whole hepatic lobule. The RT-PCR and Western analysis showed that the expression of inflammatory proteins such as cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor (TNF)-${\alpha}$ were decreased in the TWPL-treated rat compared with ethanol-treated ones. Immunohistochemical analysis showed that the expression of interleukin-lf and TNF-${\alpha}$ tended to decrease in TWPL-treated rat compared with ethanol-treated ones. These results suggest that TWPL may contains some protective agent for alcohol-induced liver injury through a regulating inflammation-related proteins.

• Journal of Nutrition and Health
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• v.27 no.9
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• pp.892-900
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• 1994

A variety of important roles for branched-chain amino acids in metabolic regulation has been suggested. Branched-chain $\alpha$-keto acid dehydrogenase(BCKAD) complex is a rate limiting enzyme in branched-chain amino acid metabolism. The purpose of this study was to examine the effects of exercise on the activity and activity state of branched-chain $\alpha$-keto acid dehydrogenase in rat hert and liver thssues. Forty-eight Sprague-Dawley rats were assigned into three experimental groups : sedentary control, exercised, or exercised-rested. Submaximal exercise(running) for two hours significantly increased basal activity without a change in total activity in both tissues, with a concomitiant increase in activity state of the enzyme complex. At 10 min post-exercise, heart enzyme activity significantly decreased, though not to the control level, while liver enzyme activity remained unchanged. These data suggested that the exercise-induced increase in branched-chain $\alpha$-keto acid decarboxylation in rat tissues may not be the result of enzyme synthesis, but rather is due to increased activity of the BCKAD.

• Journal of the East Asian Society of Dietary Life
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• v.10 no.3
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• pp.200-207
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• 2000

This study was conducted to investigate the nutritional constituents of pine pollen and the effects of pine pollen on rat liver. Using the chemical components analysis method, the constituents of pine pollen are crude protein(13.97%). crude lipid (6.50%), crude ash (3.25%). Detectable in pine pollen are main fatty acids and non-essential amino acids such as glutamic acid and aspartic acid such as oleic and linoleic acid and 18kinds of amino acid including essential amino acids. The effects of pine pollen on rat liver fed with a high fat diet for 6 weeks showed significant decrease in total lipid and triglyceride as compared with the group fed with a fat diet only. Total cholesterol content decreased by 20.33%. No significant difference was found in total protein content of each group. Pine pollen Is efficacious in preventing geriatric diseases (arteriosclerosis, hyper-lipidemia and cardiovascular system-related diseases).