• Advances in Traditional Medicine
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• 제4권2호
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• pp.100-103
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• 2004

The plant Indigofera aspalathoides are used by a large number of tribes in India for the treatment of various hepatic disorder. The methanol extract of Indigofera aspalathoides (MEIA) was evaluated for its effect on carbontetrachloride $(CCl_{4})$ induced liver damage. Biochemical parameters such as serum glutamine oxaloacetate trasaminase (SGOT), serum glutamine pyruvate transaminase (SGPT), serum alkaline phosphatase (ALP), total serum protein (TP), thiobarbituric acid reactive substances (TBRS) and glutathione content of the liver were estimated to assess liver function and metabolism. Biochemical observations suggest that methanol extract of Indigofera aspalathoides (MEIA) significantly restored the liver function and metabolism towards normal condition in $CCl_{4}$-induced hepatic damage.

• 동아시아식생활학회지
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• 제5권3호
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• pp.385-394
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• 1995

Our previous reports on the effect of dietary protein on methanethiol, ethacrynic acid, bromobenzene and carbon tetrachloride metabolism were overall reviewed. The methanethiol, ethacrynicacid and bromobenzene treated rats showed the more severe liver damage in those fed a low protein diet than those fed a standard protein diet. These xenobiotics treated rats showed the lower content of hepatic glutathione and its conjugated enzyme, glutathione S-transferase activities in those fed a low protein diet than those fed a standard protein diet. In case of carbon tetrachloride treated rats, the liver damage was more reduced in rats fed a low protein diet than those fed a standard protein diet. Concomitantly the hepatic cytochrome P-450 content, and its decreasing rate to the control were lower in rats fed a low protein diet than those fed a standard protein diet.

• 생명과학회지
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• 제31권9호
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• pp.796-805
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• 2021

간 소포체(ER) 스트레스는 비알콜성지방간과 인슐린 저항성의 발달에 기여하고, unfolded protein response(UPR)의 구성요소는 지질 대사를 조절한다. 최근 연구에 따르면 ER 스트레스와 비정상적인 세포 지질 대사 사이의 연관성이 보고되었으며, 이 과정에서 지질 대사의 중심 조절자인 sterol regulatory element binding proteins(SREBPs)의 관련성이 확인되었다. 그러나 ER 스트레스 동안 지질 대사를 조절하는 SREBP의 정확한 역할과 비알콜성지방간에 대한 기여는 아직 밝혀지지 않았다. 본 연구에서 SREBP-1c 결핍은 UPR, 염증 및 지방산 산화 조절을 통해 ER 스트레스에 의해 유도된 비알콜성지방간으로부터 생쥐를 보호한다는 것을 보여준다. SREBP-1c는 inositol requiring kinase 1α (IRE1α) 발현을 직접적으로 조절하고 ER 스트레스에 의해 유도된 tumor necrosis factor-α의 활성화를 매개하여 peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1α)의 감소와 그에 따른 지방산 산화의 장애를 유발한다. 그러나, SREBP-1c의 유전적 결핍은 이러한 현상을 보호하여 간 염증과 지방 축적을 완화시킨다. SREBP-1c 결핍이 ER 스트레스에 의해 유도된 염증 신호를 방지하는 메커니즘은 아직 밝혀지지 않았지만, SREBP-1c가 결핍된 Kupffer 세포에서 IRE1α 신호의 변화가 염증 신호에 관여할 수 있을 것으로 생각된다. 본 연구결과는 SREBP-1c가 ER 스트레스에 의해 유도된 비알콜성지방간에서 UPR 및 염증의 조절에 중요한 역할을 함을 시사한다.

• Journal of Applied Biological Chemistry
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• 제44권4호
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• pp.180-184
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• 2001

To investigate the hepatic metabolism of myristicin isolated rat livers were perfused under single-pass conditions with perfusate containing myristicin. In outflow perfusate and bile, 5-allyl-1-methoxy-2,3-dihydroxybenzene (M1), M1-sulfate, and M1-glucuronide conjugates were identified as the metabolites of myristicin. HPLC method with UV detection was applied to investigate the hepatic disposition of the compounds. The concentration of myristicin, M1, and M1-conjugates in the outflow perfusate reached steady-state levels within 20 min after commencing the perfusion of $4.5{\mu}M$ myristicin. At steady-state, the mean (${\pm}S.D.$) extraction ratio of myristicin was $0.49({\pm}0.16)$ and clearance was $13.7({\pm}4.5)ml/min$. M1 accounted for $44.0{\pm}5.3%$ of eliminated myristicin and was recovered as unchanged M1, M1-sulfate, and M1-glucuronide in the bile and outflow perfusate.

• 대한의생명과학회지
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• 제12권2호
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• pp.65-72
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• 2006

Thiazolidinediones (TZDs) are widely used antidiabetic drugs that activate the nuclear peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$, and thereby improve the metabolic abnormalities linking hypertriglyceridemia to diabetes, hyperglycemia, insulin resistance, and cardiovascular disease. To determine whether the $PPAR{\gamma}$ ligand troglitazone regulates lipid metabolism with sexual dimorphism, we examined the effects of troglitazone on circulating lipids, body weight and the expression of hepatic genes responsible for lipid metabolism in both sexes of C57BL/6J mice. Compared to mice fed a low fat control diet, both sexes of mice fed a troglitazone-treated low fat diet for 14 weeks did not exhibit changes in body weight gain, serum total cholesterol, HDL-cholesterol and LDL-cholesterol levels. However, serum triglycerides were significantly reduced in both sexes of mice, although these effects were more pronounced among males. Furthermore, troglitazone regulated the expression of hepatic genes critical for lipid and lipoprotein metabolism, the magnitudes of which were much higher in males compared to females, as evidenced by results for increased acyl-CoA oxidase and decreased apolipoprotein C-III mRMA levels. These results suggest that $PPAR{\gamma}$ activator troglitazone may exert sexually dimorphic control of serum triglycerides in part through the differential activation of $PPAR{\gamma}$ in liver between male and female mice.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.97-97
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• 1997

It was reported that ATP depletion occurs and accelerates cell damage during ischemia and reperfusion. To determine the mechanism of cell damage, the change of energy metabolism in liver was studied during ischemia/reperfusion. The groups were divided into four categories : sham-operated group, ischemia/reperfusion group, and two types of ATP-MgCl$_2$ treatment groups(one was treated during ischemia and the another during reperfusion). Rats were administered intravenously saline or ATP-MgCl$_2$. Rats were anesthetized and blood vessels in the left and median lobes of the liver were occluded. After 60min of ischemia, the clamp at those vessels were removed. After ischemia, one and five hours after reflow, energy metabolites(ATP, ADP, AMP, inosine, adenosine, hypoxanthine, xanthine) in liver were measured with HPLC. To observe mitochondrial function, aterial keton body ratio in blood and mitochondrial glutamate dehydrogenase activity in liver were measured. And lipid peroxidation was measured to evalutate the involvement of free radicals. In this study, ATP and ADP were catabolized to their metabolites(AMP, inosine, adenosine, hypoxanthine, xanthine) during ischemia and they resynthesized ATP and ADP during reperfusion. But total purine base were not restored to level of normal rat. The main source of resynthesizing ATP and ADP was AMP. In both ATP-MgCl$_2$ treated groups, mitochondrial function was protected and lipid peroxidation was significantly reduced. Our findings suggest that ischemia/reperfusion impairs hepatic energy metabolism.

• 대한수의학회지
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• 제38권2호
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• pp.265-272
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• 1998

The effects of mixtures of diazinon(DA;5mg/kg), toxaphene(TOX;40mg/kg) and/or endrin(END; 5mg/kg) on the hepatic mixed-function oxygenase(MFO) system were stuided in ICR mice(18~22g) by oral intubation daily for 7 days. In general, TOX and TOX-containing mixtures were found to induced the metabolism of aminopyrine(22~60%), aniline(42~85%), phenacetin(145~194%) and benzo [a]pyrene(158~210%), and pentobaribtal biotransformation in the 9,000g liver supernatants and to increased the hepatic cytochrome p-450 contents(47~89%). Results of these may be, at least in part, associated with the MFO system. TOX pretreatment increased the aliesterase activity in the serum and liver homogenates and supernatants by 23~145%. The toxicity of TOX and TOX-containing mixtures would be lower than that of diazinon because of TOX-induced increase in the metabolism of diazinon(DA) or diazioxon(DO) and capability of TOX to stimulate the metabolism of diazinon and diazioxon and provide a pool of non-critical enzymes. These results suggest that this information might be helpful in the evaluation of the potential hazard due to occupational and/or environmental exposures to pesticides and their mixtures.

• 대한의생명과학회지
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• 제7권3호
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• pp.99-102
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• 2001

Toluene is mainly metabolized in liver by oxidative pathway. Oxigen free radicals occur through the process of toluene metabolism Therefore it causes tissue and cell min by the oxygen free radicals from the metabolism of toluene. Melatonin acts as a highly efficient free radical scavenger that protects cells from damage by oxygen free radicals. To test this hypothesis, toluene hepatotoxicity was induced by an abdominal injection of toluene. To see if the melatonin protects the rat's liver, melatonin was administrated orally, at the time of each toluene injection. Aspartate aminotransferase(AST), alanin aminotransferase(ALT), latic dehydrogenase(LDH) and alkaline phosphatase(ALP) levels in serum were measured to estimate hepatic function. Malondialdehyde(MDA), which gives an indirect index of oxidative injury was also measured. Hippuric acid is the last metabolic Production of toluene was measured by HPLC. There were significantly higher in AST, ALT, LDH, MDA and hippuric acid in toluene group, but there were no significant difference in melatonin group except ALT and hippuric acid. There was significantly lower in ALP level in toluene group, but there was no significant difference melatonin group, suggesting a significant hepatotoxicity due to oxygen free radicals through the process of toluene metabolism Melatonin treatment significantly protected hepatic function and free radical-mediated injury in the liver against toluene-induced changes. Accordingly, this study shows that melatonin is helpful in protecting liver injury by acute toluene intoxication.

• 대한의생명과학회지
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• 제7권3호
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• pp.111-116
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• 2001

To investigate an effect of aging on the xylene metabolism in liver damaged animals, a study was conducted. 50% carbon tetrachloride ($CCl_4$) in olive oil (0.1 ml/100 g body weight) was intraperitoneally given to 5-week and 12-week rats 12 times every other day and then one dose of 50% xylene in olive oil (0.25 ml/100 g body weight) was intraperitoneally given to the rats, and after 24 hr, the animals were sacrificed. On the basis of the functional findings in rat liver, ie, serum levels of alanine aminotransferase activity, liver protein and malonedialdehyde contents, 5-week rats showed less liver damage than 12-week rats. The increasing rate of urinary methylhippuric acid concentration to the control was significantly higher in 5-week rats than 12-week rats in case of xylene treatment after induction of liver damage. On the other hand, liver damaged 5-week rats showed significant rise of hepatic cytochrome P45O content compared with the liver damaged 12-week rats by the xylene treatment. And increasing rate of hepatic alcohol or aldehyde dehydrogenase activities to each liver damaged animals was higher tendency in 5-week rats than 12-week rats by the xylene treatment. In conclusion, 5-week rat showed greater metabolic rate of xylene than 10-week rats in case of liver injury because 5-week rats led to a slight liver damaged compared with 12-week rats.

• 한국지역사회생활과학회지
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• 제14권3호
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• pp.59-65
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• 2003

This study was carried out to investigate the supplementary effects of the rice germ oil compared with soy bean oil on lipid metabolism of non-insulin dependent diabetic mice. Forty diabetic KK mice were fed two kinds of experimental diets with 20% lipid from soy bean oil as a control(CO) and rice germ oil(RG) for 8 weeks, respectively. Diet intake, body weight, organs weights and lipids levels of serum, liver and feces were measured. There was no significant difference in food and water intake, body weight gain and organs weights between experimental groups. But the concentrations of serum total cholesterol and LDL-cholesterol were lower in RG group than in CO group. The hepatic total lipid and total cholesterol levels of RG group were significantly lower than those of CO group. The contents of total lipid, triglyceride and total cholesterol excreted in feces of RG group were higher than those of CO group. These results suggested that rice germ oil can reduce serum total cholesterol and LDL-cholesterol and hepatic total lipid concentration of non-insulin dependent diabetic mice compared with soybean oil due to increasing fecal lipid excretion. But we need to investigate the hypolipidemic effect of this oil by supplementary level and period.