• Archives of Pharmacal Research
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• v.28 no.12
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• pp.1386-1391
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• 2005

This study examined the role of Kupffer cells in altering the hepatic secretory and microsomal function during ischemia and reperfusion (ls/Rp). Rats were subjected to 60 min of hepatic ischemia, followed by 1 and 5 h of reperfusion. Gadolinium chloride ($GdCl_{3}$, 7.5 mg/kg body weight, intravenously) was used to inactivate the Kupffer cells 1 day prior to ischemia. Is/Rp markedly increased the serum aminotransferase level and the extent of lipid peroxidation. $GdCl_{3}$ significantly attenuated these increases. Is/Rp markedly decreased the bile. flow and cholate output, and $GdCl_{3}$ restored their secretion. The cytochrome P450 content was decreased by Is/Rp. However, these decreases were not prevented by $GdCl_{3}$. The aminopyrine N-demethylase activity was decreased by Is/Rp, while the aniline p-hydroxylase activity was increased. $GdCl_{3}$ prevented the increase in the aniline p-hydroxylase activity. Overall, Is/Rp diminishes the hepatic secretory and microsomal drug-metabolizing functions, and Kupffer cells are involved in this hepatobiliary dysfunction.

• The Korean Journal of Nuclear Medicine
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• v.3 no.1
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• pp.1-12
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• 1969

Liver functions in diffuse parenchymal liver disease such as cirrhosis of the liver depend largely on the effective hepatic blood flow rather than on the individual cell functions. Clinical methods of measuring the hepatic blood flow were developed recently by the application of colloidal disappearance rate. In order to correlate the radiogold disappearance rate to conventional biochemical liver function tests, 21 normal subjects and 80 cases of cirrhosis of the liver were studied with both methods. The results are summarized as following: 1. The validity of external counting method to measure the blood disappearance rate of colloidal radiogold was confirmed by in vitro counting of the serial blood samples. 2. The blood disappearance rate of collidal radiogold was essentially the same. as the liver uptake rate of colloidal radiogold in normal and cirrhotic subjects with various degrees of functional disturbance. And it seemed there was no serious extrahepatic removal of the colloidal radiogold. 3. The disappearance rate of colloidal radiogold was not significantly changed by the posture change, but was enhanced by ingestion of 500 ml of water. 4. The disappearance rate of colloidal radiogold was not influenced by single dose of Telepaque, while BSP retention was increased after Telepaque. 5. The mean disappearance half time of colloidal radiogold in normal subjects was $2.49{\pm}0.391$(S.D.) minutes. The mean normal disappearance rate constant (K value) was $0.285{\pm}0.0428$(S.D.)/minute. 6. The colloidal radiogold disappearance half time was abnormally prolonged (over 3.2 min.) in $87.7{\pm}3.68$(S.D.) % of cirrhotic subjects. 7. In patients of liver cirrhosis the blood disappearance rate of colloidal radiogold correlated well to serum albumin and globulin levels and BSP retention which were considered to reflect functions of hepatic parenchymal cells. There was, however, no correlation between colloidal disappearance rate and thymol turbidity test, serum glutamic pyruvic transaminase, and serm alkaline phosphatase activities. The latters were considered to be associated with the activity of liver disease.

• Journal of Microbiology and Biotechnology
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• v.12 no.5
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• pp.735-739
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• 2002

Large quantities of porcine hepatocyte aggregates with various degrees of aggregation (DA) could be obtained by controlling the suspension periods (0,9,24, and 48 h), and by entrapping the hepatocyte aggregates in model materials of encapsulation such as Ca-alginate and type-I collagen gels. The effects of DA on liver-specific functions of hepatocytes were evaluated in order to obtain optimum DA for the cell source of bioartificial liver (BAL) systems. Irregular rugged aggregates (size $75 \pm 28$ $\mu\textrm{m}$) farmed by 24 h of suspension culturing showed peak viability and hepatic functions such as ammonia removal and albumin secretion in the two types of entrapment systems, thus offering themselves as a stable cell source of a BAL system for hepatic functions and scale-up.

• Journal of Nutrition and Health
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• v.31 no.2
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• pp.126-134
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• 1998

Our previous study demonstrated that dietary taurine or glycine supplementation significantly lowered plasma and hepatic cholesterol and triglyceride concentrations in rats fed a cholesterol-free diet. In the present study, the effect of long term dietary taurine or glycine supplementation, for the purpose of preventing and/or treating of hyperlipidemia and other known biological functions, on plasma and hepatic free amino acid concentrations and profiles were evaluated in rats. Three groups of male rats(110-130g) were fed a control diet(CD), taurine-supplemented diets(TSD ; CD+ 1.5% taurine) or glycine-supplemented diet(GSD ; CD+1.5% glycine) for 5 weeks. Plasma and hepatic free amino acid concentrations were determined by an automated amino acid analyzer based on ion-exchange chormatography. The feeding of TSD for 5 weeks yielded a 444% higher plasma taurine concentration , and the feeding GSD for the same period resulted in a 143% higher plasma glycine level in rats compared to those fed DB. Hepatic taurine concentration was significantly higher in rats fed TSD(145% increase) compared to the control rats. However, hepatic glycine concentration was not influenced by dietary glycine supplementation , which implies that the massive dose of glycine entering the body was more rapidly metabolized or excreted than taurein. Dietary taurine or glycine supplementation resulted in similar changes in plasma free amino acid concentrations, except in levels of taurine and glycine. Plasma levels of histidine, lysine, phenylalanine , alanine, proline, hydroxypoline, $\alpha$-aminogutyric acid, cystathionine and ethanolamine were significantly higher in rats fed TSD or GSD than those fed GD. Glycine supplementation did not change hepatic free amino acid concentrations as compared to CD. Concentrations of most hepatic free amino acids were not influenced by dietary taurine supplementation with the exception of significantly higher levels of asparate and tyrosine(56-63% increase) and lower levels of histidine and glutamate(33-34% decrease) compared to the control rats. These results suggest long-term dietary taurine or glycine supplementation resulted in increases in most plasma free amino acid levels, but did not cause a characteristic change in plasma aminogram pattern compared to rats fed CD.

• Korean Journal of Head & Neck Oncology
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• v.16 no.2
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• pp.206-211
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• 2000

Objectives: Any uptake of I-131 after total thyroidectomy means the remant thyroid tissue or distant metastasis of the thyroid cancer. However diffuse hepatic uptake of I-131 without abnormal uptake was showen in many cases on I-131 whole body scan. The aim of this study was to classify the liver uptake after I-131 scan and to evaluate the analysis of this finding. Materials and Methods: Between 1982 and 1998, 104 patients(l4 males, 90 females) with normal liver function underwent I-131 scan after total thyroidectomy. Prospectively we reviewed the films of the whole body scan and analysed the correlations between results of radioiodine uptake, pathologic diagnosis, prognostic factors, lymphatic metastasis, and thyroid function test. Result: Diffuse hepatic uptake was found in 44 of 104(42%) patients. 10 of 39(26%) patients on I-131 100mCi, and 34 of 63(54%) on I-131 150mCi showed hepatic uptake. 52 of 104(50%) patients was locally invasive thyroid cancer. The rate of the hepatic uptake was no significant differences with the thyroid hormone levels(T3, Free T4) and thyroglobulin between uptake group and non-uptake group. Conclusion: The rate of I-131 uptake was high in high-dose radioiodine treatment group. However, we can not find any correlation among the thyroid functions, the extent of metastasis or the extent of local invasion. We need further study to find out the causes of the hepatic uptake of I-131 after total thyroidectomy, besides liver metabolism of I-131 attached thyroid hormones.

• Archives of Pharmacal Research
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• v.18 no.3
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• pp.189-194
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• 1995

The focus of this study was to investigate the influences of enzymatic scavengers of active oxygen metabolites and phospholipase $A_2$ inhibitor on hepatic secretory and microsomal function during hepatic ischemia/reperfusion. Rats were pretreated with free radical scavengers such as superoxide dismutase (SOD), catalase, deferoxamine and phospholipase $A_2$ inhibitor such as quinacrine and then subjected to 60 min. no-flow hepatic ischemia in vivo. After 1, 5 hr of reperfusion, bile was collected, blood was obtained from the abdominal aorta, and liver microsomes were isolated. Serum aminotransferase (ALT) level was increased at 1 hr and peaked at 5 hr. The increase in ALT was significantly attenuated by SOD plus catalase, deferoxamine and quinacrine especially at 5 hr of reperfusion. The wet weight-to-dry weight ratio of the liver was significantly increased by ischemia/reperfusion. SOD and catalase treatment minimized the increase in this ratio. Hepatic lipid peroxidiltion was elevated by ischemia/reperfusion, and this elevation was inhibited by free radical scavengers and quina crine. Bile flow and cholate output, but not bilirubin output, were markedly decreased by ischemia/reperfusion and quinacrine restored the secretion. Cytochrome $P_{450}$ content was decreased by ischemia/reperfusion and restored by free radical scavengers and quinacrine to the level of that of the sham operated group. Aminopyrine N-demethylase activity was decreased and aniline p-hydroxylase was increased by ischemia/reperfusion. The changes in the activities of the two enzymes were prevented by free radical scavengers and quinacrine. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory functions as well as microsomal drug metabolizing systems by increasing lipid peroxidation, and in addition to free radicals, other factors such as phospholipase $A_2$ are involved in pathogenes of hepatic dysfunction after ischemia/reperfusion.

• Biomolecules & Therapeutics
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• v.3 no.4
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• pp.304-310
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• 1995

This study was done to investigate the effect of vitamin C on hepatic biliary and microsomal function during ischemia and reperfusion. Rats were treated with vitamin C(20, 100, 400, 1600 mg/kg) or with vehicle(saline) and then subjected to 60 min no-flow hepatic ischemia in vivo. Control animals were time-matched sham ischemic animals. After 1 or 5 hr of reperfusion, bile was collected, blood was obtained from the abdominal aorta, and liver microsomes were isolated. In vehicle-treated ischemic rats, serum ALT and AST levels peaked at 5 hr and were significantly attenuated by vitamin C 20 mg/kg and 100 mg/kg treatment. Similarly, hepatic wet weight-to-dry weight ratio was decreased in the vehicle-treated ischemic group. Vitamin C 20 mg/kg and 100 mg/kg treatment minimized the increase in this ratio. Lipid peroxidation was elevated in vehicle-treated ischemic group, but this elevation was also inhibited by vitamin C 20 mg/kg and 100 mg/kg treatment. Bile flow and cholate output, but not bilirubin output, were markedly decreased by ischemia/reperfuzion. Vitamin C 20 mg/kg and 100mg/kg treatment restored the secretion but vitamin C 1600 mg/kg reduced the cholate output. Cytochrome P-450 content was decreased by ischemia/reperfusion and restored by vitamin C 20 mg/kg and 100 mg/kg treatment to the level of sham operated group but decreased by vitamin C 1600 mg/kg. Aminopyrine N-demethylase activity was decreased and aniline p-hydroxylase activity was increased by ischemia/reperfusion. The changes in the activities of aminopyrine were prevented by vitamin C 20 mg/kg and 100 mg/kg treatment, but not by 400 mg/kg and 1600 mg/kg treatment. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory functions as well as microsomal drug metabolizing systems, small doses(20, 100 mg/kg) of vitamin C significantly ameliorates and large doses(400, 1600 mg/kg) of vitamin C aggravated these ischemia/reperfusion-induced changes.

• Journal of the East Asian Society of Dietary Life
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• v.23 no.1
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• pp.44-52
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• 2013

This study investigated hepatic functional improvement and anti-fibrotic effects of water extracts of black tea. Male Sprague-Dawley rats were divided into four groups (normal, control, and two experimental subgroups: Ba, Bb) and observed for 3 weeks. Liver fibrosis in rats developed from carbon tetrachloride ($CCl_4$) administration, except for the normal group. Except for the normal and control group, the two experimental subgroups were fed water extracts of black tea. The food efficiency ratio significantly increased in the experimental group compared to the control group. The experimental group had a significantly lower liver weight compared to the control group. The ratio of liver weight to body weight was significantly lower in the experimental group than the control group. The levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, and low-density lipoprotein-cholesterol in serum significantly decreased in the experimental group compared to the control group. The values of hydroxyproline and malondialdehyde in liver were even lower in the experimental group than the control group. In observations on liver histology, weaker inflammation and fibrosis were observed in the experimental group compared to the control group. In conclusion, water extracts of black tea help hepatic cells keep their functions, restraining and protecting the liver from impairments caused by $CCl_4$ administration, and can be effective as anti-fibrotic agents.

• Proceedings of the Ginseng society Conference
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• 1987.06a
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• pp.47-58
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• 1987

Ethanol exerts different effects on hepatic cellular metabolism, depending mainly on the duration of its intake. In the presence of ethanol following an acute load, a number of hepatic functions are inhibited, including lipid oxidation and microsomal drug metabolism. In its early stages, chronic ethanol consumption produces adaptive metabolic changes in the endoplasmic reticulum which result in increased metabolism of ethanol and drugs and accelerated lipoprotein production. Prolongation of ethanol intake may result in injurious hepatic lesions such as alcoholic hepatitis and cirrhosis A number of such metabolic effects of ethanol are directly linked to the two major products of its oxidation; hydrogen and acetaldehyde. The excess hydrogen from ethanol unbalances the liver cell's chemistry. In the presence of excess hydrogen ions the process is turned in a different direction. In this study, it was attempted to observe the effect of ginseng saponins on alcohol Oehydrogenase(ADH), aldehyde dehydrogenase(ALDH) and microsomal ethanol oxidizing system(MEOS) in vivo as well as in vitro. Furthermore, the effect of ginseng saponin on the hydrogen balance in the liver and the hepatic cellular distribution of (1-14C) ethanol, its incorporation into acetaldehyde and lipids was also investigated. It seemed that ginseng saponin stimulated the above enzymes and other related enzymes in ethanol metabolism, resulting in a rapid removal of acetaldehyde and excess hydrogen from the animal body,

• Proceedings of the KSME Conference
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• 2008.11a
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• pp.1419-1426
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• 2008

Fulminant hepatic failure is a clinical syndrome associated with a high mortality rate. Orthotopic liver transplantation is the only clinically proven effective treatment for patients with end-stage liver disease who do not respond to medical management. A major limitation of this treatment modality is the scarcity of donor organs available, resulting in patients dying while waiting for a donor liver. An extracorporeal bioartificial liver (BAL) device containing viable hepatocytes has the potential to provide temporary hepatic support to liver failure patients, serving as a bridge to transplantation while awaiting a suitable donor. In some patients, providing temporary hepatic support may be sufficient to allow adequate regeneration of the host liver, thereby eliminating the need for a liver transplant. Although the BAL device is a promising technology for the treatment of liver failure, there are several technical challenges that must be overcome in order to develop systems with sufficient processing capacity and of manageable size. In this overview, the authors describe the critical issues involved in developing a BAL device. They also discuss their experiences in hepatocyte culture optimization within the context of a microchannel flat-plate BAL device.