• Journal of Ginseng Research
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• 제14권2호
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• pp.187-190
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• 1990

Maltol(2-methyl-3-hydroxy-r-pyrone), a component known to be present in Korean Ginseng root showed an antioxidant action but its potency as an antioxidant was low: about 1150th that of other antioxidants such as pphenylenediamine, BHA and BHT. However, maltol was able to protect the oxidation damages in biological systems such as adriamycin-induced membrane damage in isolated cardiomyocytes, paraquat-induced toxicities in isolated hepatocytes and reperfusion injury in isolated hearts. The antioxidant action of maltol was also shown to be effective in vivo. The antioxidant action of this compound was probably due to the removal of hydroxyl radicals. In view of the roles of oxygen radical in various pathological proceises, Korean Ginseng root which contains several antioxidants including maltol is expected to have beneficial effects on the oxygen radical-involved processes.

• Toxicological Research
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• 제7권2호
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• pp.183-189
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• 1991

Since streptozotocin has been known to be chemically stable only under acidic condition(pH 4), the spontaneous degradation and cellular uptake of streprozotocin in neutral incubation medium was determined by chemical assay. Streptozotocin levels in both phosphate buffered saline (pH 7.4) and Krebs-Henseleit buffer (pH 7.4) decreased with a half life of about 2 hours. The presence of erythrocytes or pepatocytes under the same buffers did not affect the streptozotocin degradation rate at all. However, streptozotocin levels in plasma isolated from rats decreased rapidly compared to those in neutral buffers.

• Journal of Pharmaceutical Investigation
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• 제27권1호
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• pp.1-10
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• 1997

For the purpose of improving the chemotherapeutic index of acyclovir(ACV), it was conjugated with asialofetuin(AF), which has been reported to enter into hepatocytes. When $[H^3]$ acyclovir in itself or its conjugate were administered to rats, the latter was taken up more selectively by the liver than any other tissues. The stability of ACVMP-AF conjugate in phosphate buffer (pH 5.0) and rat liver homogenate showed a pseudo-first order profile. ACVMP-AF, however, was relatively stable in pH7.4 phosphate buffer and rat plasma. The conjugate was added to the isolated rat hepatocyte and cellular uptake was monitored by scintillation counting for up to 6 hours at $37^{\circ}C$. Hepatocytes incubated with the conjugate exhibited radioactivities significantly enhanced over control levels dose-dependently, i.e., a 3-40 fold increase in radioactivities was observed over controls at the conjugate concentrations of $0.1-10\;{\mu}g/ml$. The AUQ in the liver, kidney, spleen, intestine and lung was higher in treatment with ACVMP-AF than that in treatment with ACV. In treatment with ACVMP-AF, the weighted-average overall drug targeting efficiency(Te) for the liver was higher than in treatment with ACV(57.00 vs 13.31 %), and the weighted-average tissue exposure(Re) was 5.03 for the liver. These results indicated that ACVMP-AF conjugate was rapidly taken up by hepatocytes and could be an efficient and selective hepatic targeting system.

• BMB Reports
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• 제40권6호
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• pp.1039-1049
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• 2007

Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.

• Archives of Plastic Surgery
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• 제39권6호
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• pp.593-599
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• 2012

Background This study aimed to investigate the possibility of isolating mesenchymal stem cells (MSCs) from human thigh adipose tissue and the ability of human thigh adipose stem cells (HTASCs) to differentiate into hepatocytes. Methods The adipose-derived stem cells (ADSCs) were isolated from thigh adipose tissue. Growth factors, cytokines, and hormones were added to the collagen coated dishes to induce the undifferentiated HTASCs to differentiate into hepatocyte-like cells. To confirm the experimental results, the expression of hepatocyte-specific markers on undifferentiated and differentiated HTASCs was analyzed using reverse transcription polymerase chain reaction and immunocytochemical staining. Differentiation efficiency was evaluated using functional tests such as periodic acid schiff (PAS) staining and detection of the albumin secretion level using enzyme-linked immunosorbent assay (ELISA). Results The majority of the undifferentiated HTASCs were changed into a more polygonal shape showing tight interactions between the cells. The differentiated HTASCs up-regulated mRNA of hepatocyte markers. Immunocytochemical analysis showed that they were intensely stained with anti-albumin antibody compared with undifferentiated HTASCs. PAS staining showed that HTASCs submitted to the hepatocyte differentiation protocol were able to more specifically store glycogen than undifferentiated HTASCs, displaying a purple color in the cytoplasm of the differentiated HTASCs. ELISA analyses showed that differentiated HTASCs could secrete albumin, which is one of the hepatocyte markers. Conclusions MSCs were islolated from human thigh adipose tissue differentiate to heapatocytes. The source of ADSCs is not only abundant abdominal adipose tissue, but also thigh adipose tissue for cell therapy in liver regeneration and tissue regeneration.

• Genomics & Informatics
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• 제8권1호
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• pp.41-49
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• 2010

Statins are competitive inhibitors of hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and used most frequently to reduce plasma cholesterol levels and to decrease cardiovascular events. However, statins also have been reported to have undesirable side effects such as myotoxicity and hepatotoxicity associated with their intrinsic efficacy mechanisms. Clinical studies recurrently reported that statin therapy elevated the level of liver enzymes such as ALT and AST in patients suggesting possible liver toxicity due to statins. This observation has been drawn great attention since statins are the most prescribed drugs and statin-therapy was extended to a larger number of high-risk patients. Here we employed rat primary hepatocytes and microarray technique to understand underlying mechanism responsible for statin-induced liver toxicity on cell level. We isolated genes whose expressions were commonly modulated by statin treatments and examined their biological functions. It is of interest that those genes have function related to response to stress in particular immunity and defense in cells. Our study provided the basic information on cellular mechanism of statin-induced cytotoxicity and may serve for finding indicator genes of statin -induced toxicity in rat primary hepatocytes.

• Asian-Australasian Journal of Animal Sciences
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• 제13권9호
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• pp.1285-1289
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• 2000

This study investigated the lipogenesis capacity of hepatocytes and lipolysis rate of adipocytes of broilers as affected by different fatty acids (trial one) and different linoleic acid (C18:2) levels (trial two). Twenty 6-wk old broilers were used; their hepatocytes and adipocytes were isolated for the in vitro study. In trial one, four treatments were tested. The control group in which no fatty acid was added, and the test groups to which were added $300{\mu}M$ of C16:0, C18:1 and C18:2, respectively. For trial two, different levels (0, $300{\mu}M$ and 1 mM) of C18:2 combined to fatty acid-free bovine serum albumin (BSA) were added to the medium. According to results of trial one, added fatty acids significantly reduced the incorporation by hepatocytes of [U,$^{14}C$]glucose into total lipid (p<0.05); the lipogenesis capacity in C18:2 group was the lowest. Although a similar pattern was found with [l,$^{14}C$]acetate, the groups only slightly differed in terms of lipogenesis capacity (p=0.11). In addition, the C18:2 group had a significantly (p<0.05) greater lipolysis rate than the C16:0 and control groups. Results of trial two indicated that C18:2 significantly (p<0.05) reduced lipogenesis capacity both for [U,$^{14}C$]glucose and [l,$^{14}C$]acetate, and markedly stimulated the lipolysis rate (p<0.05), displaying a dose response. Results presented herein demonstrate that C18:2 can reduce lipogenesis capacity and stimulate the lipolysis rate in broilers.

• Biotechnology and Bioprocess Engineering:BBE
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• 제8권1호
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• pp.41-46
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• 2003

Difficulties associated with bioartificial liver (BAL) preservation limit not only the commercialization of BAL, but also its clinical trials. In this study, the possibility of cold preservation of BAL cartridges containing porcine hepatocytes was examined at 4$^{\circ}C$. In an in vitro perfusion culture System, BAL cartridges maintained cytochrome P450 metabolic function for at least 50 days. However, all BAL cartridges completely lost their ammonia eliminating ability when stored at 4$^{\circ}C$. We a1so studied the effect of cell density on the maintenance of BAL liver function In a highly differentiated and healthy state. As expected, BALs containing a larger number of hepatocytes demonstrated higher metabolic functions. When metabolic functions were compared per gram of hepatotytes, no large differences were observed between devices containing different densities of hepatocytes. Decreased cell density did not Successfully prolong BAL function. The viability and function of isolated hepatotytes highly depend on the culture conditions, such as cell density, substrata, culture media, and additives to the culture media. Perfusion culture of BAL cartridges at 4$^{\circ}C$ gave a promosing result with respect to the maintenance of P450 activity. However, as indicated by the rapid loss of ammonia metabolic activity, many factors still remain to be optimized for preservation of BAL keeping high metabolic functions for a longer time.

• Applied Microscopy
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• 제21권1호
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• pp.63-76
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• 1991

Butylated hrdroxyanisole(BHA), a widely used food additive phenolic antioxidant, is known to inhibit cancer formations inducible with a wide variety of chemical carcinogens including aflatoxin $B_1(AFB_1)$. Thus, in the present study morphological characteristics underlying the hepatoprotective effects of BHA against $AFB_1$ inducible ultrastructural changes of hepatocytes have been examined. The obtained results are as follows : 1 . Livers obtained from rats treated with $AFB_1$ in vivo have been examined with transmission electron microscope. Among the many hepatocellular structural aberrations induced by $AFB_1$ treatment, the nuclear chromatins were found to be distributed irregularly('cap formation') and the nuclear membrane was found to be partially segregated. Furthermore, there were many lipid droplets, hyperplasia of smooth endoplasmic reticulum, dialated rough endoplasmic reticulum and, lysosomes arrested at various stages of its development. 2. Also, when $AFB_1$ was given in vitro to hepatocytes which have been isolated from untreated normal rats and examined under scanning electron microscope, there were much 'blobbing' phenomena resulting from cytoskeletal disturbances. 3. However, in the liver obtained from rats pretreated with BHA and then give the $AFB_1$, the observed morphological aberrations were in much reduced extent. Similarly, the BHA-hepatocytes had much decreased severity in the $AFB_1$ inducible blob formations.

• 한국식품영양과학회지
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• 제26권6호
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• pp.1173-1180
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• 1997

Hepatotoxicity of caffeine and acetaminophen was investigated in this study. Special attention was paid to the effect of vitamins on the reduction of hepatotoxicity caused by the chemicals. Rat hepaocytes isolated by two-step perfusion method were cultured in two differents methods-suspension, monolayer cultures-, and exposed to caffeine and/or acetaminophen for 24hrs. Caffeine or acetaminophen exhibited no significant hepatotoxicity in terms of intracellular glutathione(GSH) level and lipid peroxidation(MDA), but GSH level was significantly decreased after administrated acetaminophen, and the toxicity caused by the chemicals showed a dose-dependent manner. The synergistic effect of caffeine and acetaminophen was observed when both caffeine and acetaminophen were supplemented to culture medium. At the concentration 1mM, caffeine enhanced the intracellular GSH depletion and MDA formation by 63% and 64%, respectively, compared to single supplementation of 10mM acetaminophen in culture medium. This hepatotoxicity induced membrane integrity loss was observed by lightmicroscope on the simultaneous administration of caffeine and acetaminophen in monolayer cultured hepatocytes. Co-supplementation of vitamins with caffeine/acetaminophen to culture medium results in the protection of hepatocytes from hepatotoxic attach by caffeine/acetaminophen. Especially, vitamin E was superior to vitamin C and $\beta$-carotene from the standpoints of GSH depletion and MDA formation. From this results, it has been speculated that vitamin E may play a role of antioxidant scavenging radicals produced from acetaminophen. Taken all together, in vitro culture system like monolayer culture of hepatocytes may be a useful tool for the evaluation of hepatotoxicity or protection ability of food ingredients.