• Fisheries and Aquatic Sciences
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• v.14 no.2
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• pp.79-88
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• 2011

The sea tangle, Laminaria japonica has long been used in Korea as a folk remedy to promote health. Gamma-amino butyric acid-enriched (5.56% of dry weight) sea tangle was obtained by fermentation with Lactobacillus brevis BJ-20 (FLJ). A suppressive effect of FLJ on carbon tetrachloride-induced hepatotoxicity has been shown previously. Alcohol administration to Sprague-Dawley rats leads to hepatotoxicity, as demonstrated by heightened levels of hepatic marker enzymes as well as increases in both the number and volume of lipid droplets as fatty liver progresses. However, FLJ attenuated alcohol-induced hepatotoxicity and the accumulation of lipid droplets following ethanol administration. Additionally, FLJ increased the activities and transcript levels of major alcoholmetabolizing enzymes, such as alcohol dehydrogenase and aldehyde dehydrogenase, and reduced blood concentrations of alcohol and acetaldehyde. These data suggest that FLJ protects against alcohol-induced hepatotoxicity and that FLJ could be used as an ingredient in functional foods to ameliorate the effects of excessive alcohol consumption.

• YAKHAK HOEJI
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• v.42 no.6
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• pp.598-606
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• 1998

The liver expresses a considerable amount of nitric oxide (NO) upon induction with cytokines or/and endotoxin. The NO synthesized by inducible NO synthase (NOS) of the liver see ms to play a role in various hepatic physiological processes. Here we investigate the effects of NO on acetaminophen (AA)-induced liver injury. The treatment of S-nitros-N-acetyl penicillamine (SNAP, exogenous NO donor) at the dose of 0.1mM decreased AA-induced hepatotoxicity suggesting the possibility of NO to play a role in protection from the hepatotoxicity induced by AA. On the other hand, the excessive NO produced by NO donor (SNAP: 0.5, 2.5, 6.25mM) has been shown to cause a concentration dependent hepatotoxicity, and such damages was decreased by Superoxide and increased by superoxide dismutase, indicating that the hepatotoxicity induced by excessive NO depends on balancing between NO and superoxide. Taken together, the results indicate that NO has biphasic effects on hepatotoxicity.

• BMB Reports
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• v.39 no.6
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• pp.656-661
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• 2006

Cisplatin (CDDP) is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because silymrin has been used to treat liver disorders, the protective effect of silymarin on CDDP -induced hepatotoxicity was evaluated in rats. Hepatotoxicity was determined by changes in serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST], nitric oxide [NO] levels, albumin and calcium levels, and superoxide dismutase [SOD], glutathione peroxidase [GSHPx] activities, glutathione content, malondialdehyde [MDA] and nitric oxide [NO] levels in liver tissue of rats. Male albino rats were divided into four groups, 10 rats in each. In the control group, rats were injected i.p. with 0.2 ml of propylene glycol in saline 75/25 (v/v) for 5 consecutive days [Silymarin was dissolved in 0.2 ml of propylene glycol in saline 75/25 v/v]. The second group were injected with CDDP (7.5 mg /kg, I.P.), whereas animals in the third group were i.p. injected with silymarin at a dose of 100 mg/kg/day for 5 consecutive days. The Fourth group received a daily i.p. injection of silymarin (100 mg/kg/day for 5 days) 1 hr before a single i.p. injection of CDDP (7.5 mg/kg). CDDP hepatotoxicity was manifested biochemically by an increase in serum ALT and AST, elevation of MDA and NO in liver tissues as well as a decrease in GSH and the activities of antioxidant enzymes, including SOD, GSHPx in liver tissues. In addition, marked decrease in serum NO, albumin and calcium levels were observed. Serum ALT, AST, liver NO level, MDA was found to decreased in the combination group in comparison with the CDDP group. The activities of SOD, GSHPx, GSH and serum NO were lower in CDDP group than both the control and CDDP pretreated with silymarin groups. The results obtained suggested that silymarin significantly attenuated the hepatotoxicity as an indirect target of CDDP in an animal model of CDDP-induced nephrotoxicity.

• Journal of Haehwa Medicine
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• v.9 no.2
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• pp.111-121
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• 2001

In order to evaluate the protective effect of Kamicheungkantang(KCKT) on hepatic damage induced by $CCl_4$, the study was done. The blood chemistry and histological study were done following oral administration with materials. The results were obtained as follows. 1. KCKT extracts didn't show cytotoxicity against BALB/C mouse lung fibroblast cell. 2. In the hepatotoxicity with $CCl_4$, serum alanine aminotransferase(ALT) was significantly decreased in KCKT treated group as compared with control group. 3. In the hepatotoxicity with $CCl_4$, serum aspartate aminotransferase (AST) was significantly decreased in KCKT treated group as compared with control group. 4. In the hepatotoxicity with $CCl_4$, serum alkaline phosphatase(ALP) was significantly decreased in KCKT treated group as compared with control group. 5. In the hepatotoxicity with $CCl_4$, serum lactate dehydrogenase(LDH> was insignificantly decreased in KCKT but insignificantly as compared with control group. 6. In the hepatotoxicity with $CCl_4$, serum cholestorol was significantly decreased in KCKT treated group as compared with control group. 7. In the hepatotoxicity with $CCl_4$, serum triglyceride was insignificantly decreased in KCKT treated groups as compared with data of control. 8. In the hepatotoxicity with $CCl_4$, serum total bilirubin, direct bilirubin, ${\gamma}$-GTP were not changed in KCKT treated groups as compared with data of control. 9. In histopathological changes, fatty changes, vacuole, nucleotic changes and fibrosis were observed in control group and degree of changes was increased over time. Whereas no differences were observed in KCKT treated group These results suggested that KCKT extracts might be usefully applied for treatment of hapatic disease and also it was necessary to do more studies about its mechanisms.

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.6
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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.

• Journal of The Korean Society of Clinical Toxicology
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• v.16 no.2
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• pp.149-156
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• 2018

Purpose: The purpose of this study was to determine whether hepatotoxicity could be predicted early using biochemical markers in patients with acetaminophen (AAP) poisoning and to assess the usefulness of predictive factors for acute liver injury or hepatotoxicity. Methods: This study was a retrospective observational study involving a medical records review. The participants were patients who were admitted to the emergency department (ED) with AAP overdose at two hospitals over a 10-year period. Demographic data, age, time from ingestion to visit, initial AAP level, initial hepatic aminotransferases, and initial prothrombin time were recorded. Acute liver injury was defined as a peak serum ALT >50 U/L or double the admission value, and hepatotoxicity was defined as a peak ALT >1,000 U/L. Receiver operating characteristic curve analyses were performed to compare the prognostic performance among variables. Results: A total of 97 patients were admitted to the ED with AAP overdose, of whom 26 had acute liver injury and 6 had hepatotoxicity. Acute liver injury was associated with the time interval after taking the drug, and hepatotoxicity was associated with the initial PT and the ALT level. The scoring system proposed by the authors has a significant ability to predict both acute liver injury and hepatotoxicity. Conclusion: To predict the prognosis of AAP poisoning patients, the time interval after taking AAP was important, and initial prothrombin time and ALT level were useful tests. Also a scoring system combining variables may be useful.

• Environmental Analysis Health and Toxicology
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• v.17 no.2
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• pp.175-185
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• 2002

To investigate effects of A. gmelini on the 14-day CCl$_4$induced hepatotoxicity, extracts were prepared in 3 ml saline at the dose of 50, 500, 5,000 mg/kg b.w. to administer orally everyday and same concentration (1 : 9, CCl$_4$: olive oil v/v) of CCl$_4$administered intraperitoneally with 2.5 ml/kg b.w. On the 7th day, hemanalysis showed following recovery values; AST 9.9∼64.6%, ALT 36.9∼71.9%, ALP 75.3∼93.7％, BUN 53.8∼59.7%, TBIL 60.4∼100.0< ％, TCHO 77.7∼100.0< ％, and TG 60.4∼100.0< ％. Even if, 14-day CCl$_4$induced hepatotoxicity recovery was found to depend on doses of extract, and recovery values of each treatment were AST 13.8∼56.4％, ALT 15.7∼68.0％, ALP 53.4∼84.4％, BUN 76.9∼100.0< ％, TBIL 60.4 ∼ 100.0< %, TCHO 82.6∼99.3< ％, and TG 56.7∼99.7%. By histological examination of liver, hydropic degeneration, fatty change, lipid accumulation and necrosis were also recovered.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.5
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• pp.919-926
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• 2011

The purpose of this study is to inspect trends of the paper of Korean medical treatment on Carbon Tetrachloride-induced Hepatotoxicity and try to establish the future direction for development of Korean herbal medicine. We reviewed 79 papers which had been published from 1981 to 2010 in journals published in Korea. According to these studies, Carbon Tetrachloride-induced hepato-celluar degeneration and necrosis induced to increase in serum aspartate amintransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP), ${\gamma}$-Glutamyl transferase (${\gamma}$-GTP), lactate dehydrogenase (LDH), bilirubin, blood urea nitrogen (BUN) and albumin levels. In biochemical analyses, antioxidant enzymes such as superoxide dismutase (SOD), Glutathione S-transferase (GST) and catalase in hepatic tissue were remarkably incresed by Carbon Tetrachloride treatment. We found that some of the herbal extracts have a protective effect against Carbon Tetrachloride-induced Hepatotoxicity. More studies of oriental medicinal herbs are required for developing a treatment of hepatotoxicity.

• Natural Product Sciences
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• v.17 no.4
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• pp.285-290
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• 2011

The rhizome of Alisma orientale Juzep (Alismataceae) has been used as a crude drug for diabetes, edema, inflammation and urinary disturbances in oriental medicine. Recent animal studies have shown that the extract of Alisma orientale rhizome (AOR) can potently lower high levels of serum lipids and improve insulin resistance, which are usually detected in patients and animals with non-alcoholic fatty liver disease. So, we studied the antioxidative effects of AOR extracts and fraction in vitro and their protective effects against acute hepatotoxicity induced by $CCl_4$ in vivo.. We then investigated the effects of each fraction on hepatotoxicity induced by tert-butyl hydroperoxide (t-BHP). DAOR (dichloromethane fraction of the Alisma orientale rhizome) scavenged free radicals and superoxide anions. DAOR protected against $CCl_4$ induced hepatotoxicity. DAOR had hepatoprotective and antioxidative effects against t-BHP-induced hepatotoxicity in HepG2 cells and in rats.

• Toxicological Research
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• v.13 no.3
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• pp.265-274
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• 1997

Uhwangchungsimwon(UC) is widely used as a herbal medicine on various circulatory disorders in Korea. The objective of this investigation was to characterize the acute, subacute hepatotoxic potency of orally administered UC in rats. In the acute and short-term studies, male rats of 150~170g were gavaged with 0, 7.5 g/kg once daily for up to 1, 5, 10 consecutive days. No differences in body weight, serum enzyme activities, absolute and relative liver weight and histopathological examination on liver between control and UC-fed groups were found. In the subacute study, UC was administered orally to both sexes of rats for 30 days(0, 1.875, 3.75 or 7.5 g/kg/day). There were no-doserelated hepatotoxic signs of general symptoms, body weight gain, water consumption and serum biochemical analysis. Slight decreases of food consumption observed at 3.75 and 7.5 g/kg groups of both sexes were due to be full of UC fed. Gross necropsy and histopathology revealed no evidence of hepatotoxicity related to UC. Our data indicate that hepatotoxicity was not caused by administration of UC up to 7.5 g/kg/dayfor 30 days in rats.