• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.126-133
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• 2006

Thioacetamide (TA) is well known hepatotoxic and hepatocarcinogenic agent. TA also diminishes the contents of hepatic cytochrome P450 and inhibits the enzyme activity of the hepatic mixed function oxidases. TA metabolite, thioacetamide-s-oxide, is further transformed into a still unknown highly reactive metabolite that binds to macromolecules. In this study, we focused on TA-induced gene expression at hepatotoxic dose. Mice were exposed to two levels (5 mg/kg or 50 mg/kg i.p.) of TA, sampled at 6 or 24 h, and hepatic gene expression levels were determined to evaluate dose and time dependent changes. We evaluated hepatotoxicity by serum AST and ALT level and histopathological observation. Mean serum activities of the liver leakage enzymes, AST and ALT, were slightly increased compare to control. H & E and PAS evaluation of stained liver sections revealed TA-associated histopathological finding in mice. Centrilobular eosinophilic degeneration was observed at high dose-treated mice group. Hepatic gene expression was analyzed by QT clustering. Clustering of high dose-treated samples with TA-suggests that gene expressional changes could be associated from toxicity as measured by traditional biomarkers in this acute study.

• Archives of Pharmacal Research
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• v.26 no.11
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• pp.943-950
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• 2003

In the present studies, the acute toxic effects of 2-bromopropane (2-BP) and its analog, 1,2-dibromopropane (1,2-DBP), were investigated in female BALB/c mice. The mice were treated orally with either 2-BP at 2000 and 4000 mg/kg or 1,2-DBP at 300 and 600 mg/kg. Four days before necropsy, the mice were immunized intraperitoneally with sheep red blood cells (SRBCs). 1,2-DBP reduced the weights of the spleen and thymus weights and decreased the number of splenic cells. In addition, treatment with 1,2-DBP suppressed the antibody response to SRBCs. Meanwhile, only the antibody response was significantly suppressed by treatment with 2-BP. In the subsequent studies, the time course effects of 2-BP and 1 ,2-DBP on the hepatotoxic parameters were compared in female BALB/c mice. When mice were treated orally with either one of these chemicals for 6, 12, 24 and 48 h, the activities of serum alanine aminotransferase and aspartate aminotransferase elevated significantly only with 1,2-DBP 24 h after the treatment. The hepatic content of glutathione was reduced by 1,2-DBP. Meanwhile, these parameters were increased by 2-BP. The present results suggest that 1,2-DBP in the Solvent 5200 also contributes to the immnunotoxicity, although 2-BP is a major component.

• Natural Product Sciences
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• v.9 no.1
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• pp.13-17
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• 2003

The hepatoprotective effect of the ethanolic extract of Coccinia indica fruits in rats treated with carbon tetrachloride. In hepatotoxic rats, liver damage was studied by assessing parameters such as aspartate aminotransferase (AST), alanine aminotransferase (AlT), alkaline phosphatase (AIP) and gamma glutamyl transpeptidase (GGT) in serum, and concentrations of total proteins, total lipids, phospholipids, triglycerides and cholesterol in both serum and liver. The effect of co-administration of ethanolic extract on the above parameters was further investigated. Histopathological study of the liver in experimental animals was also undertaken. Hepatic damage as evidenced by a rise in the levels of AST, AIT, AIP and GGT in serum, and also changes observed in other biochemical parameters In serum and liver showed a tendency to attain near normalcy in animals co-administered with the extract. The normal values for AST (IU/L), AIP (IU/I), protein (g/100 ml) and total lipids (mg/100 ml) in serum (i.e.,20.24, 70.04, 5.72 and 135.54 respectively) were found to alter towards values 32.61, 127.11, 3.83 and 265.91 in hepatotoxic rats. These parameters Attained near normal values (I.e.,22.82, 79.30, 5.22 and 151.24 for AST, AIP protein and total lipids respectively) in ethanolic extract co-administered rats. Profound steatosis, ballooning degeneration and nodule formation observed in the hepatic architecture of $CCl_4$ treated rats were found to acquire near-normalcy in drug co-administered rats, thus corroborating the biochemical observations. Thus the study substantiates the hepatoprotective potential of ethanolic extract of Coccinia indica fruits.

• Journal of Ginseng Research
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• v.32 no.2
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• pp.161-170
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• 2008

The aim of this meta-analysis was to systematically investigate the anti-hepatotoxic effect of ginseng in rats induced toxicity which damage to liver. Primary researches were gained on the ScienceDirect database, the DBpia, and the KISS, and the data about the effect factors in plasma and in enzyme were listed as many as possible. The effect factors were alanine transaminase (ALT), aspartate transaminase (AST), liver aminopyrine N-demethylase (AD), liver aniline hydroxylase (AH), liver 3,4-Methylenedioxyamphetamine (liver MDA), cytochrome P450 (P450), serum alkaline phosphatase (ALP), serum lactate dehydrogenase (LDH), cytochrome b5 (Cyto b5), glutathione reductase (GR), Liver glutathione S-transferase (GST), liver glutamyltransferase (GT), Liver (${\gamma}-GCS$), serum liver 3,4-Methylenedioxyamphetamine (serum MDA), serum sorbitol dehydrogenase (SDH), serum total protein (TP), serum ${\gamma}-glutamyltransferase$ (${\gamma}-GT$). To investigate the effect of ginseng, the mean difference (MD) between the group of rats induced by toxicity (RH) and the group of rats induced by toxicity with ginseng (RHG) were combined, and the significance of MDs were tested. The combined MDs were checked the biases caused by heterogeneity among studies and the publication biases, and adjusted by using random effect model and trim and fill method, respectively. The effect about ALT, AST, ALP, LDH, SDH, TP and ${\gamma}-GT$ in plasma factors were significant, and about AD, liver MDA, P450, Cyto b5, GR, GST, GT and ${\gamma}-GCS$ in enzyme factors were significant. The treatment with ginseng supplementation was significantly effected on plasma and enzyme factors of damaged-rats.

• YAKHAK HOEJI
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• v.55 no.4
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• pp.352-360
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• 2011

Standard combination chemotherapy including isoniazid, rifampin, pyrazinamide, and ethambutol is very effective against tuberculosis. But, these medicines can cause hepatotoxicity which is the main reason for treatment interruption or change in drug regimen. In order to identify risk factors associated with hepatotoxcity in Koreans and assess elevated baseline LFTs' contributions to hepatotoxicity, a retrospective case control study was performed. The medical records of 277 patients who diagnosed with tuberculosis at a community hospital from January 1st, 2007 to June 30th, 2010 were reviewed. Patients were categorized into 3 groups (non toxic group, patients without increase in LFT levels; mild to moderate hepatotoxic group and severe hepatotoxic group). And the correlation between risk factors and hepatotoxicity was analyzed by using SPSS program. The overall incidence of hepatotoxicity was 18% and 8.7% of patients developed severe toxicity. Patients in the severe toxic group had the longest treatment period among the three groups. In 75% of severe toxic group, hepatotoxicity occurred within 18.3 days after starting medication. Hypoalbuminemia (serum albumin <3 g/dl) was a significant risk factor for development of severe toxicity. Elevated baseline transaminase (except ALT), total bilirubin, and preexisting hepatitis were also risk factors which were more than twice as likely to increase risk of severe hepatotoxicity (p>0.05). In conclusion, hypoalbuminemia (serum albumin level <3 g/dl) was a significant risk factor for anti-tuberculosis druginduced severe toxicity. Therefore, before starting antituberculosis chemotherapy, serum albumin level should be assessed at baseline. In high-risk patients (hypoalbuminemia, elevated LFTs) for hepatotoxicty, liver function should be closely monitored up to at least 21 days after taking medication.

• Korean Journal of Food Science and Technology
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• v.35 no.1
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• pp.138-143
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• 2003

Total methanolic extract of Chrysanthemum coronarium L. var. spatiosum (Compositae) was revealed to have anti-hepatotoxic activity against galactosamine-induced toxicity on primary cultured rat hepatocytes. After successive partitioning with chloroform, n-butanol, and water, the chloroform fraction showed a significant inhibition activity of 51% at 50 ppm, compared with that of silybin, 45.9% at $100\;{\mu}M$. The chloroform fraction was subjected to silica gel column chromatography and yielded active CH-II, CH-V and CH-VI subfractions, and the anti-hepatotoxic activity of these subfractions were 47.6, 56.3, and 23.2%, respectively, at 50 ppm. Total glutathione contents of CH-II, CH-V, and CH-VI increased by 49.8, 43.9, and 47.5% of the control, respectively at 50 ppm, whereas that of silymarin was, 59.7% at $100\;{\mu}M$ after challenged with galactosamine. The ratio of (reduced glutathione) / (total glutathione) in CH-II, CH-V and CH-VI subfraction showed similar values of $0.86{\sim}0.87$ at 50 ppm, whereas that of silymarin was, 0.85 at $100\;{\mu}M$. The incorporation of $[^3H]-uridine$ uptake into RNA was not affected by these active subfractions.

• Journal of Ginseng Research
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• v.14 no.2
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• pp.217-220
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• 1990

Two lignanes, Comp.-I, mp 108-1$0^{\circ}C$ and Comp.-II 50-52$^{\circ}$were isolated from Korea ginseng extract by repeated column chromatographic purification. Comp.-I was identified as gomisin-N and Comp.-II as gomisin-A by spectrometric analysis, both of which have already been described as the anti-hepatotoxic lignan components of Schizandra chinesis Bail.

• Environmental Analysis Health and Toxicology
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• v.7 no.1_2
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• pp.45-51
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• 1992

This study was performed to investigate the effect of Angelicae gigantis Radix extract oil the hepatic detoxifying enzyme activities and lipids. Male sprague-dawley rats were administrated the extracts with benzo(a)pyrene, a hepatotoxic agent, inducing liver damages. Results obtained from this study were as follows: 1. The markedly increased enzyme activities (AST, ALT, LDH, ALP, ${\gamma}$-GTP, GSH-Px) in B(a)P induced groups tended to be decreased by the treatment of the Angelicae gigantis Radix extract. 2. Liver GSH content and lipid peroxide activity were decreased by the administration of the extracts. 3. It tended that the curative effects were better than the protective effects of the extracts.

• Environmental Analysis Health and Toxicology
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• v.19 no.2
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• pp.201-206
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• 2004

Recently, waste plastic recycling technology is transforming from Incineration system to pyrolysis gasification system which can derive the resources from environmental waste and charge no more environmental burden to nature. The present study was carried out to investigate the potential acute toxicity of derived product of pyrolysis gasifications system for recycling of waste plastic by a single oral dose in Sprague-Dawley Rats. In order to evaluate the hepatotoxic effects of derived product of pyrolysis gasification system, activities of serum transaminase were measured in rats. No related changes in survivals, clinical signs and the ratio of the liver to body weights of rats were monitored. The results showed that the single oral administration of material of pyrolysis system for recycling of waste plastic did not induce any toxic effect at orally single dose level of 0 and 100, 200, 400, 800mg/kg body weight in rats. We could not find out any significant tocxicity induced by single oral administrate of material of pyrolysis system for recycling of waste plastic.

• Natural Product Sciences
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• v.6 no.3
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• pp.126-130
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• 2000

Tiliacora racemosa Colebr. belonging to the family Menispermaceae, is the biggest storehouse of diphenyl bisbenzylisoquinoline (DBBI) alkaloids. Exhaustive chemical processing of the root of T. racemosa by the application of modern separation techniques yielded a DBBI alkaloid which was identified as tiliacorine using sophisticated spectroscopic methods (UV, IR, $^1H-NMR$, MS). Haematological study with tiliacorine proved that there was no abnormal haematological results in comparison with the normal values. Chronic toxicity study with tiliacorine revealed that the alkaloid is devoid of any hepatotoxic and nephrotoxic action.