• Toxicological Research
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• 제13권3호
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• pp.237-245
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• 1997

As the development of a pharmaceutical product is a dynamic process which involves continuousfeed-back between non-clinical and clinical studies, the integration of pharmacokinetics into toxicity testing became increasingly important in recent years. Toxicokinetic measurements in the toxicity studies is considered to be an important scientific approach in the interpretation of the toxicology findings and the promotion of rational study design development. Primarily this research project was conducted to determine the systemic exposure achieved in acute toxicity test and its relationship to dose level and the time course of the toxicity study. Acute hepatotoxicity study and its relevant toxicokinetic study in mice were performed using acetarninophen (AA) as a model compound. The correlation between acute hepatotoxicity indices and toxicokinetic parameters following intraperitoneally administration of various dosages of AA in mice was evaluated and discussed minutely in the text. Based on these studies, single-dose toxicity testing of AA including kinetic studies was evaluated in ICR mice for 7 days and interpreted in the text. Our results from the integration of toxicokinetic monitoring into single-dose toxicity study enable to elucidate the relation of the exposure achieved in toxicity study to toxicological findings and assist in the selection of appropriate dose levels for use in repeated-dose toxicity or later studies.

• 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.

• 동의생리병리학회지
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• 제24권3호
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• pp.439-445
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• 2010

Pretreatment with Taraxacum Mongolicum H(TMH) prior to the administration of on $CCl_4$ significantly prevented the increased serum enzymatic activity of aminotransferase(ALT, AST), gamma-glutamyl transpeptidase(GGT) and bilirubin concentration in dose-dependent manner. In addition, pretreatment with TMH also significantly restored the elevation of hepatic malondialdehyde formation and the depletion of reduced glutathione content in the liver $CCl_4$-intoxicated rats. The restoration of microsomal aniline hydroxylase and aminopyrine N-demethylase activities indicated the improvement in functional status of endoplasmic reticulum. $CCl_4$-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. TMH showed antioxidant effects in $FeCl_2$-ascorbate-induced lipid peroxidation in rat liver homogenate and in superoxide radical scavenging activity. Our results suggest that the protective effect of TMH against $CCl_4$-induced hepatotoxicity possibly involve mechanisms related to its ability to block p450-mediated $CCl_4$ bioactivation and free radical scavenging effects.

• Food Science and Biotechnology
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• 제18권6호
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• pp.1411-1416
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• 2009

The suppressive effects of glutathione-enriched Saccharomyces cerevisiae FF-8 strain (FF-8 GY) on alcoholinduced hepatotoxicity have been studied. FF-8 GY (256 mg/L) from the fermentation at a large scale bioreactor was used. Either of 5% FF-8 GY or 5% commercial glutathione-enriched yeast extract (GYE) with or without 30% alcohol was tested with rats for 4 weeks. FF-8 GY and GYE were found to reduce those alcohol-elevated serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities. Blood alcohol and acetaldehyde were also decreased by FF-8 GY and GYE. Interestingly, FF-8 GY drastically increased both hepatic alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities in comparison to GYE group, thus FF-8 GY would be more effective in blood alcohol and acetaldehyde reduction. Attenuated lipid droplet accumulation in hepatocytes was observed in both FF-8 GY and GYE when alcohol stimulated the accumulation. Therefore, FF-8 GY may be useful to protect liver from alcohol-induced hepatotoxicity.

• 동의생리병리학회지
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• 제21권4호
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• pp.898-906
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• 2007

This study was to evaluate the effects of oral administration of Processed Sulphur on Hepatotoxicity. Processed Sulphur was administered orally to rats for 28 days. We measured the body and liver weight index, heamtological and biomedical parameters. We also observed the histopathological changes of liver in rats. No significant differences in body weight, liver weight index, heamtological and biomedical parameters and histopathological changes of hepatocyte between control and Processed Sulphur fed group were found. Our data indicate that hepatotoxicity was not caused by oral medication of Processed Sulphur up to 60mg/200g/day for 28 days in rats. Therefore, Processed Sulphur appears to be safe and non-toxic in these studies and a no-observed adverse effect level (NOAEL) in rats is established at 60mg/200g/day. The data could provide satisfactory preclinical evidence of safety to launch clinical trial on standardized formulation of mineral extracts.

• Toxicological Research
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• 제12권2호
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• pp.259-263
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• 1996

The preventive effects of ginseng and aloe extract on cigarette smoke-induced hepatotoxicity to Spague-Dawley rats were investigated. The experimental rats were exposed smoke by inhalation for 5 weeks, 3 times per day, and 15 minutes each time. Also ginseng and aloe extract (Group G+A), aloe (Group A) or ginseng (Group G) were administered to each group, but the positive control rats (Group C) were exposed smoke without any other special treatments. Group C showed decreased food intake and increased water consumption. Also the reduction of body weight and the increase in serumAST, ALT, triglyceride and alkaline phosphatase were observed. The relative liver weights of group C were increased and the hepatic parenchyma revealed light brownish red grossly. On histopathologic observation, the hepatocytes of group C animals exhibited diffuse swelling which narrowed the, sinusoidal lumen and disarrayed the hepatic cord-like arrangement. Diffuse necrosis of the hepatocytes was also observed. However, degeneration and necrosis of the hepatocytes were milder in group G+A. In the case of group A, the damage was moderate, while the group G showed marginal improvement from group C. Electronmicroscopically, peroxisome increased and mitochodria decreased in group C. Various hepatic damages related to smoking in group C revealed recovering tendency in group G+A. This study indicated that daily administration of ginseng and aloe could decrease and even prevent cigarette smokeinduced hepatotoxicity.

• Journal of Microbiology and Biotechnology
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• 제32권11호
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• pp.1447-1453
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• 2022

Prohibitin 1 (Phb1) is a pleiotropic protein, located mainly in the mitochondrial inner membrane and involved in the regulation of cell proliferation and the stabilization of mitochondrial protein. Acetaminophen (APAP) is one of the most commonly used over-the-counter analgesics worldwide. However, at high dose, the accumulation of N-acetyl-p-benzoquinone imine (NAPQI) can lead to APAP-induced hepatotoxicity. In this study, we sought to understand the regulation of mRNA expression in relation to APAP and GSH metabolism by Phb1 in normal mouse AML12 hepatocytes. We used two different Phb1 silencing levels: high-efficiency (HE, >90%) and low-efficiency (LE, 50-60%). In addition, the siRNA-transfected cells were further pretreated with 0.5 mM of Sadenosylmethionine (SAMe) for 24 h before treatment with APAP at different doses (1-2 mM) for 24 h. The expression of APAP metabolism-related and antioxidant genes such as Cyp2e1 and Ugt1a1 were increased during SAMe pretreatment. Moreover, SAMe increased intracellular GSH concentration and it was maintained after APAP treatment. To sum up, Phb1 silencing and APAP treatment impaired the metabolism of APAP in hepatocytes, and SAMe exerted a protective effect against hepatotoxicity by upregulating antioxidant genes.

• 한국식생활문화학회지
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• 제18권3호
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• pp.202-210
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• 2003

The purpose of this study was to investigate the effects of dietary purple sweet potato(Ipomoea batatas) powder on serum lipid levels and antioxidative enzymes in normal and pretective effect on hepatotoxicity rats induced by carbon tetrachlolide. Four groups of rats (3-week-old inbred Sprague-Dawley male rats) were normal rats fed control diet(C), induced hepatotoxicity rats fed control diet(EC), normal rats fed purple sweet potato diet(P), and induced hepatotoxicity rats fed purple potato sweet diet(EP). Rats were induced by single injection of 50% carbon tetrachlolide(0.1 mL/100 g B.W., i.p.). The rats were fed ad libitum each of the experimental diet for 5 weeks. After 5 weeks the rats were sacrificed and activities of antioxidant enzymes and lipid peroxidation products were determined in their liver homogenates. But serum concentrations of lipid was not significant in all groups. Serum alanine aminotransferase(ALT/GPT) and aspartate aminotransferase(AST/GOT) of the EC and EP groups were heigher than the C and P groups. The hepatic glucose 6-phosphatase(G6Pase) activity of the group fed purple potato diet(P) was lower than the other groups(p<0.05). However, The glutathione peroxidase(GPx) activities was not statistically different between the groups. Renal glutathione S-transferase(GST) activity of the EC and EP groups were lower than the C and P groups(p<0.05). In conclusion, these results suggest that purple sweet potato is believed to be possible protective effect on hepatotoxicity rats induced by carbon tetrachlolide.

• Nutrition Research and Practice
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• 제9권1호
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• pp.37-42
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• 2015

BACKGROUND/OBJECTIVES: Red grape seeds as functional food are a good source of important bioactive components such as phenolics and antioxidants, which decrease oxidative stress that contributes to the pathogenesis of hepatotoxicity. The current study was conducted in order to evaluate the protective effect of red grape dried seeds (RGDS) on antioxidant properties, lipid metabolism, and liver and kidney functions of rats with paracetamol (750 mg/kg) induced hepatotoxicity. MATERIALS/METHODS: RGDS was added to the basal diet at 5, 10, and 20%. Thirty five adult male rats were assigned to five groups (n = 7) for a six-week feeding period; group (1) normal control, group (2) induced control, groups (3, 4, and 5) fed a diet with RGPS at different levels, 5, 10, and 20%, respectively. At the end of the feeding period, animals' blood and tissues were collected for estimation of serum lipid profile, serum liver, and kidney biomarkers. The protection was measured by detecting lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), Catalase (CAT) (in liver tissues), and liver histological examination. RESULTS: The results showed a significant (P < 0.05) decrease in levels of serum cholesterol, triglycerides, low density lipoprotein (LDL-C), and very low density lipoprotein (VLDL-C), with a significant increase in level of high density lipoprotein (HDL-C) for RGDS groups compared to induced control. Rats administered a diet containing RGDS levels produced significant (P < 0.05) hepatoprotection by decreasing the activities of liver enzymes, kidney parameters, and lipid peroxidation, while levels of GSH, SOD, and CAT were increased significantly to near the normal levels. CONCLUSION: The RGDS 20% group was more effective than others against hepatotoxicity of paracetamol, which may be attributed to RGDS total phenols and antioxidant contents, which were 1.438 mg and 1.231 mg, respectively.