• Journal of Applied Biological Chemistry
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• 제51권4호
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• pp.148-154
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• 2008

Excessive alcohol use causes oxidative stress in the liver, and antioxidant therapy has been an attractive approach for the treatment of ethanol-induced liver damage. The present study examined the hepatoprotective effect of Sasa quelpaertensis Nakai (Korean name, Jeju-Joritdae) in C57BL/6 mice intoxicated with ethanol. Mice were intraperitoneally administered with ethanol alone, or together with test materials three times at 12-h intervals. At 3 h after the last dosing, hepatotoxicity was assessed based on serum activities of aspartate aminotransferase and alanine aminotransferase, and hepatic contents of thiobarbituric acid-reactive substances and glutathione. Sasa quelpaertensis extract mitigated the acute ethanol hepatotoxicity as effectively as silymarin. Its n-butanol fraction was more active than methylene chloride or aqueous fraction. p-Coumaric acid, a major constituent of S. quelpaertensis, was found to effectively prevent the ethanol-induced hepatotoxicity. These data suggest that S. quelpaertensis and p-coumaric acid could be useful for the prevention of liver disease caused by alcohol abuse.

• Genomics & Informatics
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• 제7권2호
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• pp.97-106
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• 2009

Epigallocatechin gallate (EGCG), a well-known antioxidant molecule, has been reported to cause hepatotoxicity when used in excess. However, the mechanism underlying EGCG-induced hepatotoxicity is still unclear. To better understand the mode of action of EGCG-induced hepatotoxicity, we examined the effect of EGCG on human hepatic gene expression in HepG2 cells using microarrays. Analyses of microarray data revealed more than 1300 differentially expressed genes with a variety of biological processes. Upregulated genes showed a primary involvement with protein-related biological processes, such as protein synthesis, protein modification, and protein trafficking, while downregulated genes demonstrated a strong association with lipid transport. Genes involved in cellular stress responses were highly upregulated by EGCG treatment, in particular genes involved in endoplasmic reticulum (ER) stress, such as GADD153, GADD34, and ATF3. In addition, changes in genes responsible for cholesterol synthesis and lipid transport were also observed, which explains the high accumulation of EGCG-induced lipids. We also identified other regulatory genes that might aid in clarifying the molecular mechanism underlying EGCG-induced hepatotoxicity.

• 약학회지
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• 제40권3호
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• pp.320-325
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• 1996

In order to evaluate the protective effects of galangin on $CCl_4$-induced hepatotoxicity, GOT, GPT and malondialdehyde(MDA) values were measured in ICR mice. Galangin,a flavonoid compound, was administered orally for six days and immediately $CCl_4$ was injected intraperitoneally after the last dose of galangin. Mice were sacrificed at 24h after the administration of $CCl_4$. In the multiple pre-treatments for 6 consecutive days, galangin showed more potent protective effects than silymarin as reference active compound in serum GOT, GPT and MDA values in the liver at all doses tested. Antioxidative activity was determined by measuring the amounts of MDA formed from ethyl linoleate by $H_2O_2$ in vitro. Galangin showed higher inhibition than silymarin. These results demonstrate a possible hepato-protective role of galangin against $CCl_4$-induced hepatotoxicity in vivo and $H_2O_2$-induced lipid peroxidation in vitro. Therefore, galangin may be capable of protecting hepatotoxicity.

• Molecular & Cellular Toxicology
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• 제2권1호
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• pp.48-53
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• 2006

[ ${\alpha}-Naphthylisothiocyanate$ ] (ANIT) induces intrahepatic cholestasis, involving damage to biliary epitheial cells. This study investigates hepatic gene expression and histopathological alterations in response to ANIT treatment in order to elucidate early time response of ANIT-induced hepatotoxicity. ANIT was treated with single dose (3, 6, and 60 mg/kg) in corn oil by oral gavage. Serum biochemical and histopathological observation were performed for evaluation of hepatotoxicity level. Affymetrix oligo DNA chips were used for gene expression profile by ANIT-induced hetpatoxicity. Hepatic enzyme levels (ALT, AST, and ALP) were increased in 24 hr high dose group. In microscopic observations, moderate hepatocellular necrosis, were confirmed 24 hr high dose groups. We found that gene expression patterns were dependent on time and dose. Our selected genes were related inflammation and immunomodulation. In this study, ANIT-induced hepatotoxicity was involved in acute phase responses and provides evidence for role of neutrophil could be mechanism associated with ANIT-mediated hepatotoxicity.

• Biomolecules & Therapeutics
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• 제29권2호
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• pp.205-210
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• 2021

Over 30 million prescriptions of NSAIDs (non-steroidal anti-inflammatory drugs) are issued every year. Considering that these drugs are available without a prescription as over the counter (OTC) drugs, their use will be astronomical. With the increasing use of NSAIDs, their adverse effects are drawing attention. Especially, stomach bleeding, kidney toxicity, liver toxicity, and neurological toxicity are reported as common. Ibuprofen, one of the extensively used NSAIDs along with aspirin, can also induce liver toxicity, but few studies are addressing this point. Here we examined the liver toxicity of ibuprofen and investigated whether co-exposure to ethanol can manifest synergistic effects. We employed 2D and 3D cultured human hepatoma cells, HepG2 to examine the synergistic hepatotoxicity of ibuprofen and alcohol concerning cell viability, morphology, and histology of 3D spheroids. As a result, ibuprofen and alcohol provoked synergistic hepatotoxicity against hepatocytes, and their toxicity increased prominently in 3D culture upon extended exposure. Oxidative stress appeared to be the mechanisms underlying the synergistic toxicity of ibuprofen and alcohol as evidenced by increased production of ROS and expression of the endogenous antioxidant system. Collectively, this study has demonstrated that ibuprofen and EtOH can induce synergistic hepatotoxicity, providing a line of evidence for caution against the use of ibuprofen in combination with alcohol.

• Journal of Ginseng Research
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• 제12권2호
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• pp.114-120
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• 1988

We have studied the mechanism by examining the effect of ginseng on the epoxide hydrolase which is catabolized the reactive intermetabolite of bromobenzene, and bromobenzene-induced hepatotoxicity. It was observed that ginseng saponin fraction protects against bromobenzene-induced hepatotoxicity in mice as evidenced 1. increased the epoxide hydrolase activity, 2. lower serum transaminase activity, 3. decreased the formation of lipid peroxide. These results suggested that the inducing effect of ginseng on the epoxide hydrolase is believed to be a possible detoxication mechanism for the bromobenzene toxicity in mice.

• Toxicological Research
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• 제7권2호
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• pp.165-171
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• 1991

Effects of forced physical exercise on the CCl4 hepatotoxicity were examined in adult female rats. Rats were treated with CCl4 (2 mmol/kg, ip) and introduced into a cylindrical cage rotating at 9 rpm for 20 min/hr for 6 hr. Eighteen hr following the termination of exercise serum sorbitol dehydrogenase (SDH), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) activities and glucose-6-phosphatase activity were determined as parameters for hepatotoxicity. Physical exercise inhibited the $CCI_{4-}$induced increases in SDH, GOT, GPT activity, and glucose-6-phosphatase activity were determined as parameters for hepatotoxicity.

• Food Science and Biotechnology
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• 제17권2호
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• pp.413-416
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• 2008

Effects of extracts obtained from the flowers of Elsholtzia splendens on the serum lipid profile and hepatotoxicity in mice were investigated. Female ICR mice were given E. splendens ethanolic extract (ESEs) orally at a dose of 10 or 50 mg/kg BW for 50 days. Significant dose-dependent decreases in triglyceride and low-density lipoprotein (LDL)-cholesterol of serum were observed. In addition, ESEs prolonged the lag-time of LDL oxidation in vitro. In the serum of ICE mice given ESEs orally at 10 and 50 mg/kg BW, the serum levels of aspartate aminotransferase (AST) and lactic dehydrogenase (LDH) increased significantly, while total protein, albumin, creatinine, alanine aminotransferase (ALT), and total bilirubin did not change. Therefore, ESEs may be beneficial to human health, although it has some hepatotoxicity.

• 한국환경보건학회지
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• 제32권3호
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• pp.235-239
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• 2006

Cichorium intybus (Compositae) has been used for fevers, dyspepsia, headache and jaundice, as a demulcent. Also, it has relaxation effects and relief effects against coffee and teas, and is widely used as food. We investigated anti-lipid peroxidative effects and liver protective activity on $CCl_4$ induced lipid peroxidation and hepatotoxicity in rats. MeOH Ex. enhanced the inhibition of anti-lipid peroxidative effects in liver lipid. In chemical parameters obtained from serum analysis, MeOH Ex. revealed significant decrease on hepatotoxicity. The results were as follows; 1. The inhibitory effects of lipid peroxidation were shown in accordance with the increase of samples' concentration level. 2. In chemical parameters obtained from serum analysis, the activities of GOT, GPT, AlP were restored to near the normal level. The contents of cholesterol and BUN showed inhibitory effects with valence. 3. The weights of liver and spleen were not able to restore to the normal level. But on a general level, they were reduced more than the control group.

• Journal of Pharmaceutical Investigation
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• 제25권4호
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• pp.313-322
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• 1995

The covalent conjugation of human recombinant superoxide dismutase (hrSOD) with trichloros-triazine activated polyethylene glycol (PEG) 5000 formed soluble conjugates with molecular weight of 92KD, which retained $90{\sim}98%$ of original activity with a markedly prolonged plasma half-life of enzyme activity. The effect of hrSOD-PEG conjugates on acetaminophen (ACP)-induced hepatotoxicity was tested in male rats which were pretreated with 3-methylcholanthrene. HrSOD-PEG conjugates inhibited the hepatotoxicity produced by ACP, on the other hand, native hrSOD had no protective effect. The above results indicated that oxygen radicals might participate in the mechanism of the ACP-induced hepatotoxicity and that polymer conjugated-protein drugs with prolonged half-lives could be employed as an effective therapeutic agent.