• Toxicological Research
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• v.29 no.3
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• pp.165-172
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• 2013

Acetaminophen (APAP) known as paracetamol is the main ingredient in Tylenol, which has analgesic and anti-pyretic properties. Inappropriate use of APAP causes major morbidity and mortality secondary to hepatic failure. Overdose of APAP depletes the hepatic glutathione (GSH) rapidly, and the metabolic intermediate leads to hepatocellular death. This article reviews the mechanisms of hepatotoxicity and provides an overview of current research studies. Pharmacokinetics including metabolism (activation and detoxification), subsequent transport (efflux)-facilitating excretion, and some other aspects related to toxicity are discussed. Nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene battery plays a critical role in the multiple steps associated with the mitigation of APAP toxicity. The role of Nrf2 as a protective target is described, and potential natural products inhibiting APAP toxicity are outlined. This review provides an update on the mechanism of APAP toxicity and highlights the beneficial role of Nrf2 and specific natural products in hepatoprotection.

• Biomolecules & Therapeutics
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• v.13 no.4
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• pp.232-239
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• 2005

An aqueous extract of oriental herbal composition named Onchengyeum and curcumin, an antioxidant isolated from turmeric (Curcuma Zonga L.) reduced hepatotoxicity induced by carbon tetrachloride ($CCI_4$). Improved liver function was observed by measuring the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine (CRE), total cholesterol (T-CHO), triglyceride (TG), low density lipoprotein cholesterol (LDL-CHO), high density lipoprotein cholesterol (HDL-CHO), total protein (TP), albumin (ALB) and total bilirubin (BIL) in serum. Hepatic parameters monitored were levels of cholesterol (CHO), triglyceride (TG), and malondialdehyde (MDA) and activities of cytochrome P450 (CYP), NADPH-CYP reductase, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx). The histopathological examination showed that the treatment of Onchengyeum and curcumin relieved the ballooning degeneration of hepatocytes which had been generated by $CCI_4$. The results suggested that hepatoprotective effects of Onchengyeum and curcumin possibly are due to their promising antioxidative activity.

• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.298-302
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• 1994

Wistar albino rats were injected subcutaneously with mercuric chloride (5 mg/kg) to define the early biochemical determinants that participate in the pathogenesis of mercuric chloride-induced hepatotoxicity, especially focusing on oxygen free radicals, we studied malondialdehyde(MDA) level and the activities of catalase and superoxide dismutase in the liver of rats at 24, 48 and 72 hr after the injection of mercuric chloride. MDA levels at 24, 48 and 72 hr after the injection of mercuric chloride increased as compared with that of control group. The activities of catalase and superoxide dismutase at 24, 48 and 72hr after the injection of mercuric chloride decreased as compared with that of control group. These results suggest that the depression of the activities of catalase and superoxide dismutase resulting from excessive oxygen free radicals is an important determinant in pathogenesis of mercuric chloride-induced hepatotoxicity.

• Journal of Life Science
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• v.9 no.4
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• pp.375-381
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• 1999

To evaluate the protective effects of extracts of silkworm on carbon tetrachloride-induced hepatotoxicity, serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase and lactic dehydrogenase activities, malondialdehydes values and glutathione-S-transferase activity were measured in ICR mice. Extracts of silkworm was administered orally at 30min after the administration of CCl4 Mice were sacrificed at 24h after the administration of extracts of silkworm. The activities of serum aminotransferase and the hepatic content of lipid peroxide after carbon tetrachloride treatment were markedly increased than normal control but those levels were decreased by the treatment of butanol soluble fraction of silkworm methanol extract. Glutathione S-transferase activity was decreased by carbontetrachloride than control, but also inhibited by the treatment of butanol soluble fraction of silkworm methanol extract.

• Environmental Analysis Health and Toxicology
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• v.7 no.1_2
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• pp.35-43
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• 1992

Mugwort has been used as a Korean folk medicine in treating liver diseases acting as an analgesics, sedative, diuresis, choleretics. This study was perfomed to evaluate the effect of mugwort extracts on the changes of enzyme activities, lipid accumulation of the serum and liver, when hepatotoxicity was induced by benzo(a)pyrene. The results are as follows: 1. Mugwort water extract administration prevented the increase of serum and liver AST, ALT, LDH, ${\gamma}$-GTP, liver ALP activities and bilirubin content caused by B(a)P injection. 2. The increase of serum and liver ALT, LDH, ${\gamma}$-GTP, serum AST activities and liver bilirubin contents in B(a)P treated group were decreased by mugwort methanol extract treatment. 3. Serum and liver total cholesterol, phospholipid, triglyceride level and serum HDL-cholesterol level were increased by B(a)P treatment. After combined treatment of mugwort water and methanul extracts, these lipid content were significantly decreased. 4. The hepatotropic effect of mugwort water extract and after-treatment against B(a)P induced hepatotoxicity was superior to that of methanol extract and pretreatment.

• Journal of the East Asian Society of Dietary Life
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• v.3 no.2
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• pp.121-128
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• 1993

This study was intended to clarify the protective mechanism of diallyl disulfide on the carbon tetrachloride-induced hepatotoxicity in mice. It was observed that a powerfully increment of serum alanine aminotransferase activity and hepatic lipid peroxide content after carbon tetrachloride injection were markedly inhibited by the pretreatment of diallyl disulfide (20mg/kg) for 5 days. It was also observed that hepatic aminopyrine demethylase and xanthine ocidase as free radical generating enzymes as well as superoxide dismutase and catalase activities as free frdical scavenging enzymes and hepatic glutathione content were not changed by the pretreatment with diallyl disulfide. But, treatment with diallyl disulfide did signifiantly increase cytosolic glutathione S-transferase activity. However, glutathione S-transferase activity in the presence of diallyl disulfide was not affected in vitro. Therefore, it is concluded that mechanism for the observed preventive effect ofdiallyl disulfide against the carbon tetrachloride-induced hepatotoxicity can be due to the engancement of glutathione S-transferase activity.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.165-165
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• 2001

The effects of betaine or taurine on hepatotoxicity induced by lipopolysaccharide (LPS) were examined in adult male SD rats. Rats were provided with drinking water containing either 1 % betaine or taurine for 2 weeks prior to challenge with LPS (5 mg/kg, iv). Supplement of betaine or taurine protected the animals from induction of LPS hepatotoxicity as measured by changes in aspartate aminotrassferase (AST), alanine aminotransferase (ALT) activities and total bilirubin levels in serum, and hepatic glutathione contents.(omitted)

• Toxicological Research
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• v.31 no.2
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• pp.137-149
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• 2015

Human hepatocytes, with complete hepatic metabolizing enzymes, transporters and cofactors, represent the gold standard for in vitro evaluation of drug metabolism, drug-drug interactions, and hepatotoxicity. Successful cryopreservation of human hepatocytes enables this experimental system to be used routinely. The use of human hepatocytes to evaluate two major adverse drug properties: drug-drug interactions and hepatotoxicity, are summarized in this review. The application of human hepatocytes in metabolism-based drug-drug interaction includes metabolite profiling, pathway identification, P450 inhibition, P450 induction, and uptake and efflux transporter inhibition. The application of human hepatocytes in toxicity evaluation includes in vitro hepatotoxicity and metabolism-based drug toxicity determination. A novel system, the Integrated Discrete Multiple Organ Co-culture (IdMOC) which allows the evaluation of nonhepatic toxicity in the presence of hepatic metabolism, is described.

• Journal of Food Hygiene and Safety
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• v.14 no.2
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• pp.172-178
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• 1999

Previous studies have shown that methanol extract and its butanol fraction of Carthamus tinctorius L. Semen have the hepatoprotective effect on the CCl4-induced hepatotoxicity. The hepatoprotective effect of subfractions has been evaluated by analyzing blood and hepatocyte biochemical analyses and biotransformation enzyme analyses. Treatment of BS-5, subfraction has significantly decreased the activities of alanine aminotransferase and aspartate aminotransferase. In addition, the levels of cholesterol and triglyceride in liver have been decreased as compared with that of CCl4 treated rats. The hepatoprotective effect of BS-5, subfraction on the CCl4-induced hepatotoxicity would be mediated of the attenuation of the level of cytochrome P450 and the enhancement of the activity of glutathion S-transferase.

• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.2
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• pp.326-332
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• 1998

The effect of mushroom extracts from Pleurotus ostreatus and Lentinus edodes on carbon tetrachloride(CCl4)-induced hepatotoxicity was investigated. Rats were administered orally each mushroom extract at the dose of 150mg/kg, foolwed by treatment with CCl4. Liver damage was produced in male Sprague-Dawley rats, after 21hrs from dosing with CCl4(0.25ml/kg) which were given intraperitoneally. Liver damage without renal injury was confirmed by measuring plasma enzyme, creatinine and blood analysis and liver analysis. Plasma aminotransferase activity, and levels of cholesterol and triglyceride were analyzed. Plasma alanine aminotransferase and aspartate aminotransferase activities were decreased by 34% and 61.5% in pretreatment group of Lentinus edodes compared with CCl4 treated group, respectively. The adminstration of all mushroom extracts led the plasma cholesterol and triglyceride levels decrease more than the CCl4-treated rats. These results suggest that Lentinus edodes extract protect liver from damage induced by CCl4.