• Toxicological Research
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• v.3 no.2
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• pp.129-141
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• 1987

Hepatocytes isolated from rats which have been pretreated with phenobarbital (80 mg/kg for 3 days), were able to take up N-acetylcysteine from surrounding medium and were able to synthesize the reduced glutathione ($GSH^{\ast}-3$) intracellularly. The N-acetylcysteine is quickly deacetylated after the uptake and increases the pool size of cysteine, which was very low initially (5 nmol/$10^6$ cells). From this increased intracellular cysteine pool, GSH was synthesized. Freshly isolated rat hepatocytes contained a high level of GSH (30 nmol/$10^6$ cells), but upon incubation with the diethylmaleate, it was markedly decreased (10 nmol/$10^6$ cells). The hepatocytes with depleted GSH have lost viability upon incubations with acetaminophen (5mM) and paraquat (2 mM). However, when the N-acetylcysteine (1 mM) was added to this incubation condition, these chemical induced hepatocellular necrosis were prevented for longer durations. This N-acetylcysteine dependent protective effect against the hepatotoxic chemicals was lost by adding methionine sulfoximine (10 mM), an inhibitor of GSH biosynthesis. Both the carbontetrachloride (5 mM) and chioroform (5 mM) added to the incubation medium caused rapid losses of GSH and cell viability, even without the prior depletion of cellular GSH. However, again, if the 1mM N-acetylcysteine was supplemented, the rates of losses of GSH and cell viability were retarded in both cases. Even though large amounts of the added N-acetylcysteine was present in the cell, N-acetylcysteine conjugate of acetaminophen was not formed. Instead, only large amounts of GSH conjugate of the drug was produced. Thus, it is concluded that the added N-acetylcysteine is taken up and utilized for resynthesis of GSH. In turn, this resynthesized GSH contributes to the protection against cytotoxicity inducible with hepatotoxic drugs.

• 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.

• Advances in Traditional Medicine
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• v.7 no.3
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• pp.297-303
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• 2007

The ethyl acetate fraction (EAF) and n-butanol fraction (NBF) of ethanolic extract of Bacopa monnieri aerial parts were screened for hepatoprotective activity and in vivo antioxidant activity on ethanol-induced hepatotoxic rats. Ethyl acetate fraction was found to be more potent even though both the fractions were endowed with significant hepatoprotective activity. EAF and NBF were investigated for hepatoprotective activity in albino rats at 300 mg/kg, p.o. dose and compared with standard drug Silymarin (25 mg/kg, p.o.). Results show that both the fractions were effective in blunting ethanol-induced enhanced activities of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, level of serum bilirubin (both total and direct), liver weight loss and was also effective in reducing ethanol-induced lipid peroxidation both in vitro and in vivo. Furthermore, the fractions could also enhance ethanol-induced suppressed activities of superoxide dismutase, catalase and decreased level of reduced glutathione. Results of hepatocellular damage caused by ethanol and its recovery by EAF and NBF, suggest that they might be considered as a potential source of natural hepatoprotective agents, which could be related to the free radical scavenging properties of saponins present in high concentration in the fractions.

• Journal of Pharmacopuncture
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• v.23 no.3
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• pp.124-141
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• 2020

Objectives: Several toxins and molecules are able to damage the liver, causing the hepato-toxicity. This disorder can be protected naturally, by some essential oils obtained from different plants. In this review we are cited some of these compounds that have been tested by their hepatoprotective effect. Methods: We reviewed 83 articles published between 1981 and 2018 in English via three databases Sciencedirect, Springer and PubMed. So, we have used the keywords: Hepatoprotective effect, liver disease, plants and essential oils. Results and conclusion: In this work, we classified the plants; contain the essential oils, in alphabetical order as a table containing the scientific, family names, information plants, the experimental assay and the results obtained from the hepatoprotective studies. We have described 27 species belonging to 12 families: Lamiaceae (7 species), Asteraceae (6 species), Umbellifereae (3 species), Apiaceae (3 species) are the main families which enclose the species that was studied. The study also includes the major compounds isolated from some of these essential oils. The most of those compounds belong to terpene class essentially cineol, carvacrol and thymol. Thus, the different essential oils that have been cited in this review were shown that have an antioxidant activity.

• Journal of Yeungnam Medical Science
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• v.4 no.1
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• pp.89-96
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• 1987

Carbon tetrachloride and Dimethylnitrosamine, both potent hepatotoxic agents, affect the hepatic lobules with fatty changes and central necrosis, and hemorrhagic necrosis. To study the effects on morphologic changes of the hepatic lobules in cases of single and repeated treatment of both hepatotoxins, sublethal doses of carbon tetrachloride, 0.4ml/kg, and dimethylnitrosamine, 40mg/kg of rats were given intraperitoneally single, twice and triple. With interval of 3 days, and the results were as follows : 1. The fatty changes and central necrosis of the hepatic lobules were milder and more quickly disappeared in the rats with twice or triple treatment than single administration of carbon tetrachloride, and regenerative changes of hepatic and sinusoidal cells achieved fater in the rats with repeated administration of carbon tetrachloride than those with single treatment. 2. The hemorrhagic necrosis of the hepatic lobules was not significantly influenced by the times of DMN treatment, but the hyperplastic changes showed more active to animals, with multiple administration of DMN.