• Journal of The Korean Society of Clinical Toxicology
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• v.16 no.2
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• pp.149-156
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• 2018

Purpose: The purpose of this study was to determine whether hepatotoxicity could be predicted early using biochemical markers in patients with acetaminophen (AAP) poisoning and to assess the usefulness of predictive factors for acute liver injury or hepatotoxicity. Methods: This study was a retrospective observational study involving a medical records review. The participants were patients who were admitted to the emergency department (ED) with AAP overdose at two hospitals over a 10-year period. Demographic data, age, time from ingestion to visit, initial AAP level, initial hepatic aminotransferases, and initial prothrombin time were recorded. Acute liver injury was defined as a peak serum ALT >50 U/L or double the admission value, and hepatotoxicity was defined as a peak ALT >1,000 U/L. Receiver operating characteristic curve analyses were performed to compare the prognostic performance among variables. Results: A total of 97 patients were admitted to the ED with AAP overdose, of whom 26 had acute liver injury and 6 had hepatotoxicity. Acute liver injury was associated with the time interval after taking the drug, and hepatotoxicity was associated with the initial PT and the ALT level. The scoring system proposed by the authors has a significant ability to predict both acute liver injury and hepatotoxicity. Conclusion: To predict the prognosis of AAP poisoning patients, the time interval after taking AAP was important, and initial prothrombin time and ALT level were useful tests. Also a scoring system combining variables may be useful.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.410-413
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• 2006

This study was done to investigate the protective effects of Iljungbogan-Tang on acute hepatotoxicity of rats induced by $CCL_4$ and acetaminophen. The subject animals were divided into 3 groups : control group(administrated 0.5% carboxymethyl cellulose), sample group(30, 100, 300, 600mg/kg administrated), positive control group (administrated silymarine), Acute hepatotoxicity of rats were induced by $CCL_4$ and acetaminophen, and the serum transaminase(AST, ALT) were measured for enzyme activities. The inhibitory effects on the serum AST activities were noted in sample group(100, 300, 600mg/kg administrated) on hepatotoxicity of rats induced by $CCL_4$. The inhibitory effects on the serum AST, ALT activities were noted in sample group(30mg/kg administrated) on hepatotoxicity of rats induced by acetaminophen. The inhibitory effects on the serum AST activities were noted in sample group(600mg/kg single dose administrated) on hepatotoxicity of rats induced by acetaminophen. It is considered that Iljungbogan-Tang has protective effects against hepatotoxicity in rats induced by $CCL_4$ and acetaminophen. So it is required to study about the actions of mutual relation of medicines and patho-mechanism through experiment.

• Toxicological Research
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• v.13 no.3
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• pp.265-274
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• 1997

Uhwangchungsimwon(UC) is widely used as a herbal medicine on various circulatory disorders in Korea. The objective of this investigation was to characterize the acute, subacute hepatotoxic potency of orally administered UC in rats. In the acute and short-term studies, male rats of 150~170g were gavaged with 0, 7.5 g/kg once daily for up to 1, 5, 10 consecutive days. No differences in body weight, serum enzyme activities, absolute and relative liver weight and histopathological examination on liver between control and UC-fed groups were found. In the subacute study, UC was administered orally to both sexes of rats for 30 days(0, 1.875, 3.75 or 7.5 g/kg/day). There were no-doserelated hepatotoxic signs of general symptoms, body weight gain, water consumption and serum biochemical analysis. Slight decreases of food consumption observed at 3.75 and 7.5 g/kg groups of both sexes were due to be full of UC fed. Gross necropsy and histopathology revealed no evidence of hepatotoxicity related to UC. Our data indicate that hepatotoxicity was not caused by administration of UC up to 7.5 g/kg/dayfor 30 days in rats.

• Toxicological Research
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• v.13 no.3
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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.

• YAKHAK HOEJI
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• v.23 no.1
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• pp.41-49
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• 1979

By intraperitoneal administration of thioacetamide to rats, acute liver injury was produced. In these rats, the level of serum GOT and GPT activities showed a remarkable increase and the principal histopathologic change was centrilobular hepatic necrosis. In this study, combined administration of silymarin with promethazine hydrochloride to the rats with acute liver injury which was produced by thioacetamide inhibited the increase of serum transaminase activities and protected the histopathologic change, showing comparatively more improved results than simple administration of silymarin alone. On the basis of these results, it is suggested that promethazine hydrochloride potentiates the effectiveness of silymarin in acute thioacetamide hepatotoxicity of rats.

• Journal of Pharmacopuncture
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• v.10 no.1 s.22
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• pp.101-107
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• 2007

Objectives : This study was aimed at investigating liver protection mechanism of Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese by inducing liver toxicity through $CCl_4$ and t-BHP in mice and evaluated serological findings. Methods : Experiment groups was categorized into untreated normal group, treated control group, and orally administered Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese experimental groups. At the termination of experiment, gross examination of the liver as well as Total bilirubin, AST, and ALT contents in the serum were evaluated. Results : 1. In the $CCl_4$ induced acute hepatotoxicity test, total bilirubin, AST and ALT didn't show significant differences between the control and experimental groups. 2. In the t-BHP induced acute hepatotoxicity test, total bilirubin, AST and ALT didn't show significant differences between the control and experimental groups. Conclusion : Taken together, Cultivated Ginseng and Cultivated Wild Ginseng of Korean and Chinese cannot be effectively used for recovering the liver functions in acute hepatotoxicity tests using $CCl_4$ and t-BHP. Further researches, for example treated long period, must be tried to verify the efficacies.

• Journal of The Korean Society of Clinical Toxicology
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• v.6 no.1
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• pp.1-8
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• 2008

Acetaminophen (AAP) overdose can result in potentially serious hepatotoxicity. The ingested dose and time from ingestion to presentation are important prognostic factors. Toxic dose in adult is thought to be at least 10 g or 200 mg/kg. However, early management of acute overdose should be guided by the plasma AAP concentration. The antidote for AAP poisoning is N-acetylcysteine (NAC). It provides complete protection against hepatotoxicity if given within 8 h of acute overdose. If the concentration is above the possible toxicity line as predicted by the Rumack-Matthew nomogram, either the 72-hr oral or the 20-hr intravenous NAC regimen should be administered. NAC is also effective if started late in patients with established hepatic failure. This article summarizes the current consensus of clinical assessment and management for acute AAP overdose.

• Nutrition Research and Practice
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• v.3 no.2
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• pp.95-101
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• 2009

It has been reported that dietary polyunsaturated fats (PUFA) increase liver injury in response to ethanol feeding. We tested the hypothesis that diets rich in linoleic acid (18:2n-6) would affect acute liver injury after acetaminophen injection and that protein restriction might exacerbate the liver injury. We examined effects of feeding diets with either 15% (wt/wt) corn oil or 14% beef tallow and 1% corn oil for six weeks with either 6 or 20 g/100 g protein on acute hepatotoxicity. After the feeding period, liver injury was induced by injecting either with 600 mg/kg body weight acetaminophen suspended in gum arabic-based vehicle, or with vehicle alone during fasting status. Samples of liver and plasma were taken for analyses of hepatic glutathione (GSH) levels and liver-specific enzymes [(Glutamate-pyruvate transaminase (GPT) and glutamate-oxaloacetate transaminase (GOT)], respectively. Whereas GSH level was significantly lower in only group fed 15% corn oil with 6 g/100 g protein among acetaminophen-treated groups, activities of GPT and GOT were significantly elevated in all groups except the one fed beef tallow with 20 g/100 g protein, suggesting low protein might exacerbate drug-induced hepatotoxicity. The feeding regimens changed the ratio of 18:2n-6 to oleic acid (18:1n-9) in total liver lipids approximately five-fold, and produced modest changes in arachidonic acid (20:4n-6). We conclude that diets with high 18:2n-6 promote acetaminophen-induced liver injury compared to diets with more saturated fatty acids (SFA). In addition, protein restriction appeared to exacerbate the liver injury.

• YAKHAK HOEJI
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• v.51 no.5
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• pp.296-300
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• 2007

The purpose of this study was to investigate the preventive effects of Lycii fructus Extract (LFE) against the acute hepatotoxicity-inducing lipopolysaccharide (LPS) in the liver. LFE of 100 mg/kg concentration was intraperitoneally administered into rats at dose of 1.5 ml/kg for 20 days. On the day 21, 1.5 ml/kg of LPS dissolved in saline was injected 4 hours before anesthetization. We examined the levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), lactate dehydrogenase (LDH) in serum of rats, superoxide dismutase (SOD) in mitochondrial fraction, and malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPx) in liver homogenate. LPS-treatment markedly increased the levels of GOT, GPT, LDH and MDA, and significantly decreased those of SOD, CAT and GPx. But LFE-pretreatment decreased the levels of GOT, GPT, LDH and MDA, by 17.7%, 27.5%, 40.7% and 56.9%, respectively and increased those of SOD, CAT and GPx, by 90.5%, 78.9% and 83.8%, respectively. These results showed that the LFE had the preventive effects against the acute hepatotoxicity-inducing LPS in the liver.

• Toxicological Research
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• v.25 no.2
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• pp.85-92
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• 2009

4,4'-Methylenedianiline (MDA) is an aromatic amine that is widely used in the industrial synthetic process. Genotoxic MDA forms DNA adducts in the liver and is known to induce liver damage in human and rats. To elucidate the molecular mechanisms associated with MDA-induced hepatotoxicity, we have identified genes differentially expressed by microarray approach. BALB/c male mice were treated once daily with MDA (20 mg/kg) up to 7 days via intraperitoneal injection (i.p.) and hepatic damages were revealed by histopathological observation and elevation of serum marker enzymes such as AST, ALT, ALP, cholesterol, DBIL, and TBIL. Microarray analysis showed that 952 genes were differentially expressed in the liver of MDA-treated mice and their biological functions and canonical pathways were further analyzed using Ingenuity Pathways Analysis (IPA). Toxicological functional analysis showed that genes related to hepatotoxicity such hyperplasia/hyperproliferation (Timp1), necrosis/cell death (Cd14, Mt1f, Timp1, and Pmaip1), hemorrhaging (Mt1f), cholestasis (Akr1c3, Hpx, and Slc10a2), and inflammation (Cd14 and Hpx) were differentially expressed in MDA-treated group. This gene expression profiling should be useful for elucidating the genetic events associated with aromatic amine-induced hepatotoxicity and for discovering the potential biomarkers for hepatotoxicity.