• Journal of Ginseng Research
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• v.41 no.2
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• pp.159-168
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• 2017

Background: Radiotherapy is one of the most important modalities in cancer treatment; however, normal tissue damage is a serious concern. Drug development for the protection or reduction of normal tissue damage is therefore a clinical issue. Herein, we evaluated the protective properties of Panax ginseng Meyer and its corresponding mechanisms. Methods: C56BL/6 mice were orally pretreated with P. ginseng water extract (PGE; 25 mg/kg, 50 mg/kg, or 100 mg/kg) or intraperitoneally injected melatonin (20 mg/kg) for 4 d consecutively, then exposed to 15-Gy X-ray radiation 1 h after the last administration. After 10 d of irradiation, the biological properties of hematoxicity, fat accumulation, histopathology, oxidative stress, antioxidant activity, pro-inflammatory cytokines, and apoptosis signals were examined in the hepatic tissue. Results: The irradiation markedly induced myelosuppression as determined by hematological analysis of the peripheral blood. Steatohepatitis was induced by X-ray irradiations, whereas pretreatment with PGE significantly attenuated it. Oxidative stress was drastically increased, whereas antioxidant components were depleted by irradiation. Irradiation also notably increased serum liver enzymes and hepatic protein levels of pro-inflammatory cytokines. Those alterations were markedly normalized by pretreatment with PGE. The degree of irradiation-induced hepatic tissue apoptosis was also attenuated by pretreatment with PGE, which was evidenced by a terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick-end labeling assay, western blotting, and gene expressions analysis, particularly of apoptotic molecules. Conclusion: We suggest that PGE could be applicable for use against radiation-induced liver injury, and its corresponding mechanisms involve the modulation of oxidative stress, inflammatory reactions, and apoptosis.

• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.112-121
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• 2017

Drug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity. We identified the innately and differentially expressed genes of mice susceptible to APAP-induced hepatotoxicity in the pre-biopsied liver tissue before APAP treatment through microarray analysis of the global gene expression profiles (Affymetrix $GeneChip^{(R)}$ Mouse Gene 1.0 ST for 28,853 genes). Expression of 16 genes including Gdap10, Lpl, Gabra3 and Ccrn4l were significantly different (t-test: FDR <10%) more than 1.5 fold in the susceptible animals than resistant. To confirm the association with the susceptibility to APAP-induced hepatotoxicity, another set of animals were measured for the expression level of selected 4 genes (higher two and lower two genes) in the liver pre-biopsy and their sensitivity to APAP-induced hepatotoxicity was evaluated by post hoc. Notably, the expressions of Gabra3 and Lpl were significantly correlated with the severity of liver injury (p<0.05) demonstrating that these genes may be linked to the susceptibility to APAP-induced hepatotoxicity.

• BMB Reports
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• v.38 no.3
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• pp.300-306
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• 2005

Tamoxifen citrate is an anti-estrogenic drug used for the treatment of breast cancer. It showed a degree of hepatic carcinogenesis, when it used for long term as it can decrease the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in liver rat cells leading to liver injury. In this study, a model of liver injury in female rats was done by intraperitoneal injection of tamoxifen in a dose of 45 mg/kg body weight for 7 successive days. This model produced a state of oxidative stress accompanied with liver injury as noticed by significant declines in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) in a dose of 200 mg/kg body weight daily for 10 successive days, resulted in alleviation of the oxidative stress status of tamoxifen-intoxicated liver injury in rats as observed by significant increments in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases; sGPT and sGOT levels. The administration of DDB before tamoxifen intoxication (as protection) is more little effective than its curative effect against tamoxifen-induced liver injury. The data obtained from this study speculated that DDB can mediate its biochemical effects through the enhancement of the antioxidant enzyme activities and reduced glutathione level as well as decreasing lipid peroxides.

• Natural Product Sciences
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• v.14 no.2
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• pp.95-99
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• 2008

In a project to study the hepatroprotective effect of some plant extracts four plants Ephedra foliate Boiss, Alhagi maurorum Medikus, Capsella bursa-pastoris (L.) Medik. and Hibiscus sabdariffa L. were studied. The ethanol extract of the aerial part of the first three plants and the flowers of H. sabdariffa were subjected to hepatoprotective assays using Wistar albino rats. Liver injury induced in rats using carbon tetrachloride. The biochemical parameters; serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP) and total bilirubin were estimated as reflection of the liver condition. Based on the good results of the biochemical parameters measurements, histopathological study was performed on the liver of rats treated with E. foliate. The normal appearance of hepatocytes indicated a good protection of the extract from carbon tetrachloride hepatotoxicity. All the results were compared with silymarin, the reference hepatoprotective drug.

• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.572-578
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• 2006

Objectives : This study investigated whether taking herbal medicine over the long-term had any side effects of liver damage. Methods : We checked LFT levels of the 58 admitted patients. Results : When we compared admission LFT levels with discharge LFT levels, we found the levels of AST, ALT and LDH had decreased. This test showed statistically significant decrease. When we compared admission LFT levels with discharge LFT levels, we found the increases of discharge LFT levels fell within the standard deviation. When we compared admission LFT levels with discharge LFT levels, we found the levels of LFT did not increase as much as two standard deviations. Conclusions : According to the above results, taking herbal medicine over a long-term did not have any side effects of drug-induced liver damage.

• Journal of Interdisciplinary Genomics
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• v.3 no.1
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• pp.7-12
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• 2021

Adverse drug reactions (ADRs) is a hypersensitivity reactions to specific medications, and remain a common and major problem in healthcare. ADRs suchc as drug-induced liver injury and life-threatening severe cutaneous adverse drug reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms can be occurred by uncontrolled expansion of oligoclonal T cells according to genetically predisposing HLA. In this review, I summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs.

• The Journal of Korean Medicine
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• v.26 no.2 s.62
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• pp.152-165
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• 2005

Background: The use of herbal preparations as remedies for various medical conditions has continuously increased in Korea Large proportions of Korean patients use herbal medicinal products, folk remedies, and food supplements. However, studies on the safety of herbal products arc conducted on a less than sufficient basis even in the countries like Korea where herbal medicine is being used extensively. Some of the reports on the safety of herbs were done by the doctors of western medicine but lack of knowledge and misclassification led to misunderstandings. Objecitves: This study aims to review the recent evidences on hepatotoxic events associated with the use of herbal medicinal products, folk remedy, and food supplements. In the process, this review will grasp trends in this field of studies and will direct further researches into the right direction. Methods: Systematic literature searches were performed on MedRic and MEDLIS in Korea. Screening and selection of the articles and the extraction of data were performed independently by two of authors. There were no restrictions regarding the published date. In order to avoid bias, the articles written by medical doctors, not by oriental doctors were selected. 43 journals were chosen for the review. Results: Analyzing the number of journals, studies on the drug-induced liver injury were increased after the year 2000. The proportion of herbal and folk remedy associated hepatotoxic injuries in all drug-induced liver injury was $21.0\%-30.0\%$. But criterion for herbal medicine is rather vague and limited objective data hindered objectiveness. Few of single medicinal herbs and combination preparations were associated with hepatotoxic injuries. But because of lack of objectivity, further researches must be conducted to yield more concrete results. Conclusions: yield more concrete results. Incidence figures are largely unknown, and in most cases a causal attribution is not established. The challenge for the future is to systematically research this area, educate all parties involved, and minimize patient risks.

• 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 Korean Medicine Rehabilitation
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• v.32 no.3
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• pp.131-140
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• 2022

Objectives This study aimed to investigate whether the concurrent use of conventional and herbal medications affects liver and kidney function, by examining blood test data. Methods We retrospectively reviewed the electronic medical records of 590 inpatients with musculoskeletal diseases between 2013 and 2017. We investigated cases of drug-induced liver injury (DILI) according to the Roussel Uclaf Causality Assessment Method criteria and cases of drug-induced kidney injury (DIKI) based on the Kidney Disease Improving Global Outcomes definition. Results One case (0.17%) of DILI and one case (0.17%) of DIKI were identified. Significant improvements in serum laboratory data were observed after the concurrent use of both types of medications (p<0.05). The kappa coefficients ranged from 0.26 to 0.72, indicating that the values after the concurrent use of conventional and herbal medications showed a fair similarity to the baseline values of the patients. The linear regression test showed that female sex and high body mass index (BMI) were risk factors for an increase in the serum blood levels of liver function parameters. Conclusions The concurrent use of conventional and herbal medications for musculoskeletal disorders is relatively safe; however, clinicians should exercise caution when prescribing these medications to female patients and patients with a high BMI because of their potential effect on hepatic function.

• The Journal of Internal Korean Medicine
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• v.44 no.4
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• pp.635-644
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• 2023

Objectives: This study analyzed laboratory serum data results before and after patients took herbal medicine to confirm the clinical safety of herbal medicine. In addition, in the event of liver damage, the case was analyzed to confirm the characteristics of liver damage and the possibility of liver damage caused by herbal medicine. Methods: A retrospective chart review of the effects of herbal medicine on liver function in patients diagnosed with functional dyspepsia was conducted. The electronic medical records of 128 patients in a single hospital were reviewed. Results: The statistical analysis revealed a statistically significant decrease in liver function-related laboratory serum data after taking herbal medicine (p<0.05). In addition, among 128 patients, there were two cases of drug-induced liver injury (DILI) (1.56%). Conclusion: Taking herbal medicine prescribed by experts does not significantly affect liver function in patients with functional dyspepsia. Rather, the liver levels of the subjects showed a significant decrease after taking herbal medicine. To support these results, further large-scale multicenter prospective studies are necessary.