• Title/Summary/Keyword: Drug-Induced Liver Disease

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The Anti-inflammatory Effects of Heat-treated Broccoli Extract (열처리된 브로콜리 추출물의 항염증 효과)

  • Kim, Hyun Kyoung
    • The Journal of the Convergence on Culture Technology
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    • v.5 no.2
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    • pp.397-404
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    • 2019
  • This study was carried out to investigate the heat-treated broccoli extraction which have a beneficial effect on the human body and which can be used safely for a long period of time without adverse side effects and also have excellent effects of protecting liver and improving liver function. The heat-treated broccoli extract does not show cytotoxicity, and thus can be used safely. In an experiment performed on an animal model with liver injury induced by a drug (APAP), it could be seen that the heat-treated cabbage extract exhibited the effects of protecting liver and improving liver function by effectively reducing AST and ALT which are liver injury markers, indicating that the heat-treated brocoli extract is effective as a pharmaceutical extraction for preventing or treating liver disease. In particular, the heat-treated broccoli extract was effective in treating inflammation of the liver by reducing the expression of the inflammatory mediators iNOS and COX-2 and the proinflammatory cytokine $IL-1{\beta}$, which are involved in acute inflammatory reactions accompanying liver injury.

The effect of Gagamchunggan-tang on lipopolysaccharide-induced expression of $NF{\kappa}-B$ downstream genes in HepG2 cell (Lipopolysaccharide로 유발된 HepG2 세포의 염증반응에 대한 가감청간탕의 효과에 대한 연구)

  • Kim Sung-Hwan;Seo Sang-Ho;Hong Sang-Hoon
    • The Journal of Internal Korean Medicine
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    • v.24 no.1
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    • pp.113-122
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    • 2003
  • Objective : The aim of this study was to evaluate the efficacy of Gagamchunggan-tang on anti-inflammation reaction with lipopolysaccharide (LPS)-induced HepG2 cell. Method : We examined the effects of the Gagamchunggan-tang, a traditional drug for liver inflammation, on the process of lipopolysaccharide(LPS)-induced nuclear factor-${\kappa}Bp65(NF-{\kappa}Bp65)$ activation in HepG2 cell. SDS-PAGE, Western blotting, Immunofluorescence staining were studied. Results : Immunoblot analysis showed that the level of nucleic $NF-{\kappa}Bp65$ was rapidly up-regulated and cytosolic inhibitory $I-{\kappa}B{\alpha}$ was down-regulated by LPS challenge. While Gagamchunggan-tang inhibited an increase of $NF-{\kappa}Bp65$ and degradation of $I-{\kappa}B{\alpha}$ in HepG2 cell. Besides LPS-induced expression of a group of genes, such as tumor necrosis factor-${\alpha}(TNF-{\alpha})$, inducible nitric oxide synthase(iNOS) and cyclooxygenase-2 (COX-2), are repressed by Gagamchunggan-tang. It may be concluded that Gagamchunggan-tang attenuates the progress of LPS-induced inflammation by reduction of $NF-{\kappa}Bp65$ activation. Conclusion : The Gagamchunggan-tang would be useful as a therapeutic agent for endotoxin-induced liver disease.

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Measurement of CYP450 Enzymes Activity of Bosentan in HepaRG Cell (HepaRG 세포를 이용한 Bosentan 약물의 CYP450 효소활성 측정)

  • Han, Kyoung-Moon;Jung, Jung-A;Sin, Ji-Soon;Cha, Hye-Jin;Bae, Young-Ji;Kim, Hyun-Uk;Kim, Young-Hoon;Seong, Won-Keun;Kang, Hoil
    • YAKHAK HOEJI
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    • v.58 no.4
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    • pp.255-261
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    • 2014
  • Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metabolism happens in the liver by CYP isozymes and the metabolism by CYP450 enzymes. The Cytochrome P450 (CYP) is a superfamily of enzymes that catalyzes the oxidations of many endogenous and exogenous compounds. Primary human Hepatocytes (HH) are considered as the gold standard model for In vitro drug interaction studies. However, there are several limitations (cost, limited life span) for using HH cells. HepaRG cells are being used as a possible alternative. HepaRG cells were cultured in William E medium containing the positive control inducers (1A2: 10, 25, 50 ${\mu}M$ omeprazole, 2C9 and 2C19: 10 ${\mu}M$ rifampin, 3A4: 10, 25, 50 ${\mu}M$ rifampin) at $37^{\circ}C$, 5 % $CO_2$ in a humidified atmosphere. This study was to evaluate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction ability of Bosentan, as a drug of pulmonary artery hypertension, in HepaRG cells. For reference, dose of the Bosentan is determined to the basis of the $C_{max}$ (835 mg/ml) value. The enzyme activity demonstrated that CYP2C9 and 3A4 were induced up to 20 times by Bosentan. Like as In vivo, the enzyme activity of CYP2C9 and CYP3A4 is significantly induced in a dose-dependent by Bosentan.

A Review on the Report about Drug-induced Hepatitis published by the National Institute of Toxicological Research (국립독성연구원 보고서 '식이유래 독성간염의 진단 및 보고체계 구축을 위한 다기관 예비연구'에 대한 분석 및 고찰)

  • Jang Insoo
    • The Journal of Korean Medicine
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    • v.25 no.3
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    • pp.78-89
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    • 2004
  • Background : A report published by the National Institute of Toxicological Research (NITR) in January 2004 about toxic hepatitis in Korea contained the result of analysis on 55 cases of severe toxic hepatitis from 7 university hospitals for 8 months. NITR claimed that the extrapolated annual frequency of severe toxic hepatitis in Korea was 1904 cases per year. They also claimed that the most frequent etiology of severe toxic hepatitis were herbal medications and similar plant preparations (61.7%), contrasted with traditional therapeutic preparations and healthy foods (29.1%). I have investigated that report to be certain of the result because it is a very important subject for public health and society in Korea. Results : The NITR report has too many problems to have faith in its results. They include the following: 1. The report uses only 55 cases to estimate annual prevalence rate of severe toxic hepatitis in Korea. 2. There was a large regional preponderancy in the NITR report (2 cases in Seoul from a population of 10.17 million, 19 cases in Gwangju from a population of 1.4 million) 3. There was another preponderancy that selected much fewer cases caused by western medication (9.1%) than other reasons. 4. The NITR report used a modified scale than that officially recognized to diagnose toxic hepatitis. 5. There was a mistake using the scale to adapt the right indications. 6. They collected cases before beginning the study, although it was a prospective study. There was also not any questionnaire or other materials concerned with alcohol, drugs, or history of past liver disease. Conclusions : NITR is one of the important official arms of the government of Korea. Nevertheless, there is a severe problem in validity because of selection bias, uncertain accuracy, and insufficiency of raw materials in the report. Therefore it seems incorrect to generalize the results of the report and there is a lack of confidence in it as a national study publishing by the NITR.

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Hepatoprotective and Antioxidative Effects of Alisma orientale

  • Rhew, Kwang-Yul;Choi, Hyuck-Jai;Kim, Nam-Jae;Lee, Jang-Hoon
    • Natural Product Sciences
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    • v.17 no.4
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    • pp.285-290
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    • 2011
  • The rhizome of Alisma orientale Juzep (Alismataceae) has been used as a crude drug for diabetes, edema, inflammation and urinary disturbances in oriental medicine. Recent animal studies have shown that the extract of Alisma orientale rhizome (AOR) can potently lower high levels of serum lipids and improve insulin resistance, which are usually detected in patients and animals with non-alcoholic fatty liver disease. So, we studied the antioxidative effects of AOR extracts and fraction in vitro and their protective effects against acute hepatotoxicity induced by $CCl_4$ in vivo.. We then investigated the effects of each fraction on hepatotoxicity induced by tert-butyl hydroperoxide (t-BHP). DAOR (dichloromethane fraction of the Alisma orientale rhizome) scavenged free radicals and superoxide anions. DAOR protected against $CCl_4$ induced hepatotoxicity. DAOR had hepatoprotective and antioxidative effects against t-BHP-induced hepatotoxicity in HepG2 cells and in rats.

The Effect of Chunggan Plus Extract in Improving Liver Function: A Retrospective Case Series of Eight Patients (청간플러스의 간기능 개선 효과 : 후향적 증례보고 8례)

  • Lee, Ga-young;Park, Chan-ran;Cho, Jung-hyo;Son, Chang-gue;Lee, Nam-hun
    • The Journal of Internal Korean Medicine
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    • v.41 no.3
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    • pp.542-551
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    • 2020
  • Objectives: The purpose of this study was to retrospectively assess the effectiveness of Chunggan plus extract (CGX) in improving liver function in a Korean medical clinic. Methods: We collected the data of inpatients who received CGX to improve abnormal liver function test (LFT) results from March 2016 to February 2020. We analyzed the changes in LFT and adverse events based on subjective symptom changes and creatinine results. Results: The data of eight patients, three male and five female, were selected by inclusion criteria (patients who did LFT before and after the prescription of CGX and who prescribed CGX more than 6 days) and exclusion criteria (patients who administered other herbal medicine for improving liver function except CGX and who are diagnosed with terminal stage of hepatobiliary cancer). As a cause of abnormal LFT, one case was diagnosed with alcoholic liver disease, two cases with non-alcoholic fatty hepatitis, and one case with cholecystitis. Three of the other four were suspected to have drug-induced hepatitis, and one case was determined to have an unknown cause. Most patients showed a decrease in LFT results (Aspartate transaminase 87.5%, Alanine transaminase 87.5%, and Alkaline Phosphatase 100%) without any critical adverse events. Conclusions: CGX may be an efficient and convenient herbal medicine for improving liver function regardless of the chief impression. Further study should be conducted to evaluate the effectiveness of CGX.

Drug research and development tend to hyperlipidemia (이상지질혈증과 치료제 연구개발 경향)

  • Seol, In-Chan
    • Journal of Haehwa Medicine
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    • v.18 no.2
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    • pp.1-12
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    • 2009
  • Most of the cholesterol is synthesized by liver in the body while about one of third is taken via dietary. The main functions of cholesterol is to protect membranes in cell surface, avoid the arterial bleeding by hypertension, and prolong the life of erythrocytes, and so on. However, overload of cholesterol leads to arteriosclerosis associated with leading death cause. Lack of physical activity, emotional and environmental stress, and low intake of protein or vitamin E induce the unbalance between HDL- and LDL-cholesterol so become a basis of ischemic disorders in heart, brain and elsewhere in the body. So far, four major classes of medications for hyperlipidemia are HMG-CoA reductase inhibitors (statins), bile acid sequestrants, nicotinic acid, and fibric acids. The statins can lower LDL and levels triglyceride, but may induce myopathy and an elevation of liver enzyme levels. The bile acid sequestrants lower LDL levels and raise HDL levels with no effect on triglyceride levels but side effects of gastrointestinal (GI) distress, constipation, and a decrease in the absorption of other drugs. Nicotinic acid and fibric acids lower LDL and triglyceride levels with showing flushing, hyperglycemia, hyperuricemia, GI distress, and hepatotoxicity dyspepsia, gallstones, myopathy, and unexplained noncardiac death as adverse effects. Above western drugs lower cholesterol by 15 to 30% while all have notable adverse effects. In traditional medicine, hyperlipidemia is regarded as retention of phlegm and fluid disease. Etiology and pathogenesis of hyperlipidemia is basically based on Spleen-Deficiency and Phlegm-Stagnation, accumulation and stasis of -heat, and Qi & blood stagnation induced by Phlegm-damp, water-dampness, and blood stasis. Thereby, strengthening Spleen and dissolving Phlegm, clearing away heat and diuresis, and supplementing Qi and activating blood circulation are commonly used therapeutic methods for hyperlipidemia. The traditional herbal medicine, have been used for patients with CVA, hypertension or hyperlipidemia in Oriental hospital or Oriental clinic. The lock and key theory is used to develop most of western medicine, however many diseases are caused by mixed factors in body-complex system. We expect that Oriental pharmacological theory could be newborn as a novel drug showing high advantage of blood levels of lipidsand QOL of performance without side effects.

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Antioxidative Effects of Scutellariae Radix Aaquaacupuncture Solution on Lipid Peroxidation Induced by Free Radicals (자유기에 의한 지질과산화 반응에 대한 황금 약침액의 항산화 효능)

  • Kim Sung-Il;Moon Jin-Young;Kim Kap-Sung;Kim Doo-Hie;Nam Kyung-Soo;Lim Jong-Kook
    • Journal of Society of Preventive Korean Medicine
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    • v.1 no.1
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    • pp.48-54
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    • 1997
  • Scutellariae radix, has been used as a natural drug for fever, inflammation, cataract, and liver disease in traditional medicine. This study was performed in order to investigate the antioxidative effects of Scutellariae radix aqua-acupuncture solution (SRAS) on lipid peroxidation by free radicals. Lipid peroxidation levels were determined by TBA method during the autoxidation of linoleic acid. In this linoleic acid autoxidation system, SRAS markedly exhibited antioxidant activity, which inhibited 89% of linoleic acid peroxidation. SRAS showed scavenging effects on ${\alpha},{\alpha}-diphenyl-{\beta}-picrylhydrazyl$(DPPH) radical, inhibited superoxide generation in xanthine-xathine oxidase system, and also inhibited lipid peroxidation of rat liver tissue by hydroxyl radical derived from $H_2O_2-FE^{+2}$ system. These effects were similar to those of $dl-{\alpha}-tocopherol$, BHA and BHT. In addition, SRAS protected the cell death induced by ter-butyl hydroperoxide (t-BHP) and significantly increased cell viability in the normal rat liver cell (Ac2F). On the basis of these results, it is suggested that SRAS might play a protective role in lipid peroxidation by free radicals.

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Effects of Oldenlandiae Diffusae Herba Methanol Extract on Acetaminophen Induced Acute Liver Injury in Mice (백화사설초 메탄올 추출물이 acetaminophen으로 유도된 생쥐의 급성 간손상에 대한 효능 연구)

  • Kim, Jong-Dae;Moon, Jin-Young
    • Herbal Formula Science
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    • v.9 no.1
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    • pp.355-366
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    • 2001
  • Objectives : Oldenlandiae Diffusae herba has been used as a natural drug for tumor, inflammation and liver disease in traditional medicine. This study was performed in order to investigate the antioxidative effects of Oldenlandiae Diffusae herba methanol extract(ODHM) on acetaminophen induced acute liver injury in mice. Methods : In order to investigate the protective effect of ODHM on acute hepatic injury in vivo, ICR mice were pretreated with ODHM, and then treated with acetaminophen(500mg/kg). And the levels of LPO and glutathione(GSH), antioxidative enzyme activities were measured. The levels of LPO were measured by TBA method. And catalase activity was measured as the decrease in hydrogen peroxide absorbance at 240nm on spectrophotometer using 30mM hydrogen peroxide. Superoxide dismutase(SOD) was assayed by recording the inhibition of nitro blue tetrazolium reduction with xanthine and xanthine oxidase. Glutathione peroxidase(GPX) activity was determined by the modified coupled assay developed by Paglia and Lawrence. The reaction was started by addition of 2.2mM hydrogen peroxide as substrate. The change in absorbance at 340nm was measured for 1min on spectrophotometer. Glutathione-S-transferase(GST) activity was assayed with CDNB as substrate and enzyme activity of GST towards the glutathione conjugation of CDNB. And Total SH and GSH levels were measured. Results : In vivo study, LPO levels of acetaminophen treatment group were significantly higher than other groups. This increased level was significantly reduced by ODHM pretreatment. The acetaminophen treatment resulted in a decrease of catalase, GPX, SOD and GST activities. By contrast, ODHM pretreatment markedly increased compare to those of untreated groups. Total SH and GSH levels were reduced by of acetaminophen treatment, and ODHM pretreatment significantly increased GSH levels.

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A comparison of metabolomic changes in type-1 diabetic C57BL/6N mice originating from different sources

  • Lee, Seunghyun;Kwak, Jae-Hwan;Kim, Sou Hyun;Yun, Jieun;Cho, Joon-Yong;Kim, Kilsoo;Hwang, Daeyeon;Jung, Young-Suk
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.232-238
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    • 2018
  • Animal models have been used to elucidate the pathophysiology of varying diseases and to provide insight into potential targets for therapeutic intervention. Although alternatives to animal testing have been proposed to help overcome potential drawbacks related to animal experiments and avoid ethical issues, their use remains vital for the testing of new drug candidates and to identify the most effective strategies for therapeutic intervention. Particularly, the study of metabolic diseases requires the use of animal models to monitor whole-body physiology. In line with this, the National Institute of Food and Drug Safety Evaluation (NIFDS) in Korea has established their own animal strains to help evaluate both efficacy and safety during new drug development. The objective of this study was to characterize the response of C57BL/6NKorl mice from the NIFDS compared with that of other mice originating from the USA and Japan in a chemical-induced diabetic condition. Multiple low-dose treatments with streptozotocin were used to generate a type-1 diabetic animal model which is closely linked to the known clinical pathology of this disease. There were no significantly different responses observed between the varying streptozotocin-induced type-1 diabetic models tested in this study. When comparing control and diabetic mice, increases in liver weight and disturbances in serum amino acids levels of diabetic mice were most remarkable. Although the relationship between type-1 diabetes and BCAA has not been elucidated in this study, the results, which reveal a characteristic increase in diabetic mice of all origins are considered worthy of further study.