• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.218-223
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• 2018

The liver is an essential organ for the detoxification of exogenous xenobiotics, drugs and toxic substances. The incidence rate of non-alcoholic liver injury increases due to dietary habit change and drug use increase. Our previous study demonstrated that Ecklonia stolonifera (ES) formulation has hepatoprotective effect against alcohol-induced liver injury in rat and tacrine-induced hepatotoxicity in HepG2 cells. This present study was designated to elucidate hepatoprotective effects of ES formulation against carbon tetrachloride ($CCl_4$)-induced liver injury in Sprague Dawley rat. Sixty rats were randomly divided into six groups. The rats were treated orally with ES formulation and silymarin (served as positive control, only 100 mg/kg/day) at a dose of 50, 100, or 200 mg/kg/day for 21 days. Seven days after treatment, liver injury was induced by intraperitoneal injection of $CCl_4$ (1.5 ml/kg, twice a week for 14 days). The administration of $CCl_4$ exhibited significant elevation of hepatic enzymes (like AST and ALT), and decrease of antioxidant related enzymes (superoxide dismutase, glutathione peroxidase and catalase) and glutathione. Then, it leaded to DNA damages (8-oxo-2'-deoxyguanosine) and lipid peroxidation (malondialdehyde). Administration of ES formulation inhibited imbalance of above factors compared to $CCl_4$ induced rat in a dose dependent manner. Real time PCR analysis indicates that CYP2E1 was upregulated in $CCl_4$ induced rat. However, increased gene expression was compromised by ES formulation treatment. These findings suggests that ES formulation could protect hepatotoxicity caused by $CCl_4$ via two pathways: elevation of antioxidant enzymes and normalization of CYP2E1 enzyme.

• The Journal of Korean Medicine
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• v.24 no.3
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• pp.96-107
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• 2003

Objective : This study was undertaken to determine if Pyunggangaeuljihyul-tang (Pinggankaiyuzhixue-tang, PG) has a protective effect against cell injury induced by various toxic agents in rabbit liver, Methods : Cell injury in vitro was estimated by measuring lactate dehydrogenase (LDH), and that in vivo was estimated by measuring alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in serum. Lipid peroxidation was examined by measuring malondialdehyde, a product of lipid per oxidation. Results : PG prevented the LDH release by $CCl_4$, mercury, menadione, and tert-butyl hydroperoxide treatment in vitro in liver slices. The extent of protection by 2% PG was similar to that of $10{\mu\textrm{M}}$ N,N'-diphenyl-p-phenylenedianline, a potent antioxidant, in tert-butyl hydroperoxide-induced LDH release. PG also prevented lipid peroxidation and depletion of cellular ATP induced by Hg. Hg causes motphological changes including cell necrosis and its effect was significantly prevented by PG. When rats were treated intraperitoneatly with 0.5 ml/kg of $CCl_4$, serum alanine aminotransferase and aspartate aminotransferase activities were increased compared with the control, which was significantly inhibited by pretreatment of PG. PG also prevented reduction in GSH and lipid peroxidation induced by $CCl_4$ Conclusion : These results suggest that PG exerts aprotective effect against various toxic agents by its antioxidant action in liver tissues. Thus, PG may be used in prevention and treatment of drug-induced liver cell injury. However, the precise mechanisms of PG protection remain to be determined.

• Journal of Haehwa Medicine
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• v.18 no.1
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• pp.83-88
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• 2009

Recently, herbal drugs haver been used world wide. and generally regarded as safe with no serious adverse reaction. Drug-induced liver injury (DILI) is one of frequent cause of liver diseases. If DILI is not treated, it can be developed into liver cirrhosis, hepatoma, etc. Currently, DILI has been reported to be common cause of acute hepatitis, and oriental medicine and folk remedy are not exception. We encountered one case of DILI, cause by folk remedy. Patients complained chest discomfort, yellow skin and urine, nausea, vomiting. Lab test showed elevated level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (r-GTP), total bilirubin (TB). We estimated acute DILI and stopped taking folk medication made by himself. After 1 week of treatment, the clinical symptoms and liver function improved. Genetic and environmental factors as well as drug itself decide the hepatic toxicity, and the major DILI are belonged in acute type. So we need to get more attention to folk medication to help preventing the DILI cause by folk remedy.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.15 no.2
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• pp.111-116
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• 2012

Toxic hepatitis is a rare but devastating disease in children. Herbs are widely used in oriental medicine to treat various symptoms in Korea, however, several herbs have been reported to induce liver injury. We report a case of toxic hepatitis induced by Hovenia dulcis in a 3-year-old boy. He complained of nausea, abdominal discomfort, and jaundice. The patient had consumed water boiled with hovenia dulcis for about 1 year prior to presentation. A diagnosis of toxic hepatitis was made based on his history, laboratory data, viral markers, ultrasonography, and biopsied liver tissue. We administered supportive management for acute fulminant hepatitis but his symptoms and liver function progressed. He was transferred to another hospital for further evaluation and consideration for liver transplantation. Because acute liver failure due to herbs or dietary supplement taken for a long time is often fetal, it is important to make early diagnosis and stop taking the drug as soon as drug induced liver injury is suspected.

• The Journal of Internal Korean Medicine
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• v.34 no.2
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• pp.192-203
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• 2013

Objectives : To investigate the incidence of drug-induced liver injury (DILI) by combined-prescription of Korean herbal medicine (KHM; prescribed herbal medicine by doctors of traditional Korean medicine) and Western medicine on liver function. Methods : Sixty-nine in-patients who took KHM and Western medicine for various conditions were enrolled for prospective observational study. All subjects were given liver and renal function tests at the start of hospitalization to establish a baseline. After taking KHM and Western medicine, tests were done at approximately 4-week intervals afterwards. Results : Fifty-three subjects showed normal liver function test (LFT) at baseline, 50 subjects (72.5%) remained within the normal range at the second test, while 3 subjects (4.3%) tests revealed slight increase of LFT. However not a single patient had a high enough raised LFT to indicate liver injury. Sixteen of 69 subjects had abnormal baseline, 11 subjects recovered to normal levels and 5 subjects remained at abnormal level. Among all subjects, there was no statistically significant increase in LFT level between the first and second tests. Conclusions : This study shows that the combined-prescription of KHM and Western medicine did not cause any DILI. In some cases, combined treatment increased LFT levels but those increases were not high enough to have statistical significance. Additional large scale and systematical studies are required for more conclusive proof and results.

• 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.

• Herbal Formula Science
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• v.11 no.2
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• pp.135-146
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• 2003

Objectives : Wolguk-whan has been used as a prescription of natural drug for the treatment of stress digestive system disease. Recently, we reported that Wolguk-whan methnol extract (WGWM) exerted a significant protective effect against oxidative damage to the liver of ICR mice. This study was purposed to investigate the effects of Wolguk-whan water extract (WGWW) on liver injury induced by oxidative stress. Methods : In order to investigate the effects of WGWW on acute liver injury, ICR mice were pretreated with WGWW for 6days, starved for 24hrs, and administerated acetamirtophen(500mg/kg, i.p.). In the liver homogenates, lipid peroxide and glutathione(GSH) levels were measured. In addition, activities of hepatic enzyme, such as catalase, glutathione peroxidase(GSH-Px), glutathione S-transferase(GST) were measured in the hepatic mitochondrial and cytosolic fractions. Results : In vivo administeration of WGWW showed effective inhibition of acetaminophen induced lipid peroxidation, and showed elevations of GSH level, catalase, GSH-Px, GST activities. Conclusions : These results suggested that WGWW might suppress the formation of oxidative metabolites, and prevent acetaminophen induced hepatotoxicity.

• International Journal of Internet, Broadcasting and Communication
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• v.12 no.3
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• pp.131-138
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• 2020

The cabbage extract of the research 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 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 cabbage extract is effective as a pharmaceutical composition for preventing or treating liver disease. In particular, the cabbage 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-1β, which are involved in acute inflammatory reactions accompanying liver injury. In the research, an extract of cabbage heat-treated at a temperature of 100 to 150℃ had a better liver function-improving effect or anti-inflammatory effect than an extract of raw cabbage.

• The Journal of Internal Korean Medicine
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• v.36 no.1
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• pp.69-75
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• 2015

Objectives : To investigate the clinical features of drug-induced liver injury (DILI) and traditional Korean medicine (TKM) -based management. Methods : A female patient diagnosed with DILI caused by Western drugs had been treated with Oriental therapies, then the subjective clinical outcome and biochemical parameters were monitored. Results : A 73-year-old female had taken Western drugs (nonsteroidal anti-inflammatory and skeletal muscle relaxants) for about 3 months, and complained of severe abdominal discomfort and tiredness. Her RUCAM score was 9, which met the criteria for DILI (AST 90 IU/L, ALT 100 IU/L, ALP 191 IU/L, and GGT 614 IU/L). She was treated with herbal drugs, moxibustion, and acupuncture, and her symptoms completely resolved, with normalized hepatic enzymes within two weeks. Conclusions : This case report provides a clinical characteristic for a typical DILI caused by Western medicine, and shows an example of a TKM-based application.

• The Korea Journal of Herbology
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• v.33 no.1
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• pp.9-15
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• 2018

Objectives : The root bark of Dictamnus dasycarpus has been frequently used to treat patients with skin diseases in Korea. Recently, wild root of D. dasycarpus are reported to induce liver injury. Methods : Traditional uses of D. dasycarpus for skin diseases were analysed bibliographically. In addition, reported cases were collected and analysed using pubmed and national digital library. Results : In taiwan, D. dasycarpus revealed to be one of major herbs for skin diseases and many researchers in worldwide had reported its dermatological efficacies. Reported cases related in liver injury described that hepatocellular or cholestatic liver injury were seen in patients eating wild root of D. dasycarpus. In addition, 6 cases in worldwide and 1 case in Korea showed that patients with drug induced liver injury (DILI) ingested not root bark of D. dasycarpus but prescriptions containing root bark of D. dasycarpus. These mean that wild root of D. dasycarpus (Bongsam or Bongwhangsam) was estimated to be closely related in DILI. Whereas, it was difficult to confirm direct correlation between root bark of D. dasycarpus used as herbal medicine by doctor of Korean medicine and DILI. Conclusions : these results imply that wild root of D. dasycarpus is closely related in DILI and strong recommendation not to take it without consultation by experts is needed. In addition, although there are no evidences of direct correlation between root bark of D. dasycarpus and DILI, doctor of Korean medicines should pay attention to use root bark of D. dasycarpus in their clinics.