• YAKHAK HOEJI
• /
• v.59 no.5
• /
• pp.201-206
• /
• 2015

The aim of the present study was to optimize in vitro method for the prediction of drug-induced liver injury using human liver microsomes (HLM). Cytotoxicity test of cyclophosphamide and acetaminophen in HepG2 cells cultured with HLM showed that the newly established condition using 0.375 mg/ml HLM for 24 hr incubation was comparable or more sensitive than the previously established condition using 0.75 mg/ml HLM for 12 hr incubation. Although the cytotoxic effect of troglitazone was completely attenuated by 0.75 mg/ml HLM, it was augmented by 0.375 mg/ml HLM in the presence of the NADPH-generating system. The cytotoxic effect of chlormezanone, a withdrawn drug due to hepatotoxicity in human, was increased by HLM in the presence of the NADPH-generating system. In contrast, the cytotoxic effect of methapyrilene, a withdrawn drug due to hepatotoxicity in rats, was decreased by HLM in the presence of the NADPH-generating system. The present study suggests that the optimized in vitro method using HLM can be useful for the prediction of drug-induced hepatotoxicity.

• Journal of Trauma and Injury
• /
• v.35 no.1
• /
• pp.66-70
• /
• 2022

The spleen is the most commonly injured organ after blunt abdominal trauma. Nonoperative management (NOM) is the standard treatment for blunt splenic injuries in haemodynamically stable patients without peritonitis. Complications of NOM include rebleeding, new pseudoaneurysm formation, splenic abscess, and symptomatic splenic infarction. These complications hinder the NOM of patients with blunt splenic injuries. We report a case in which a large haemorrhagic fluid collection that occurred after angio-embolisation was resolved by percutaneous drainage in a patient with liver cirrhosis who experienced a blunt spleen injury.

• The Journal of Internal Korean Medicine
• /
• v.44 no.3
• /
• pp.402-417
• /
• 2023

Objective: Liver fibrosis is a highly conserved wound-healing response and the final common pathway of chronic inflammatory injury. This study aimed to evaluate the potential anti-fibrotic effect of the combination of Rhei Radix et Rhizoma water extract (RW) and silymarin in a thioacetamide (TAA)-induced liver fibrosis model. Methods: The liver fibrosis mouse model was established through the intraperitoneal injection of TAA (1 week 100 mg/kg, 2-3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg) three times per week for eight weeks. Animal experiments were conducted in five groups; Normal, Control (TAA-induced liver fibrosis mice), Sily (silymarin 50 mg/kg), RSL (RW 50 mg/kg+silymarin 50 mg/kg), and RSH (RW 100 mg/kg+silymarin 50 mg/kg). Biochemical analyses were measured in serum, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), and ammonia levels. Liver inflammatory cytokines and fibrous biomarkers were measured by Western blot analysis, and liver histopathology was evaluated through tissue staining. Results: A significant decrease in the liver function markers AST and ALT and a reduction in ammonia and total bilirubin were observed in the group treated with RSL and RSH. Measurement of reactive oxygen species and MDA revealed a significant decrease in the RSL and RSH administration group compared to the TAA induction group. The expression of extracellular matrix-related proteins, such as transforming growth factor β1, α-smooth muscle actin, and collagen type I alpha 1, was likewise significantly decreased. All drug-administered groups had increased matrix metalloproteinase-9 but a decreasing tissue inhibitor of matrix metalloproteinase-1. RSL and RSH exerted a significant upregulation of NADPH oxidase 2, p22^phox, and p47^phox, which are oxidative stress-related factors. Furthermore, pro-inflammatory proteins such as cyclooxygenase 2 and interleukin-1β were markedly suppressed through the inhibition of nuclear factor kappa B activation. Conclusions: The administration of RW and silymarin suppressed the NADPH oxidase factor protein level and showed a tendency to reduce inflammation-related enzymes. These results suggest that the combined administration of RW and silymarin improves acute liver injury induced by TAA.

• Toxicological Research
• /
• v.25 no.1
• /
• pp.29-33
• /
• 2009

Phellinus gilvus (PG) is a widely used mushroom for health promotion. We studied the hepatoprotective effect of the polysaccharide aqueous extract of PG (PGP) against carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Sprague Dawley rats were divided into 5 groups: Normal control, $CCl_4$ control, PGP 50, 100, and 200 mg/kg + $CCl_4$. The levels of serum biochemical parameters, liver lipid peroxide and antioxidant enzymes, and histological appearances were evaluated. The $CCl_4$-induced increments of alanine aminotransferase, asparate aminotransferase, and alkaline phosphatase levels in serum were significantly decreased by PGP-pretreatments. The PGP dose-dependently decreased hepatic malondialdehyde formations in $CCl_4$-treatment groups. Hepatic antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) were elevated by PGP in $CCl_4$-treatment groups. Histopathological evaluation of liver showed that the loss of hepatocytes, fatty changes, swelling and extensive necrosis of hepatocytes in centrilobular regions of the $CCl_4$-treated rats were ameliorated by PGP pretreatment. The PGP has hepatoprotective and antioxidative effects in $CCl_4$-induced liver injury of rat.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.21 no.5
• /
• pp.1081-1086
• /
• 2007

This study was performed to investigate the medicinal effects of the herbal combination extracts-2 (HCE-2), consisting of Artemisia capillaris Thunb., Lonicera japonica Thunb., Prunella vulgaris var. lilacina, and Hovenia dulcis Thunb. on the alcohol-induced liver injury in rats. The rats were randomly divided into four groups: normal group (n =6), non-treated control group (n =6), saline-treated group (n =6) and the herbal combination extract (HCE-2)-treated group (n =6). The rats in the alcohol-loaded groups were orally administered with ethanol at a daily dose of 4 g/kg-body weight for 5 weeks. Thirty minutes before the ethanol injection, saline or herbal combination extracts was administered by using a gastrogavage. Blood and liver tissue samples were taken out from the hearts and livers of the rats, respectively, on 15th and 38th days. The activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured using an enzyme-linked immunosorbent assay (ELISA). We also investigated the protective effect of the herbal combination extracts by Hematoxylin-Eosin staining on histological sections of rat liver. In this study, the oral administration of the herbal combination extracts significantly reduced the serum levels of AST and ALT, which had been raised by alcohol-induced liver injury. Histological analysis and apparent observation of liver also showed the preventive effect of the herbal combination extracts in a chronic alcohol-induced rat model. Theses results revealed that the herbal combination extracts effectively prevented hepatic damage consequent to the chronic exposure to repetitive administration of ethanol and could be used as a primary resource of a health beverage or herbal medicine, alleviating the alcohol-induced hepatic injury and hangover symptoms.

• The Korea Journal of Herbology
• /
• v.33 no.1
• /
• pp.37-46
• /
• 2018

Objectives : Liver disease is an inflammatory reaction caused by oxidative stress, viral, alcohol, and drug properties. Inflammatory reaction causes hepatitis and chronic hepatitis is persistent, it progresses to liver fibrogenesis and liver cancer. The aim of this study was to confirm the hepatoprotective effect of Tongyuhwalhyeol-tang(Tongqiaohuoxue Decoction) (TH) and Gamtongyuhawlhyeol-tang(GTH) in TAA-induced liver injury animal model. Methods : The antioxidant activities were evaluated through in vitro experiments, such as 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays, total polyphenol and total flavonoid content measurement. To confirm the liver protective effect, induced by Thioacetamide (TAA) for 3 days injection at 200 mg/kg rats. TH and GTH were treated 3 days at 200 mg/kg/day. The changes of reactive oxygen species (ROS), peroxynitrite ($ONOO^-$), alanine aminotransferanse (ALT) and aspartate aminotransferase (AST) in serum were analyzed after experiment. Also, expression of anti-inflammation, anti-oxidant related proteins were investigated by western blot analysis. Results : TH was inhibited the antioxidant activities. In the TAA-induced rat, TH decreased ROS, $ONOO^-$, ALT, AST level in serum. Inflammation related protein expressions increased in TAA-induced rat compared to normal rat. However, TH group inhibited the down expression of these proteins. Also, anti-oxidant related protein expressions increased in TH group compared TAA-induced rat. Conclusion : Therefor, these results suggested that TH provided hepatoprotective effects on the hepatic injury leading to the reduction of inflammatory response. In addition, the effect of TH was superior to that of GTH.

• Biomolecules & Therapeutics
• /
• v.13 no.3
• /
• pp.127-132
• /
• 2005

We investigated whether ischemic preconditioning (IPC) protects liver against cold ischemic injury using isolated perfused rat liver. Rat livers were preconditioned by 5 minutes of ischemia and 5 minutes of reperfusion and preserved for 30 hours at $4^{\circ}C$ in University of Wisconsin solution. Livers were then reperfused for 120 minutes. Oxygen uptake and bile flow in ischemic livers markedly decreased during reperfusion. These decreases were prevented by IPC. Portal pressure was elevated in cold ischemic and reperfused livers and this elevation was prevented by IPC. Lactate dehydrogenase and purine nucleoside phosphorylase activities markedly increased during reperfusion. These increases were prevented by IPC. The ratio of reduced glutathione to glutathione disulfide was lower in ischemic livers. This decrease was prevented by IPe. Our findings suggest that IPC protects the liver against the deleterious effect of cold ischemia/reperfusion, and this protection is associated with the reduced oxidative stress.

• Biomolecules & Therapeutics
• /
• v.5 no.1
• /
• pp.1-7
• /
• 1997

This study was done to investigate the effect of vitamin C on hypoxia/reoxygenation-induced hepatic injury ul isolated perfused rat liver. Isolated livers from rats fasted 18 hours were subjected to 45 min of hypoxia followed by reoxygenation for 45 min. The perfusion medium used was Krebs-Henseleit bicarbonate buffer (pH 7.4) and 0.5 mmol/L of vitamin C was added to the perfusate. Alanine aminotransferase (ALI) and lactate dehydrogenase (LDH) levels were significantly increased by hypoxia/reoxygenation. These increases were augmented by vitamin C. Glucose output and bile flow were markedly decreased by hypoxia/reoxygenation. Vitamin C aggavated the decrease of glucose output but had little effect on bile flow. Our findings suggest that hypoxia/reoxygenation diminishes hepatic metabolic and secretory functions, and vitamin C significantly aggravates these changes.

• Herbal Formula Science
• /
• v.10 no.2
• /
• pp.85-95
• /
• 2002

Objectives: In traditional medicine, Wolgukwhan has been used for the treatment of digestive system disease, such as indigestion, brash, ructation, nausea and vomiting. This study was purposed to investigate the effects of Wolgukwhan methnol extract (WGWM) on oxidative liver cell injury. Methods: In vivo assay, we administerated acetaminophen(500mg/kg, i.p.) to starved mice 24hrs after pretreatment of WGWM for 6days. In the liver homogenates, lipid peroxide and glutathione(GSH) levels were measured. In addition, activities of hepatic enzyme, such as catalase, glutathione peroxidase(GPX), glutathione S-transferase(GST) were measured in the hepatic mitochondrial and cytosolic fractions. Results: In vivo administeration of WGWM showed effective inhibition of acetaminophen induced lipid peroxidation and elevations of glutathione level. The acetaminophen treatment resulted in a decrease of catalase, GPX and GST activities. By contrast, WGWM pretreatment increased compare to those of untreated groups. Conclusions: These results suggested that WGWM might protect against lipid peroxidation by free radicals, destruction of hepatic cell membranes.

• The Journal of Korean Medicine
• /
• v.37 no.2
• /
• pp.119-124
• /
• 2016

Objectives: To demonstrate a clinical course and feature of a female patient with a severe liver injury (DILI) during antituberculosis treatment for her intestinal tuberculosis, whom traditional Korean medicine completely recovered. Methods: A female patient with diagnosed as DILI by antituberculosis drugs had been treated with herbal drugs; and then the clinical outcome and biochemical parameters had been monitored. Result: A 45-year old female had taken antituberculosis drugs for about 2 months, and complained severe abdominal discomfort and dyspepsia. The RUCAM score was 10, which met the criteria for DILI (AST 584 IU/L, ALT 1212 IU/L, ALP 100 IU/L, and GGT 161 IU/L, total bilirubin 0.9 mg/dL). She had been treated with herbal drugs and acupuncture as inpatient and outpatient, and then her symptoms had been completely recovered with normalization of hepatic enzymes. Conclusion: This report provides a clinical characteristic for a severe hepatotoxicity induced by antituberculosis drugs, and showed an example of TKM-based application.