• Title/Summary/Keyword: Acute liver injury

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Metformin ameliorates bile duct ligation-induced acute hepatic injury via regulation of ER stress

  • Lee, Chi-Ho;Han, Jung-Hwa;Kim, Sujin;Lee, Heejung;Kim, Suji;Nam, Dae-Hwan;Cho, Du-Hyong;Woo, Chang-Hoon
    • BMB Reports
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    • v.53 no.6
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    • pp.311-316
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    • 2020
  • Cholestasis is a condition in which the bile duct becomes narrowed or clogged by a variety of factors and bile acid is not released smoothly. Bile acid-induced liver injury is facilitated by necrotic cell death, neutrophil infiltration, and inflammation. Metformin, the first-line treatment for type 2 diabetes, is known to reduce not only blood glucose but also inflammatory responses. In this study, we investigated the effects of metformin on liver injury caused by cholestasis with bile acid-induced hepatocyte injury. Static bile acid-induced liver injury is thought to be related to endoplasmic reticulum (ER) stress, inflammatory response, and chemokine expression. Metformin treatment reduced liver injury caused by bile acid, and it suppressed ER stress, inflammation, chemokine expression, and neutrophil infiltration. Similar results were obtained in mouse primary hepatocytes exposed to bile acid. Hepatocytes treated with tauroursodeoxycholic acid, an ER stress inhibitor, showed inhibition of ER stress, as well as reduced levels of inflammation and cell death. These results suggest that metformin may protect against liver injury by suppressing ER stress and inflammation and reducing chemokine expression.

Delayed Splenic Rupture Following Minor Trauma in a Patient with Underlying Liver Cirrhosis (간경화증 환자에서 경도 외상 후 발생한 지연 비장 파열)

  • Jeung, Kyung-Woon;Lee, Byung-Kook;Ryu, Hyun-Ho
    • Journal of Trauma and Injury
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    • v.24 no.1
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    • pp.52-55
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    • 2011
  • The spleen is the most frequently injured organ following blunt abdominal trauma. However, delayed splenic rupture is rare. As the technical improvement of computed tomography has proceeded, the diagnosis of splenic injury has become easier than before. However, the diagnosis of delayed splenic rupture could be challenging if the trauma is minor and remote. We present a case of delayed splenic rupture in a patient with underlying liver cirrhosis. A 42-year-old male visited our emergency department with pain in the lower left chest following minor blunt trauma. Initial physical exam and abdominal sonography revealed only liver cirrhosis without traumatic injury. On the sixth day after trauma, he complained of abdominal pain and diarrhea after eating snacks. The patient was misdiagnosed as having acute gastroenteritis until he presented with symptoms of shock. Abdominal sonography and computed tomography revealed the splenic rupture. The patient underwent a splenectomy and then underwent a second operation due to postoperative bleeding 20 hours after the first operation. The patient was discharged uneventfully 30 days after trauma. In the present case, the thrombocytopenia and splenomegaly due to liver cirrhosis are suspected of being risk factors for the development of delayed splenic rupture. The physician should keep in mind the possibility of delayed splenic rupture following blunt abdominal or chest trauma.

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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Protective effects of four types of Taraxaci Herba water extract on carbon tetrachloride-induced acute liver injuries in mice (사염화탄소 유도성 급성 간 손상 모델에서 포공영(蒲公英) 열수 추출물 4종의 간 보호 효능 연구)

  • Choi, Beom-Rak;Cho, Il Je;Jung, Su-Jin;Kim, Jae Kwang;Lee, Dae Geon;Ku, Sae Kwang;Park, Ki-Moon
    • Herbal Formula Science
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    • v.28 no.1
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    • pp.1-13
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    • 2020
  • Objectives : Present study investigated hepatoprotective effects of four types of Taraxaci Herba water extract (TL-F, Taraxaci Herba leaf originated from foreign country; TR-F, Taraxaci Herba root originated from foreign country; TL-K, Taraxaci Herba leaf originated from Korea; TR-K, Taraxaci Herba root originated from Korea) on carbon tetrachloride (CCl4)-induced acute liver injury. Methods : Mice were administered orally with 200 mg/kg of TL-F, TR-F, TL-K, or TR-K for seven days, and intraperitoneally injected with 0.5 mL/kg of CCl4 1 h after last Taraxaci Herba treatment. Silymarin (100 mg/kg) was used as a positive drug. Body weight gain, relative liver weight, serum biochemistry, histopathological and immunohistochemical analyses, and hepatic antioxidant capacity were determined to investigate the hepatoprotective effect of four extracts. Results : Administration of four types of Taraxaci Herba extract increased body weight gain, and decreased relative liver weight in CCl4-injected mice. As compared to CCl4 group, TL-F and TR-F significantly decreased serum aspartate aminotransferase activity, while four extracts reduced CCl4-induced alanine aminotransferase activity. In addition, TL-F and TR-F significantly decreased the numbers of degenerated hepatocytes, infiltrated inflammatory cells, cleaved caspase-3 positive cells, and cleaved PARP positive cells in hepatic tissues. Moreover, TL-F, TR-F, and TR-K administration reduced the lipid peroxidation and nitrotyrosine, and increased glutathione, superoxide dismutase, and catalase activities in hepatic tissues. There were no statistical differences between TL-F- and silymarin-treated group. Conclusion : Of four extracts tested, present results suggest that TL-F is the most favorable candidate against CCl4-induced acute liver injury through enhancing antioxidant activity.

Hepatoprotective effect of fermented Schizandrae Fructus Pomace extract and Hoveniae Semen Cum Fructus extract combination mixtures against carbon tetrachloride-induced acute liver injured mice (사염화탄소 유발 급성 간 손상에 대한 발효 오미자박 및 헛개과병 추출물의 혼합 비율에 따른 간 보호효능)

  • Hye-Rim, Park;Kyung Hwan, Jegal;Beom-Rak, Choi;Jae Kwang, Kim;Sae Kwang, Ku
    • Herbal Formula Science
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    • v.31 no.1
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    • pp.53-65
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    • 2023
  • Objectives : Present study investigated the hepatoprotective effects and the optimal mixing ratio of fermented Schizandrae Fructus Pomace (fSFP) and Hoveniae Semen Cum Fructus (HSCF) extract combination in carbon tetrachloride (CCl4)-induced acute liver injury mice. Methods : ICR mice were orally administered with 200 mg/kg of fSFP, HSCF and mixtures of fSFP and HSCF [MSH (w:w); 1:1, 1:2, 1:4, 1:6, 2:1, 4:1, 6:1, and 8:1] for 7 consecutive days. Silymarin (100 mg/kg) was administered as a reference drug. 0.5 mL/kg of CCl4 was injected intraperitoneally to induce acute liver injury. Body weight gain, relative liver weight, serum chemistry, histopathological analysis, and hepatic endogenous antioxidants capacities were observed. Results : All diverse combinations of MSH significantly reduced relative liver weight increase by CCl4. In addition, MSH administrations significantly decreased the elevation of serum alanine aminotransferase and aspartate aminotransferase activities by CCl4. Histopathological observation indicated that all MSH treatments significantly reduced the increase of degenerated hepatocytes, inflammatory cell infiltration, and histological activity index score by CCl4. Moreover, all MSH administrations reduced the elevation of malondialdehyde contents, and ameliorated the reduction of hepatic glutathione contents, superoxide dismutase activity, and catalase activity. Among the various mixing ratio of MSH combinations, MSH 1:1 and 2:1 showed the most potent anti-oxidative stress, and hepatoprotective effect. Conclusion : Present results suggest that 1:1 and 2:1 combinations of MSH is promising herbal formulation with the hepatoprotective effect against oxidative stress.

The Toxicity of Fthalide in Rats (흰쥐에 있어서 Fthalide의 독성)

  • 김영찬;장영수
    • YAKHAK HOEJI
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    • v.39 no.4
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    • pp.450-460
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    • 1995
  • The acute toxicity of fthalide in rat was studied in vivo by the observations of the changes in hematogram, serological parameters, content of cytochrome p-450, activities of NADPH-cytochrom c reductase, glucose-6-phosphatase, and the contents of cholinesterase and carboxylesterase in liver. Fthabde is a practically non-toxic substance(LD50 is 3.86g/kg), but rats were intoxicated with fthabde at a oral dose of 100 mg/kg for 12 days. WBC were significantly decreased and activities of ALT and LDH, on the cotrary, the content of glucose in serum were slightly increased. Cytochrome p-450 and lipid peroxide in liver were significantly increased in the fthalide-intoxicated rats. The longer administration of fthalide showed further increase of carboxylesterase activity in liver and serum, but decrease of activities of glucose-6-phosphatase and cholinesterase in liver and serum. These results show that fthatide can induce the hepatocellular injury and neurotoxicity.

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The Effects of Protecting Liver and Improving Liver Function on Cabbage Extract (양배추 추출물의 간보호 및 간기능 개선 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.389-395
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    • 2019
  • This study investigated the pharmaceutical extraction and the functional health food 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. As the results, the cabbage 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 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 extraction 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 $IL-1{\beta}$, which are involved in acute inflammatory reactions accompanying liver injury. In the results, an extract of cabbage heat-treated at a temperature of 100 to $150^{\circ}C$ had a better liver function-improving effect or anti-inflammatory effect than an extract of raw cabbage.

Protective Effect of Lithospermum erythrorhizon on Galactosamine Induced Liver Injury (자초(Lithospermum erythrorhizon)추출물의 투여가 Galactosamine으로 유도된 간손상에 미치는 보호 효과)

  • Lee, Hyun-Hwa;Yoon, Jung-Sik;Song, Seon-Young
    • Applied Microscopy
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    • v.40 no.1
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    • pp.29-35
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    • 2010
  • The present study was carried out to investigate the hepatoprotective effect of water extract of Lithospermum erythrorhizon on acute hepatotoxicity induced in Sprague-Dawley (SD) rats by a single dose of galactosamine (400 mg/kg, i.p). The animals were divided into four groups. The animals in the Con group were fed basal diet. GalN group were administered with galactosamine. LE200 and LE500 groups treated with water extract of Lithospermum erythrorhizon (such as 200 and 500 mg/kg/day, p.o) for 7 days before galactosamine injection. In the change of AST, ALT, ALP, GGT and LDH contents, as compared with GalN group, LE200 group were significantly decreased. According to the electron microscopical observation, liver cells were increased the lipid droplet, change of mitochondria in the GalN compared with LE200. These results suggest that administration of water extract of Lithospermum erythrorhizon suppress or retard galactosamine induced acute liver injury.

The Beneficial Effect of Melatonin for Toluene Hepatotoxicity in Rats

  • Bae, Si-Woo;Yoon, In-Sook
    • Biomedical Science Letters
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    • v.7 no.3
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    • pp.99-102
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    • 2001
  • Toluene is mainly metabolized in liver by oxidative pathway. Oxigen free radicals occur through the process of toluene metabolism Therefore it causes tissue and cell min by the oxygen free radicals from the metabolism of toluene. Melatonin acts as a highly efficient free radical scavenger that protects cells from damage by oxygen free radicals. To test this hypothesis, toluene hepatotoxicity was induced by an abdominal injection of toluene. To see if the melatonin protects the rat's liver, melatonin was administrated orally, at the time of each toluene injection. Aspartate aminotransferase(AST), alanin aminotransferase(ALT), latic dehydrogenase(LDH) and alkaline phosphatase(ALP) levels in serum were measured to estimate hepatic function. Malondialdehyde(MDA), which gives an indirect index of oxidative injury was also measured. Hippuric acid is the last metabolic Production of toluene was measured by HPLC. There were significantly higher in AST, ALT, LDH, MDA and hippuric acid in toluene group, but there were no significant difference in melatonin group except ALT and hippuric acid. There was significantly lower in ALP level in toluene group, but there was no significant difference melatonin group, suggesting a significant hepatotoxicity due to oxygen free radicals through the process of toluene metabolism Melatonin treatment significantly protected hepatic function and free radical-mediated injury in the liver against toluene-induced changes. Accordingly, this study shows that melatonin is helpful in protecting liver injury by acute toluene intoxication.

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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.