• 한국해양바이오학회지
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• 제14권2호
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• pp.61-68
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• 2022

This study aimed to investigate the hepatoprotective activities of the sea cucumber products, including extracts and hydrolysates, in vitro and in vivo. Dried sea cucumber, produced on the western coast of Korea, was boiled in water or 70% ethanol at 85℃ or 100℃ for 18 or 24 h, respectively, to extract bioactive compounds. The enzymatic hydrolysates were prepared by reacting the dried sea cucumber with pepsin or neutral protease (PNL) under optimal enzyme conditions. The anti-inflammatory effect of the samples was investigated using RAW 264.7 cells treated with lipopolysaccharide (LPS). The amount of nitric oxide (NO) was produced from the cells treated with LPS and each sample was compared. Therefore, the pepsin hydrolysate treatment decreased NO production compared to LPS sole treatment. Furthermore, the effects of the samples on cell injury in the hepatic cell line and bisphenolA-induced hepatic injury mouse model were investigated. The water extracts and the pepsin hydrolysates of sea cucumber significantly inhibited cell injury generated in the hepatocytes without cytotoxicity (p < 0.05), whereas the ethanol extracts were cytotoxic. However, these results indicate that the extracts and the enzymatic hydrolysates derived from sea cucumber can be used as beneficial materials for inhibiting liver damage.

• 대한방사선기술학회지:방사선기술과학
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• 제39권4호
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• pp.623-630
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• 2016

방사선 피폭에 의한 간조직의 장해는 경화성 위축으로 복수가 발생하고 황달과 피로감이 수반된다. 이러한 장해에는 간세포의 형태학적 변화가 동반되고 소기관들의 손상이 연관되어 있다. 본 연구는 이러한 소기관들의 형태적 손상을 알아보고자 하였다. 특히 에너지 대사와 관련된 미토콘드리아와 세포질그물 핵막을 중심으로 관찰하였으며, 방사선 방어제 연구와 병행하였다. 방어제는 혈류 증가 작용이 있는 알리인을 투여하였다. 세포 관찰은 투과전자현미경을 활용하였다. 실험결과, 7 Gy 전신 조사에서 간세포의 핵막이 비후되고, 소기관들 주변에 염증성 변화가 관찰되었다. 20일 경과된 세포에서는 과산화소체와 미토콘드리아 막이 손상되었고 세포질에서 공포가 확인되었다. 30일 경과된 세포에서는 거대한 지방세포들이 관찰되었고. 조면소포체에는 리보솜이 분리된 것을 확인하였다. 알리인 투여 후 간세포에서는 핵막 주변에 많은 수의 조면소포체들이 선명하게 관찰되었고 핵막도 비후되지 않았다. 세포질에는 공포화되거나 염증성 증후들이 관찰되지 않았다. 미토콘드리아의 막손상도 없었으며 글리코겐도 정상적으로 확인되었다. 따라서 일부 방어효과가 있는 것으로 확인되었다.

• 대한임상검사과학회지
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• 제36권1호
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• pp.55-63
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• 2004

The hepatotherapeutic effect of the extract of Lycii fructus has been studied in rats against $CCl_4$ induced liver toxicity. The rats were orally treated with $CCl_4$ (corn oil/$CCl_4$ 1:1, $1m{\ell}/kg$) and then $CCl_4$ ($0.5m{\ell}/kg$) administered four times for 2 weeks. The extracts of L. fructus have been administered every day for 2 weeks after the last $CCl_4$ injection. The experimental groups consisted of negative control (G1), positive control ($CCl_4$ alone; G2), extract of L. fructus (50 mg/kg; G3, 100 mg/kg; G4, 200 mg/kg; G5), respectively. There was a significant decrement to G2 on the serum level of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in G5. Also, the content of thiobarbituric acid reactive substance, and phosphatidylcholine hydroperxidase, a marker of lipid peroxidation, in the liver were decreased significantly G5 and G4 compared with G2. Although, catalase or superoxide dismutase, antioxidant enzyme, in the liver were decreased significantly too, it would not be a good sign for the liver. In histopathological findings, such a hepatocellular vacuolar degeneration, lobular restructure, cellular infiltration, necrosis, and so on were shown severely in G2. However, G4 and G5 was shown a mild cytoplasmic vacuolation and inflammatory cell. In conclusion, as a protection against cell damage, lipid peroxidation and serum level, it suggested that the extract of Lycii fructus would have been a therapeutic effect of liver injury directly.

• Toxicological Research
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• 제17권3호
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• pp.187-194
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• 2001

The oxidative stress causes the cell damage and death and thereby, stimulates membrane lipid peroxidation. In this study, the correlation between the lipid peroxidation product and the parameter of liver fibrosis (cirrhosis) was investigated in cholestasis induced rats. The Sprague-Dawley rats were divided into 3 groups (sham: sham operation, BDL/S-I and BDL/S-II : bile duct ligation/scission) and were observed for 2 or 4 weeks. After observation period, the organs were weighed and the ratio of organ weight/body weight was calculated. Sera and liver tissue were used for the measurement of malondealdehyde (MDA), parameter of clinical biochemistry, total collagen content and the staining. The ratio of organ weight/body weight in BDL/S-I and BDL/S-II was significantly increased compared to sham operated group. Serological parameters (Alanine transaminase, Aspartate transaminase, Alkaline phosphatase and Total bilirubin) in BDL/S-I and BDL/S-II group were significantly higher than those in sham operated group. Concentration of MDA in BDL/S-I (261%) and BDL/S-II(790%) was significantly increased compared to MDA in sham operated group. And the content of hydroxyproline (hyp) in BDL/S-I and BDL/S-II group was significantly increased 2~4 times than in sham operated group. The good correlations between hyp in liver tissue and MDA in sera of sham operated group and all operated group were found (r=0.825). The significantly higher value of MDA, hyp and serological parameters in BDL/S-I and BDL/S-II group suggests the stimulation of lipid peroxidation and chronic liver damage. Especially the activation of lipid peroxidation and the stimulation of liver fibrosis was stronger in BDL/S-II group than in BDL/S-I group. The stronger fibrosis, portal-portal septum formation, the more massive bile duct proliferation in portal triads and stroma, and hepatocytes swelling were observed in liver tissue of and BDL/S-II group compared to BDL/S-I group. Conclusively, a good correlation between MDA as a lipid peroxidation marker and hyp as a liver fibrotic parameter could be connected with the process of liver fibrosis. Moreover, cholestasis condition may cause jaundice, activation of lipid peroxidation, and collagen accumulation in liver. Additionally, optimal observation period of bile duct obstruction for the screening of antioxidant and antifibrotic effect in rats would be four weeks.

• The Korean Journal of Physiology and Pharmacology
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• 제4권2호
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• pp.121-127
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• 2000

Intracellular accumulation of bile acids in the hepatocytes during cholestasis is thought to be pathogenic in cholestatic liver diseases. The objective of this study was to determine the role of lipid peroxidation and glutathione on the bile acid-induced hepatic cell death mechanism in primary cultured rat hepatocytes. To induce hepatic cell death, we incubated primary cultured rat hepatocytes with glycochenodeoxycholic acid $(GCDC;\;0{\sim}400\;{\mu}M)$ for 3 hours. In electron microscopic examination and agarose gel electrophoresis, low concentration of GCDC treatment mainly induced apoptotic feature. Whereas $400\;{\mu}M$ GCDC treated cells demonstrated both apoptosis and necrosis. Lipid peroxidation was increased dose-dependently in GCDC treated hepatocyte. And this was also accompanied by decreased glutathione. Therefore, oxygen free radical damage may play a partial role in GCDC-induced hepatic cell death.

• 한국임상수의학회지
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• 제22권3호
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• pp.206-213
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• 2005

This experiment was conducted to find out the therapeutic effect of Artemisia capillaris extracts on hepatic damage in rats induced by carbon tetrachloride ($CCl_{4}$). In this experiment, 96 Sprague-Dawley rats were used as experimental groups, which were divided into 4 groups; control group(A), $CCl_{4}$-treated group(B), $CCl_{4}$+Artemisia extract-treated group(C) and $CCl_{4}$+silymarin-treated group(D). The B, C, D group were administrated single dose of $CCl_{4}$(2.5 ml/kg) to induce acute hepatic injury. C group was administrated with Artemisia capillaris extract(200 mg/kg/day) and D group treated with silymarin(50 mg/kg/day) for 7 days. Hematological, ultrasonographical, histological examinations and examination of antioxidant activity were also performed in all groups. AST and ALT activities of C group were significantly decreased compared with B group. The activities of AST and ALT in C and D groups returned to the normal range more rapidly than those of B group. In ultrasonographic examination, the echogenicity of liver in C group was significantly decreased compared with B group. Also C and D group had tended to recover faster than B group on liver histogram. Histologically, the percentage of degenerative regions and degenerative cell numbers in peri-central vein hepatic parenchyma of C and D group were significantly decreased compared with B group. In examination of lipid peroxidation, malondialdehyde of hepatic tissue in C group was decreased as compared with B group. In examination of antioxidant enzyme activity in liver, glutathione peroxidase and catalase activities were significantly increased compared with B group. As results of this study, it is thought that A. capillaris extract has therapeutic effects on hepatic injury induced by carbon tetrachloride, and has the similar therapeutic effects as silymarin in rats.

• 생명과학회지
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• 제34권4호
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• pp.227-235
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• 2024

약물이나 허브 제품으로 인한 간세포 손상은 이러한 화합물을 만성적으로 투여할 때 일어날 수 있는 중요한 문제 중 하나이다. 따라서 여러 가지의 치료 과정 중 간세포 생존율을 향상시키는 것은, 약물 적용에 있어 광범위한 기회를 제공할 수 있다. Valproic acid (VPA)는 자연적으로 발생하는 발레르산에서 파생된 분지형 단사슬 지방산으로 뇌전증과 발작을 치료하는 데 일반적으로 사용된다. 뿐만 아니라 VPA는 암, HIV 치료, 신경 퇴행성 질환에 수많은 효과를 발휘하지만, 간에 대한 VPA의 잠재적인 영향과 그 작용 메커니즘은 완전히 설명되지 않았다. 여기서, 우리는 VPA의 처리가 쥐 간세포(Hepa1c1c7)에서 PPAR 알파(PPAR-α)와 섬유아세포 성장 인자 21(FGF21)의 전사 수준을 증가시킨다는 것을 입증했다. VPA에 의해 유도된 FGF21 발현은 PPAR-α 결손 조건에서 상당히 억제되었다. 후속 실험에서 FGF21 신호 경로가 FGF 수용체 억제제에 의해 차단되었을 때, 간세포 생존력이 크게 억제되었음을 보여주었다. 마지막으로, 우리는 AMPK 인산화가 VPA에 의해 유도된 PPAR-α 증가에 작용하지 않는다는 것을 추가로 확인했다. 이러한 결과는 FGF21 발현의 증가가 VPA에 의해 유도된 간 독성을 완화시킬 수 있다는 것을 제시하며, 이와 같은 결과는 FGF21의 증감 여부가 VPA 치료 중 나타날 수 있는 간 손상을 예측하는 잠재적인 바이오마커로 사용될 수 있음을 제시한다.

• 대한의생명과학회지
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• 제7권3호
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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.

• Journal of Nutrition and Health
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• 제21권3호
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• pp.154-163
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• 1988

Effects of alchohol and fat content in a balanced diet on chemical composition and morphology of liver were investigated in growing rats. Fourth eight male rats of Sprague-Dawley strain weighing about 160g were divided into 4 groups ; high fat diet group, alcohol-administered high fat diet group, low fat diet group and alcohol-administered high fat diet group, low fat diet group and alcohol-administered low fat diet group. High and low fat diets supplied 30% and 12%, respectively, of total calorie intake from fat, and alcohol was given by adding ethanol in drinking waster at 10%. Diets contained adequate amounts of all nutrients required for rats, including lipotrpoic agents(choline and methionine) to minimize effects of factors other than alcohol on liver damage. Ratios of liver weight to body weight were statistically different among groups. Liver/dody weight ratios alcohol-administered rats were significantly higher than those of non-alcohol groups after 6 weeks treatment. Although total lipid and triglyceride per gram liver were increased in alcohol-administered rats, especially low fat diet fed rats, the values were not significantly different. Opticmicroscopical observation revealed increase in cell size and no change in morphology of liver. Examination of hepatocytes by electron microscopy showed that fat droplets were observed in all groups but enlarged in the alcohol-administered low fat diet fed rat. Contents of protein, cholesterol and phospholipid were not affected by alcohol consumption. The level of lipid peroxide was significantly lower in the livers of alcohol-administered rats than in the livers of non-alcohol groups. The results of this study indicate that even moderate alcohol drinking and dietary fat content did not affect any significant change in composition and morphology of liver until 6 week treatment but that even moderate alcohol drinking caused some signs of steatosis of liver.

• 동아시아식생활학회지
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• 제16권4호
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• pp.414-420
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• 2006

The present study evaluated the effects of pomegranate peel (Granati pericarpium) extract on the lipid profiles and antioxidant biomarkers in mice fed a high fat and cholesterol diet: the measured biomarkers included the TBARS value, GPx, GR, SOD and GST activities. Body fat depositions were significantly decreased in the group that received pomegranate peel. In addition, the activities of GPx, GST and SOD were significantly higher in the liver and plasma of the pomegranate peel group than in the control group. Also, the pomegranate peel diet decreased lipid peroxidation of the liver and kidney. Alkaline single-cell gel electrophoresis (comet assay) showed that the DNA damage in the plasma of the pomegranate peel group was decreased compared to that of control. The present results show that a diet with added pomegranate peel exerts protective effects against oxidative DNA damage and lipid peroxidation possibly via effects on the free radical levels in mice fed a high fat and cholesterol diet.