• Title/Summary/Keyword: Hepatic damage

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The Role of Lipid Peroxidation and Glutathione on the Glycochenodeoxycholic Acid-Induced Cell Death in Primary Cultured Rat Hepatocytes

  • Chu, Sang-Hui;Park, Wol-Mi;Lee, Kyung-Eun;Pae, Young-Sook
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.2
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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.

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Effects of Larval Extracts from P. brevitarsis seulensison Cytokine and Diagnostic Marker in Carbon Tetrachloride-Administered SD Rats

  • Lee, Ji-Sook;Kwon, Ohseok;Hwang, Seock-Yeon;Yun, Chi-Young
    • Korean Journal of Clinical Laboratory Science
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    • v.43 no.3
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    • pp.113-119
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    • 2011
  • This study was designed to determine the effects of larval extracts from Protaetia brevitarsis seulensis shade dried larva from Korea and China on liver tissues of hepatic injury groups. The experimental groups are divided into five groups; Normal, carbon tetrachloride single injection ($CCl_4$), Pb-CHI ($CCl_4$ + P. brevitarsis shade dried larva from China), Pb-KOR ($CCl_4$ + P. brevitarsis shade dried larva from Korea) and SIL ($CCl_4$ + 0.35% silymarin) groups. Sprague Dawley rats were oral injected with $CCl_4$ at a dose l mg/kg (20% in corn oil) for induction of liver damage for 4 weeks. Each experimental group was fed with a dose 50 mg/kg of larval extracts based on medicinal preparations from 3 weeks to 4 weeks after $CCl_4$ treatment. At the end of 4 weeks, we evaluated the serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transferase (GPT), alkaline phosphatase (ALP) and blood urea nitrogen (BUN) in serum and the cytokine levels of tumor necrosis factor-${\alpha}$) (TNF-${\alpha}$) and transforming growth factor-${\beta}$ (TGF-${\beta}$) in the cells isolated from spleen and liver. The histological analysis was also conducted. The $CCl_4$ injection reduced body weight, induced congestion of middle lobe and hepatocytic degeneration, resulting in disintegration of hepatic cords, and increased biochemical markers of blood related to hepatic injury. On the other hand, the Pb-CHI and Pb-KOR group decreased the levels of biochemical markers in blood and cytokine levels in spleen and liver. Especially, the Pb-KOR group facilitated the recovery of biochemical values of blood related to hepatic injury, hepatic lesions and fibrosis. Taken together, larval extract from P. brevitarsis might prevent acute hepatotoxicity and enhance the recovery of liver fibrosis and cirrhosis induced by $CCl_4$, and the ingredients could be a promising candidate for the prevention and treatment of hepatic disorders.

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Effects of Onion Juice on Ethanol-Induced Hepatic Lipid Persoxidation in Rats (양파즙이 에탄올에 의한 백서의 지질산화물 생성에 미치는 영향)

  • 박평심;이병래;이명렬
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.23 no.5
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    • pp.750-756
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    • 1994
  • The effect of onion juice on ethanol -induced lipid peroxidation were studied were studied in rats. The contents of thiobarbituric acid (TBA) -reactants increased significantly in liver thanol(4ml/kg/day) administered -rats. The activities of serum alanine aminotransferase and alkaline phosphatase increased by ethanol administration compared with control group, but alterations of antioxidant enzymes activities in liver of ethanol administered rats were not significant vs control group. The glutathione contents in liver decreased by ethanol , whereas the glutathione level increased in ethanol and onion juice group compared with ethanol group. The contents of hepatic TBA-reactants and serum aminotrasnferase activity in ethanol group were reduced by onion juice administration. In these results, increased hepatic TBA-reactants of liver in ethanol group might be due to decreased glutathione contents in liver. Reduced glutathione (GSH) plays an important roles in the liver in several detoxification and the reduction of lipid peroxides. So the protective effects of onion juice on ethanol-induced increment of TBA-reactants may be due to the increament of lgutathions content. The glutathione depletion by ethanol was an important factor of ethanol-induced cell damage, and the prevention of onion juice to the glutathione depletion reduced by ethanol may be an important factor on the protection from ethanol-induced lipid perpxidation in rats.

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Protective effects of Korean red ginseng extract on cadmium-induced hepatic toxicity in rats

  • Park, Sook Jahr;Lee, Jong Rok;Jo, Mi Jeong;Park, Sang Mi;Ku, Sae Kwang;Kim, Sang Chan
    • Journal of Ginseng Research
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    • v.37 no.1
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    • pp.37-44
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    • 2013
  • Korean red ginseng is known to regulate the immune system and help the body struggle infection and disease. Cadmium is widely distributed in the environment due to its use in industry. Exposure to cadmium is problematic causing organ dysfunction. This study was conducted to evaluate the protective effect of Korean red ginseng extract (RGE) against cadmium-induced hepatotoxicity in rats. In experiments, animals were orally administrated with RGE (25, 50 mg/kg) for 7 d and then intravenously injected with cadmium ($CdCl_2$, 4 mg/kg) to induce acute hepatotoxicity. Cadmium caused the elevated levels of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase in serum. In contrast, pretreatment with RGE significantly reduced those serum indexes related with liver damage. In histopathological analysis, RGE decreased the centrilobular necrosis around central veins and the peripheral hemorrhage around portal triads. Moreover, RGE restored the deficit in hepatic glutathione level resulting from cadmium treatment. RGE also inhibited the increase in the expression of Bad, a representative apoptosis marker protein, induced by cadmium treatment. Collectively, these results demonstrate that RGE can reduce the cadmium-induced hepatic toxicity, partly via anti-oxidative and anti-apoptotic process.

Dose-dependent Antifibrotic Effect of Polysaccharide from Mycelium of Ganoderma Lucidum on Liver Biliary Cirrhosis in Rats (담도결찰 흰쥐에서 영지배양 균사체 유래 다당체의 항섬유화 효과 검색 및 용량의존성시험)

  • Park, Eun-Jeon;Ko, Geon-Il;Kim, Jae-Baek;Sohn, Dong-Hwan
    • YAKHAK HOEJI
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    • v.41 no.2
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    • pp.220-224
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    • 1997
  • This study was carried out to investigate the dose dependent antifibrotic effects of polysaccharide from mycelium of Ganoderma lucidum. The experimental hepatic cirrhosis was induced by bile duct ligation/scission (BDL/S) in rats. BDL/S rats in each group were dosed 0.5 mg, 2.0 mg, 5.0 mg or 10.O mg/rat/day orally for 4 weeks after the operation. Antifibrotic effects were evaluated by serum biochemical values, hydroxyproline contents, and light microscopical histology. The results obtained were as follows: 1) Hydroxyproline contents in liver of 5.0 and 10.0mg polysaccharide-treated BDL/S rats were significantly reduced 2) In serum test, ALT, AST, ALP values in polysaccharide from Ganoderma lucidum-treated group were lower than BDL/S control group 3) The hepatic damage such as hepatocellular necrosis, inflammation, bile duct proliferation and fibrosis was less severe in the livers of 2.0 mg and 5.0 mg polysaccharide-treated rats. These results suggest that polysaccharide from mycelium of Ganoderma lucidum to be a promising agent for the inhibition of hepatic cirrhosis.

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Protective Effects of $\alpha$-Tocopherol and Ischemic Preconditioning on Hepatic Reperfusion Injury

  • Lee Woo-Yang;Lee Sun-Mee
    • Archives of Pharmacal Research
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    • v.28 no.12
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    • pp.1392-1399
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    • 2005
  • This study evaluated the effect of $\alpha$-tocopherol ($\alpha$-TC), ischemic preconditioning (IPC) or a combination on the extent of mitochondrial injury caused by hepatic ischemia/reperfusion (I/R). Rats were pretreated with $\alpha$-TC (20 mg/kg per day, i.p.) for 3 days before sustained ischemia. A rat liver was preconditioned with 10 min of ischemia and 10 min of reperfusion, and was then subjected to 90 min of ischemia followed by 5 h or 24 h of reperfusion. I/R increased the aminotransferase activity and mitochondrial lipid peroxidation, whereas it decreased the mitochondrial glutamate dehydrogenase activity. $\alpha$-TC and IPC individually attenuated these changes. $\alpha$-TC combined with IPC ($\alpha$-TC+IPC) did not further attenuate the changes. The mitochondrial glutathione content decreased after 5 h reperfusion. This decrease was attenuated by $\alpha$-TC, IPC, and $\alpha$-TC+IPC. The significant production of peroxides observed after 10 min reperfusion subsequent to sustained ischemia was attenuated by $\alpha$-TC, IPC, and $\alpha$-TC+IPC. The mitochondria isolated after I/R were rapidly swollen. However, this swelling rate was reduced by $\alpha$­TC, IPC, and $\alpha$-TC+IPC. These results suggest that either $\alpha$-TC or IPC reduces the level of mitochondrial damage associated with oxidative stress caused by hepatic I/R, but $\alpha$- TC combined with IPC offers no significant additional protection.

Glycine alleviated diquat-induced hepatic injury via inhibiting ferroptosis in weaned piglets

  • Hua, Hongwei;Xu, Xiao;Tian, Wei;Li, Pei;Zhu, Huiling;Wang, Wenjun;Liu, Yulan;Xiao, Kan
    • Animal Bioscience
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    • v.35 no.6
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    • pp.938-947
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    • 2022
  • Objective: The beneficial effects of glycine were tested in piglets with diquat-induced hepatic injury. Methods: Thirty-two piglets were assigned by a 2×2 factorial experimental design including glycine supplementation and diquat challenge. After 3 weeks of feeding with a basic diet or a 1% glycine supplemented diet, piglets were challenged with diquat or saline. After 1 week later, the piglets were slaughtered and samples were collected. Results: Our results indicated that glycine alleviated diquat induced morphological hepatic injury, decreased the activities of plasma alanine aminotransferase, aspartate aminotransferase and glutamyl transpeptidase in the piglets under diquat challenge, and increased total antioxidant capacity and antioxidative enzyme activity significantly. Adding glycine enhanced the concentrations of hepatic adenosine triphosphate and adenosine diphosphate. Transmission electron microscope observation showed that diquat induced clear hepatocytes ferroptosis and its effect could be alleviated by glycine to a certain degree. Moreover, glycine significantly affected mRNA and protein expression of ferroptosis-related signals in the liver. Conclusion: These results demonstrated that glycine attenuated liver damage via inhibiting ferroptosis.

Effect of Seeds Extract of Paeonia Lactiflora on Antioxidative System and Lipid Peroxidation of Liver in Rats Fed High-Cholesterol Diet (작약(Paeonia Lactiflora Pall.)씨 추출물이 고콜레스테롤 식이 흰쥐 간조직의 항상화계와 지질과산화에 미치는 영향)

  • 이정민;최상원;조성희;이순재
    • Journal of Nutrition and Health
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    • v.36 no.8
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    • pp.793-800
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    • 2003
  • This study was conducted to investigate the antioxidative effects of Paeonia lactiflora (PL) seeds on antioxidative defense system and lipid peroxidation of liver in rats fed high-cholesterol diet. Sprague-Dawley male rats weighing 100 $\pm$10g were randomly assigned into five experimental groups fed 0.5% cholesterol ; HC group which was not supplemented PL seeds extract, 0.1% methanol extract diet group (MP1 group), 0.2% methanol extract diet group (MP2 group), 0.05% ether-souble fraction diet group (EP1 group) and 0.1 % ether-souble fraction diet group (EP2 group). Experimental diets were fed ad libitum to the rats for 3 weeks. The activity of hepatic superoxide dismutase (SOD) was not significantly different among all the high cholesterol diet groups. The hepatic glutathione peroxidase (GSHpx) activity in MP2 group was increased to 27% compared to HC group. The activity of hepatic catalase (CAT) was not significantly different among the all high cholesterol diet groups. The hepatic glutathione S-transferase (GST) activity in the EP1 and EP2 groups were increased to 12% and 13%, respectively, as compared to HC group. The levels of hepatic TBARS in the MP1, MP2, EP1 and EP2 groups were reduced by 18%, 21%, 20% and 23%, respectively, as compared with HC group. The contents of lipofuscin in liver was not significantly different among all the experimental groups. The results indicated that PL seeds extract may be reduced oxidative damage by activating antioxidative defense system of hepatic in rats fed high-cholesterol diets. (Korean J Nutrition 36(8): 793∼800, 2003)

Ca2+-ATPase and cAMP-mediated Anti-Apoptotic Effects of Acanthopanax senticosus Extracts on Ischemia/Reperfusion Liver Damages

  • Xie, Guang-Hua;Jeong, Jae-Hun;Choi, Sun Eun;Jeong, Seung Il;Park, Kwang-Hyun
    • Korean Journal of Plant Resources
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    • v.30 no.6
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    • pp.647-653
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    • 2017
  • Hepatic ischemia-reperfusion injury (HIRI) is linked with high mortality rate. Several agents have been developed so far to reduce the risk of HIRI. In this study, we investigated the effects of Acanthopanax senticosus extract (AS) on hepatic ischemia-reperfusion. To explore the protective effects of A. senticosus extract injection (ASI) on hepatic ischemia-reperfusion injury rats animal model were used. After the development of HIRI by using clamping method rats were then randomly divided into five groups. Different doses of AS were administered in HIRI rat model. The level of ALT, AST, and MDA content in serum were detected in sham and HIRI groups. The activity of SOD, MPO and $Ca^{2+}-ATPase$, content of MDA, and cAMP in hepatic tissue were also measured. Expression of Bcl-2 and Bax protein were detected by immunohistochemical staining method. Compared with sham group, ASI has the protective effect on the HIRI model in rats. Blood levels of ALT, AST, SOD, MPO, and MDA were significantly lower in ASI group compared with HIRI. Indeed SOD and $Ca^{2+}-ATPase$ activities, MDA content, and cAMP level were improved in ASI group. Furthermore, Bcl-2 and Bax protein were improved in ASI group compared with only HIRI group. These results suggest that AS may provide potential ameliorative therapy by inhibiting the damage signaling mechanism in hepatic ischemia/reperfusion injury model.

Effects of Dietary Peroxidizability Index Values on Hepatic TBARS and Antioxidant Enzyme Activity in 7,12-dimethylbenz[$\alpha$]anthracene-treated Rats

  • Kang Min Jeong;Shin Myoung Suk;Park Tung Nan;Lee Sang Sun
    • Nutritional Sciences
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    • v.9 no.1
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    • pp.14-19
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    • 2006
  • Breast cancer may be the consequence of free radical damage, which is partially caused by the excessive intake of dietary fat and imbalances in antioxidant scavenger system;. In this experiment, we examined! the effects of dietary peroxidizability index (PI) values on hepatic thiobmbituric acid reaction substances (TBARS) and antioxidant enzyme activities in rats treated with 7,12-dimethylbenz[$\alpha$]anthracene (DMBA). Female Sprague-Dawley rats were used and 7,12-DMBA (20 mg/kg body weight) was gastrically intubated at seven weeks of age in order to induce mammary tumors (MT). The levels of dietary PI were 36, 81, 126 and 217 (LPI, MLPI, MHPI and HPI), while dietary polyunsaturated/saturated fatty acids ratio was maintained at the same level (1.0). Fat used in the experiment was mixed with soybean oil, com oil, palm oil, perilla oil, sesame oil, fish oil, and beef tallow. Experimental diets were given for the following 20 weeks. We measured tumor numbers and weights, and then assayed the hepatic TBARS levels and antioxidant enzyme activities such as superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione-S-transferase (GST) and glutathione reductase (GR). The incidence of Mr was the lowest in the MHPI group. The hepatic TBARS level was significantly raised with increasing dietary PI value. The hepatic SOD and GR activities were differed significantly by dietary PI value. The hepatic SOD activity was negatively correlated with dietary PI value and GR activity was the highest in the rats fed the MHPI diet. When the dietary P/S ratio is kept at 1.0, adequate dietary PI value (PI value of 126) may reduce the incidence and growth of Mr, but this benefit may be lost with higher dietary PI value. These results suggest that the awareness of dietary PI values may help to decrease breast cancer incidence and growth.