• Title/Summary/Keyword: Human liver

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Lactobacillus Aggravate Bile Duct Ligation-Induced Liver Inflammation and Fibrosis in Mice

  • Roh, Yoon Seok;Cho, Ara;Cha, Youn-Soo;Oh, Suk-Heung;Lim, Chae Woong;Kim, Bumseok
    • Toxicological Research
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    • v.34 no.3
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    • pp.241-247
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    • 2018
  • Lactobacillus (LAB) have been reported to exert both harmful and beneficial effects on human and animal health. Recently, it has been reported that dysbiosis and bacterial translocation contribute to liver fibrosis. However, the role of Gram-positive LAB in the situation of chronic liver diseases has not been yet elucidated. Liver injury was induced by bile duct ligation (BDL) in LAB or control-administered mice. Liver fibrosis was enhanced in LAB-administered mice compared with control-treated mice as demonstrated by quantification of Sirius-red positive area, hydroxyproline contents and fibrosis-related genes ($Col1{\alpha}1$, Acta2, Timp1, Tgfb1). Moreover, LAB-administered mice were more susceptible to BDL-induced liver injury as shown by increased ALT and AST level of LAB group compared with control group at 5 days post BDL. Consistent with serum level, inflammatory cytokines ($TNF-{\alpha}$, IL-6 and $IL-1{\beta}$) were also significantly increased in LAB-treated mice. Of note, LAB-treated liver showed increased lipoteichoic acid (LTA) expression compared with control-treated liver, indicating that LAB-derived LTA may translocate from intestine to liver via portal vein. Indeed, responsible receptor or inflammatory factor (PAFR and iNOS) for LTA were upregulated in LAB-administered group. The present findings demonstrate that administration of LAB increases LTA translocation to liver and induces profibrogenic inflammatory milieu, leading to aggravation of liver fibrosis. The current study provides new cautious information of LAB for liver fibrosis patients to prevent the detrimental effect of LAB supplements.

Method for Evaluating Metabolic Functions of Drugs in Bioartificial Liver

  • Park, Yueng-Guen;Hiroo Iwata;Seiji Satoh;Takehiko Uesugi;Ryu, Hwa-Won
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.8 no.5
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    • pp.279-285
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    • 2003
  • Lidocaine and galactose loading tests were performed on a bioartificial liver (BAL), an extracorporeal medical device incorporating living hepatocytes in a cartridge without a transport barrier across the membranes. The concentration changes were analyzed using pharmacokinetic equations to evaluate the efficacy and limitation of the proposed method. Lidocaine and galactose were found to be suitable drugs for a quantitative evaluation of the BAL functions, as they did not interact with the plasma proteins or blood vessels, making their concentrations easy to determine. The drug concentration changes after drug loading were easily analyzed using pharmacokinetic equations, and the BAL functions quantitatively expressed by pharmacokinetic parameters, such as the clearance (CL) and galactose elimination capacity (GEC). In addition, these two drugs have already been used in clinical tests to evaluate human liver functions over long periods, and lidocaine CL values and GEC values reported for a normal human liver. Thus, a comparison of the CL and GEC values for the BAL and a natural liver revealed what proportion of normal liver functions could be replaced by the BAL.

Investigating herbal active ingredients and systems-level mechanisms on the human cancers (암치료를 위한 네트워크 기반 접근방식 활용 시스템 수준 연구)

  • Lee, Won-Yung
    • Herbal Formula Science
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    • v.30 no.3
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    • pp.175-182
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    • 2022
  • Objective : This study aims to investigate the active ingredients and potential mechanisms of the beneficial herb on human cancers such as the liver by employing network pharmacology. Methods : Ingredients and their target information was obtained from various databases such as TM-MC, TTD, and Drugbank. Related protein for liver cancer was retrieved from the Comparative Toxicogenomics Database and literature. A hypergeometric test and gene set enrichment analysis were conducted to evaluate associations between protein targets of red ginseng (Panax ginseng C. A. Meyer) and liver cancer-related proteins and identify related signaling pathways, respectively. Network proximity was employed to identify active ingredients of red ginseng on liver cancer. Results : A compound-target network of red ginseng was constructed, which consisted of 363 edges between 53 ingredients and 121 protein targets. MAPK signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, TGF-beta signaling pathway, and cell cycle pathway was significantly associated with protein targets of red ginseng. Network proximity results indicated that Ginsenoside Rg1, Acetic Acid, Ginsenoside Rh2, 20(R)-Ginsenoside Rg3, Notoginsenoside R1, Ginsenoside Rk1, 2-Methylfuran, Hexanal, Ginsenoside Rd, Ginsenoside Rh1 could be active ingredients of red ginseng against liver cancer. Conclusion : This study suggests that network-based approaches could be useful to explore potential mechanisms and active ingredients of red ginseng for liver cancer.

GIS-Based Spatial Statistical Analysis of Risk Areas for Liver Flukes in Surin Province of Thailand

  • Rujirakul, Ratana;Ueng-arporn, Naporn;Kaewpitoon, Soraya;Loyd, Ryan J;Kaewthani, Sarochinee;Kaewpitoon, Natthawut
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2323-2326
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    • 2015
  • It is urgently necessary to be aware of the distribution and risk areas of liver fluke, Opisthorchis viverrini, for proper allocation of prevention and control measures. This study aimed to investigate the human behavior, and environmental factors influencing the distribution in Surin Province of Thailand, and to build a model using stepwise multiple regression analysis with a geographic information system (GIS) on environment and climate data. The relationship between the human behavior, attitudes (<50%; $X_{111}$), environmental factors like population density ($148-169pop/km^2$; $X_{73}$), and land use as wetland ($X_{64}$), were correlated with the liver fluke disease distribution at 0.000, 0.034, and 0.006 levels, respectively. Multiple regression analysis, by equations OV= -0.599 + 0.005(population density ($148-169pop/km^2$); $X_{73}$) + 0.040 (human attitude (<50%); $X_{111}$) +0.022 (land used (wetland; X64), was used to predict the distribution of liver fluke. OV is the patients of liver fluke infection, R Square= 0.878, and, Adjust R Square= 0.849. By GIS analysis, we found Si Narong, Sangkha, Phanom Dong Rak, Mueang Surin, Non Narai, Samrong Thap, Chumphon Buri, and Rattanaburi to have the highest distributions in Surin province. In conclusion, the combination of GIS and statistical analysis can help simulate the spatial distribution and risk areas of liver fluke, and thus may be an important tool for future planning of prevention and control measures.

In vitro metabolism of a new protective agent, KR-31543 in human liver microsomes

  • Ji, Hye-Young;Kim, Sook-Jin;Lee, Hong-Il;Lee, Seung-Seok;Lee, Dong-Ha;Lim, Hong;Lee, Hye-Suk
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.286.2-287
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    • 2003
  • The purpose of this paper was to identify the metabolic pathway of a new neuroprotective agent, KR-31543 for ischemia-reperfusion damage in human liver microsomes and characterize cytochrome P450 (CYP) enzymes involved in the in vitro metabolism of KR-31543 generates two metabolites in human liver microsomes : M1, N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine and M2, hydroxy-KR-31543. (omitted)

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Estimation of Ultrasound Attenuation Coefficients with Nonlinear Frequency Dependency for Human Liver (인체간 조직의 비선형 초음파 감쇄상수 추정)

  • Lee, No-Sung;Woo, Kwang-Bang;Yu, Hyung-Shik
    • Journal of Biomedical Engineering Research
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    • v.11 no.1
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    • pp.121-130
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    • 1990
  • In this study, the coefficients of ultrasound attenuation for human liver were determined in 6 normal humans and in 38 patients with diffuse liver disease. The coefficients with linear frequency dependency as well as nonlinear frequency dependency were evaluated. Gaussian pulse propagating in a lossy medium suffers downshifting of a center frequency and decreasing in the bandwidth. Such changes in frequency domain spectrum were quantified in terms of changes in the attenuation coefficients with nonlinear dependency, which in turn improve clinical Implications of the coefficients. Statistical analysis shows that the attenuation coefficients evaluated with nonlinear dependency reflect an improved accuracy for the diffuse liver disease than those with linear dependency. The discriminant analysis also indicate the improved classification with nonlinear dependency(75%) than with linear dependency(61%).

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Regulation of the Hepatic Antioxidative System by Astaxanthin in the Rats

  • Kang, Ji-One;Kim, Sung-Jin;Kim, Harriet
    • Preventive Nutrition and Food Science
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    • v.4 no.4
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    • pp.251-254
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    • 1999
  • Astaxanthin is one of many carotenoids present in marine animals, vegetables and fruits. Since carotenoids are known to exert antioxidant actions, we explored to determine if astaxnathin could have such regulatory actions in normal-and $CCl_4$-treated rat liver. Astaxanthin treatment caused a slight increase in $\alpha$-tocopherol levels in the control rat liver. Glucose-6-phosphatase activity was significantly increased by astaxanthin in a dose-dependent manner and its activity decreased in response to $CCl_4$treatment was slightly inhibited by astaxanthin. These results suggest that astaxanthin could protect liver damages induced by $CCl_4$via inhibiting lipid peroxidation and it may have a potential to activate the anti-oxidant system of normal liver by stimulating $\alpha$-tocopherol production.

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Evaluation of Metabolic Stability of Kinsenoside, an Antidiabetic Candidate, in Rat and Human Liver Microsomes

  • Rehman, Shaheed Ur;Kim, n Sook;Choi, Min Sun;Luo, Zengwei;Yao, Guangming;Xue, Yongbo;Zhang, Yonghui;Yoo, Hye Hyun
    • Mass Spectrometry Letters
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    • v.6 no.2
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    • pp.48-51
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    • 2015
  • Kinsenoside is a principle bioactive compound of Anoectochilus formosanus. It exhibits various pharmacological effects such as antihyperglycemic, antioxidant, anti-inflammatory, immunostimulating, and hepatoprotective activities and has recently been developed as an antidiabetic drug candidate. In this study, as part of an in vitro pharmacokinetic study, the stability of kinsenoside in rat and human liver microsomes was evaluated. Kinsenoside was found to have good metabolic stability in both rat and human liver microsomes. These results will provide useful information for further in vivo pharmacokinetic and metabolism studies.

Human Placenta Extract Could Promote Proliferating Cell Nuclear Antigen Expression during Liver Regeneration Induced by Partial Hepatectomy in Rats

  • Kim, Ji-Hyun;Han, Kyu-Boem;Choi, Yong-Soo;Lee, Young-Jun;Yoon, Kwang-Ho;Han, Man-Deuk;Kim, Wan-Jong
    • Applied Microscopy
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    • v.42 no.3
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    • pp.115-123
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    • 2012
  • Human placenta extract (hPE) has therapeutic potential against certain diseases such as burn injury, liver cirrhosis and chronic wound through stimulating tissue repair processes. However, the effects of hPE on liver regeneration in animals are unknown. This study investigated the effect of hPE on the expression of proliferating cell nuclear antigen (PCNA) during liver regeneration induced by partial hepatectomy (PH) in rats. The activities of AST, ALT and ALP increased during a few days after PH. A high level of ALP was particularly seen at day 3 in the control group. All the levels of experimental groups were normalized by day 5 after PH. On immunohistochemistry, the expression of PCNA increased at the early days, showed a peak at day 3 after PH. The PCNA staining was more obvious in the experimental group over the whole period. By western blotting, PCNA seemed to be more strongly expressed in the hPE injected group in the early stage and fell to almost undetectable levels at day 7. On immunocytochemical observations, the number of PCNA-gold particles in the nuclei at day 1 of the hPE treated groups was more than those of the untreated groups. The results suggest that hPE could accelerate liver regeneration induced by PH involving the expression of PCNA in rats.

Effect of Dietary Fat and Genistein on Lipid Metabolism and Antioxidant Activity in Hyperlipidemic Male Rats induced High Fat Diet (고지방식이로 유도된 고지혈증 모델 흰쥐에서 지방과 제니스테인 섭취가 지질대사 및 항산화능에 미치는 영향)

  • Kim Mi-Hyun;Jang So-Young;Lee Yeon-Sook
    • Journal of Nutrition and Health
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    • v.39 no.2
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    • pp.100-108
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    • 2006
  • This study was conducted to investigate whether dietary factors, normal fat and genistein leads to beneficial improvement of lipid metabolism and oxidative stress in adult hyperlipidemic male rats. Seven wk-old male SD rats were fed high fat diet (15% fat, 1% cholesterol) for 4 wks for induction of hyperlipidemic model rat. Weight-matched rats were then assigned to four groups according to dietary fat level (7% or 15% fat) and genistein contents (0 or 320 mg/kg diet). Food intake was significantly decreased by both high fat intake and genistein supplementation compared with normal fat intake and genistein no supplementaion. But weight gain was significantly decreased by genistein supplementation in normal fat intake compared with the other groups. Total lipid, total cholesterol and triglyceride in serum and liver were significantly decreased by normal fat intake compared with high fat intake. But total cholesterol in liver was significantly increased by genistein supplementation in both high fat and normal fat intake. TBARS in serum and liver was less produced by normal fat intake compared with high fat intake but TBARS in liver was significantly increased by genistein supplementation compared with genistein no supplementation in normal fat intake. Glutathione reductase activity in erythrocytes was significantly reduced by genistein supplementation in normal fat intake compared with the other groups. Glutathione peroxidase and glutathione reductase activities in liver were significantly inhibited by normal fat intake compared with high fat intake. Catalase activity in liver was significantly increased by genistein supplementation compared with genistein no supplementation in high fat intake. Nitrite was significantly decreased by normal fat intake compared with high fat intake. These results suggest that normal fat intake has the treatment effect against risk factors related with cardiovascular disease by reducing lipid profiles, lipid peroxidation. And genistein shows action as a antioxidant replacing antioxidant enzymes but also may act as prooxidant causing the production of TBARS.