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  • 1
    Online Resource
    Online Resource
    Chronic Indomethacin Treatment Enhances the Portal-systemic Collateral Vascular Response to Vasopressin in Bile-duct Ligated Rats
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Journal of the Chinese Medical Association Vol. 70, No. 12 ( 2007-12), p. 521-526
    Details
    In: Journal of the Chinese Medical Association, Ovid Technologies (Wolters Kluwer Health), Vol. 70, No. 12 ( 2007-12), p. 521-526
    Type of Medium: Online Resource
    ISSN: 1726-4901
    URL: Article
    DOI: 10.1016/S1726-4901(08)70054-6
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 2202774-9
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  • 2
    Online Resource
    Online Resource
    Vasopressin response and shunting modulation in cirrhotic rats by chronic nitric oxide inhibition
    Wiley ; 2008
    In:  Journal of Gastroenterology and Hepatology Vol. 23, No. 7pt2 ( 2008-07), p. e265-e269
    Details
    In: Journal of Gastroenterology and Hepatology, Wiley, Vol. 23, No. 7pt2 ( 2008-07), p. e265-e269
    Type of Medium: Online Resource
    ISSN: 0815-9319 , 1440-1746
    URL: Issue
    URL: Article
    DOI: 10.1111/jgh.2008.23.issue-7pt2
    DOI: 10.1111/j.1440-1746.2007.05122.x
    Language: English
    Publisher: Wiley
    Publication Date: 2008
    detail.hit.zdb_id: 2006782-3
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  • 3
    Online Resource
    Online Resource
    Glucobrassicin Metabolites Ameliorate the Development of Portal Hypertension and Cirrhosis in Bile Duct-Ligated Rats
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 20, No. 17 ( 2019-08-26), p. 4161-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 20, No. 17 ( 2019-08-26), p. 4161-
    Abstract: Patients suffering from liver cirrhosis are often complicated with the formation of portosystemic collateral vessels, which is associated with the progression of a splanchnic hyperdynamic circulatory state. Alleviating pathological angiogenesis has thus been proposed to be a feasible treatment strategy. Indole-3-carbinol (C9H9NO, I3C) and 3,3′-diindolymethane (DIM), formed by the breakdown of glucosinolate glucobrassicin, are prevalent in cruciferous vegetables and have anti-angiogenesis properties. We aimed to evaluate their influences on portal hypertension, the severity of mesenteric angiogenesis, and portosystemic collaterals in cirrhosis. Sprague-Dawley rats with common bile duct ligation (CBDL)-induced liver cirrhosis or sham operation (surgical control) were randomly allocated to receive I3C (20 mg/kg/3 day), DIM (5 mg/kg/day) or vehicle for 28 days. The systemic and portal hemodynamics, severity of portosystemic shunting, mesenteric angiogenesis, and mesenteric proangiogenic factors protein expressions were evaluated. Compared to vehicle, both DIM and I3C significantly reduced portal pressure, ameliorated liver fibrosis, and down-regulated mesenteric protein expressions of vascular endothelial growth factor and phosphorylated Akt. DIM significantly down-regulated pErk, and I3C down-regulated NFκB, pIκBα protein expressions, and reduced portosystemic shunting degree. The cruciferous vegetable byproducts I3C and DIM not only exerted a portal hypotensive effect but also ameliorated abnormal angiogenesis and portosystemic collaterals in cirrhotic rats.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms20174161
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Chronic cyclooxygenase blockade enhances the vasopressin responsiveness in collaterals of portal hypertensive rats
    Informa UK Limited ; 2006
    In:  Scandinavian Journal of Gastroenterology Vol. 41, No. 12 ( 2006-01), p. 1440-1445
    Details
    In: Scandinavian Journal of Gastroenterology, Informa UK Limited, Vol. 41, No. 12 ( 2006-01), p. 1440-1445
    Type of Medium: Online Resource
    ISSN: 0036-5521 , 1502-7708
    URL: Article
    DOI: 10.1080/00365520600735696
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2006
    detail.hit.zdb_id: 1492631-3
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  • 5
    Online Resource
    Online Resource
    Dual angiotensin receptor and neprilysin inhibitor reduced portal pressure through peripheral vasodilatation and decreasing systemic arterial pressure in cirrhotic rats
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Journal of the Chinese Medical Association Vol. 86, No. 9 ( 2023-09), p. 786-794
    Details
    In: Journal of the Chinese Medical Association, Ovid Technologies (Wolters Kluwer Health), Vol. 86, No. 9 ( 2023-09), p. 786-794
    Abstract: Portal hypertension develops along with the progression of liver cirrhosis. Natriuretic peptides have been shown to reduce portal pressure but concomitantly activate the renin-angiotensin-aldosterone system (RAAS). Angiotensin receptor-neprilysin inhibitors (ARNIs) upregulate natriuretic peptides and avoid the adverse effects of RAAS activation. ARNIs have been shown to reduce portal pressure in rats with pre-hepatic portal hypertension, which involves relatively little liver injury. This study aimed to evaluate the relevant effects of an ARNI in rats with both liver cirrhosis and portal hypertension. Methods: Male Sprague-Dawley rats received common bile duct ligation to induce liver cirrhosis and portal hypertension. Sham-operated rats served as surgical controls. All rats were randomly allocated into three groups to receive distilled water (vehicle), LCZ696 (an ARNI), or valsartan for 4 weeks. Portal hypertension and relevant derangements were assessed after treatment. Results: Portal hypertension and hyperdynamic circulation developed in the cirrhotic rats. In the rats with cirrhosis and portal hypertension, both LCZ696 and valsartan reduced portal hypertension, mean arterial pressure, and systemic vascular resistance. The decrease in portal pressure was highly associated with the reduction in arterial pressure and systemic vascular resistance. Blood flow in hepatic, splanchnic, and portosystemic collateral systems was not altered. LCZ696 did not significantly influence liver injury or plasma cytokine levels. Liver fibrosis and splanchnic angiogenesis were not affected. Conclusion: ARNI treatment exerted portal pressure lowering effects via peripheral vasodilatation and decreasing systemic arterial pressure in the rats with liver cirrhosis and portal hypertension. Caution should be taken when using ARNIs in liver cirrhosis.
    Type of Medium: Online Resource
    ISSN: 1726-4901
    URL: Article
    DOI: 10.1097/JCMA.0000000000000959
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2202774-9
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  • 6
    Online Resource
    Online Resource
    Microbiota transplants from feces or gut content attenuated portal hypertension and portosystemic collaterals in cirrhotic rats
    Portland Press Ltd. ; 2021
    In:  Clinical Science Vol. 135, No. 24 ( 2021-12-22), p. 2709-2728
    Details
    In: Clinical Science, Portland Press Ltd., Vol. 135, No. 24 ( 2021-12-22), p. 2709-2728
    Abstract: Liver cirrhosis and portal hypertension is the end of chronic liver injury with hepatic, splanchnic and portosystemic collateral systems dysregulation. Liver injury is accompanied by gut dysbiosis whereas dysbiosis induces liver fibrosis, splanchnic angiogenesis and dysregulated vascular tones vice versa, making portal hypertension aggravated. It has been proved that intestinal microbiota transplantation alleviates dysbiosis. Nevertheless, the influences of microbiota transplantation on cirrhosis-related portal hypertension are not so clear. Liver cirrhosis with portal hypertension was induced by bile duct ligation (BDL) in rats. Sham rats were surgical controls. Rats randomly received vehicle, fecal or gut (terminal ileum) material transplantation. The results showed that microbiota transplantation from feces or gut material significantly reduced portal pressure in cirrhotic rats (P=0.010, 0.044). Hepatic resistance, vascular contractility, fibrosis and relevant protein expressions were not significantly different among cirrhotic rats. However, microbiota transplantation ameliorated splanchnic hyperdynamic flow and vasodilatation. Mesenteric angiogenesis, defined by whole mesenteric window vascular density, decreased in both transplantation groups and phosphorylated endothelial nitric-oxide synthase (eNOS) was down-regulated. Portosystemic shunts determined by splenorenal shunt (SRS) flow decreased in both transplantation groups (P=0.037, 0.032). Shunting severity assessed by microsphere distribution method showed consistent results. Compared with sham rats, cirrhotic rats lacked Lachnospiraceae. Both microbiota transplants increased Bifidobacterium. In conclusion, microbiota transplantation in cirrhotic rats reduced portal pressure, alleviated splanchnic hyperdynamic circulation and portosystemic shunts. The main beneficial effects may be focused on portosystemic collaterals-related events, such as hepatic encephalopathy and gastroesophageal variceal hemorrhage. Further clinical investigations are mandatory.
    Type of Medium: Online Resource
    ISSN: 0143-5221 , 1470-8736
    URL: Article
    DOI: 10.1042/CS20210602
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2021
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  • 7
    Online Resource
    Online Resource
    α-Adrenergic blockade prevented environmental temperature reduction-induced transient portal pressure surge in cirrhotic and portal hypertensive rats
    Portland Press Ltd. ; 2022
    In:  Clinical Science Vol. 136, No. 20 ( 2022-10-28), p. 1449-1466
    Details
    In: Clinical Science, Portland Press Ltd., Vol. 136, No. 20 ( 2022-10-28), p. 1449-1466
    Abstract: Exposure to low temperatures has been associated with increased gastroesophageal variceal bleeding in patients with cirrhosis and portal hypertension; however, the mechanism remains unclear. Therefore, the aim of the present study was to evaluate the impact of environmental temperature reduction on portal hypertension and the role of adrenergic signaling pathways in this phenomenon. Male Sprague-Dawley rats underwent common bile duct ligation or partial portal vein ligation to induce liver cirrhosis and/or portal hypertension. The impacts of acute or chronic changes in environmental temperature were surveyed. The results showed that acute cooling from 25 to 15°C and 5°C increased the portal pressure by 10.6% and 15.5% in cirrhotic rats, and by 22.2% and 36.1% in portal hypertensive rats, respectively. The transient portal pressure surge started shortly after cooling, reached a peak within 5 min and returned to baseline after 10 min. Systemic vascular resistance, mean arterial pressure and splanchnic blood flow increased significantly at the same time. Plasma epinephrine and norepinephrine concentrations, phospholipase C, protein kinase C activity and myosin phosphorylation of peripheral arteries increased significantly in response to cooling. Phentolamine (an α-blocker) but not propranolol (a non-selective β-blocker) dose-dependently inhibited the transient portal pressure surge and aforementioned molecular changes. In conclusion, environmental temperature reduction induced peripheral vasoconstriction via α-adrenergic pathways, and redistribution of blood flow to the splanchnic system led to a surge in transient portal pressure. Treatment with α-adrenergic receptor antagonists may exert additional benefits in controlling portal hypertension, especially on exposure to low temperatures.
    Type of Medium: Online Resource
    ISSN: 0143-5221 , 1470-8736
    URL: Article
    DOI: 10.1042/CS20220290
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2022
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  • 8
    Online Resource
    Online Resource
    Effects of PCSK-9 Inhibition by Alirocumab Treatments on Biliary Cirrhotic Rats
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 13 ( 2022-07-02), p. 7378-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 13 ( 2022-07-02), p. 7378-
    Abstract: Hyperlipidemia and oxidative stress with elevated oxidized low-density lipoprotein (ox-LDL) exacerbate hepatic inflammation and fibrosis. The plasma level of low-density lipoprotein (LDL) is controlled by proprotein convertase subtilisin/kexin 9 (PCSK9). Alirocumab is a monoclonal antibody that decreases LDL via inhibiting PCSK9 function. Apart from lipid-lowering effects, alirocumab exerts anti-inflammation, anti-angiogenesis and anti-oxidant effects. This study aims to investigate the impact of alirocumab treatment on common bile duct ligation (BDL)-induced biliary cirrhotic rats. After a 4-week treatment of alirocumab, the hemodynamic data, blood biochemistry, ox-LDL level, oxidative stress markers, severity of hepatic encephalopathy and abnormal angiogenesis of BDL rats were measured and compared to the control group. BDL rats presented cirrhotic pictures and elevated ammonia, total cholesterol, LDL and ox-LDL levels compared to the control group. Alirocumab decreased plasma levels of total cholesterol, LDL, and oxidative stress markers; however, it did not affect the hemodynamics, liver and renal biochemistry, and the plasma levels of ammonia and ox-LDL. The motor activities, portal-systemic collaterals and mesenteric vascular density were not significantly different between alirocumab-treated and control groups. In addition, it did not affect hepatic inflammation, intrahepatic angiogenesis, liver fibrosis and free cholesterol accumulation in the liver of BDL rats. In conclusion, PCSK9 inhibition by alirocumab treatment ameliorates hyperlipidemia and systemic oxidative stress in biliary cirrhotic rats. However, it does not affect the plasma level of ox-LDL, intrahepatic inflammation and fibrosis. In addition, PCSK9 inhibition has a neutral effect on abnormal angiogenesis and hepatic encephalopathy in biliary cirrhotic rats.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23137378
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 9
    Online Resource
    Online Resource
    NAFLD Aggravates Septic Shock Due to Inadequate Adrenal Response and 11β-HSDs Dysregulation in Rats
    MDPI AG ; 2020
    In:  Pharmaceutics Vol. 12, No. 5 ( 2020-04-28), p. 403-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 12, No. 5 ( 2020-04-28), p. 403-
    Abstract: Background: Non-alcoholic fatty liver disease (NAFLD) is linked with metabolic syndrome. Previous studies showed that obesity may disrupt adrenal function and adversely affect its counter-regulations against shock. This study hence evaluated adrenal function abnormalities in NAFLD with shock. Methods: Sprague-Dawley rats were fed with regular chow-diet (control) or high fat diet (HFD, 60% energy derived from fat). Blood tests were performed at the end of the 4th, 6th and 8th week, respectively. Experiments were performed at the end of the 8th week. Results: HFD rats developed NAFLD. HFD rats had 27% and 51% increase in plasma corticosterone at the 6th and 8th week in usual status. However, HFD rats had 5 times more reduction of mean arterial pressure in response to lipopolysaccharide-induced sepsis as compared to control rats. The corticosterone increment ratio was also lower in HFD rats, even after ACTH administration. 11β-HSD system tended to generate more corticosterone in HFD rats under hemodynamic stable status without shock and the trend was lost in HFD rats with septic shock. Conclusion: Rats with NAFLD had profound septic shock due to inadequate corticosterone response. This is, at least partly, due to 11β-HSDs dysregulation in sepsis.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics12050403
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 10
    Online Resource
    Online Resource
    Lycopene treatment improves intrahepatic fibrosis and attenuates pathological angiogenesis in biliary cirrhotic rats
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Journal of the Chinese Medical Association Vol. 85, No. 4 ( 2022-04), p. 414-420
    Details
    In: Journal of the Chinese Medical Association, Ovid Technologies (Wolters Kluwer Health), Vol. 85, No. 4 ( 2022-04), p. 414-420
    Abstract: Liver cirrhosis is characterized by liver fibrosis and pathological angiogenesis, which results in hyperdynamic circulation, portal-systemic collateral vascular formation, and abnormal angiogenesis. Lycopene is a nutrient mostly found in tomatoes. The beneficial effects of lycopene include anti-inflammation, anti-oxidation, anti-fibrosis, and anti-angiogenesis; however, the association between liver cirrhosis and pathological angiogenesis has yet to be studied. This study aimed to investigate the effects of lycopene on biliary cirrhotic rats. Methods: The efficacy of lycopene treatment in common bile duct ligation (BDL)-induced biliary cirrhotic rats was evaluated. Sham-operated rats served as surgical controls. Lycopene (20 mg/kg/day, oral gavage) or vehicle was administered to BDL or sham-operated rats for 4 weeks, after which the hemodynamics, liver biochemistry, portal-systemic shunting, liver and mesenteric angiogenesis, and hepatic angiogenesis-related protein expressions were examined. Results: Lycopene alleviated hyperdynamic circulation as evidenced by decreased cardiac index and increased peripheral vascular resistance ( p 〈 0.05), but it did not affect portal pressure or liver biochemistry in the BDL rats ( p 〉 0.05). Lycopene significantly diminished the shunting degree of portal-systemic collaterals ( p = 0.04) and mesenteric vascular density ( p = 0.01), and also ameliorated intrahepatic angiogenesis and liver fibrosis. In addition, lycopene upregulated endothelial nitric oxide synthase, protein kinase B (Akt) and phosphatidylinositol 3-kinases (PI3K), and downregulated vascular endothelial growth factor receptor 2 (VEGFR-2) protein expressions ( p 〈 0.05) in the livers of the BDL rats. Conclusion: Lycopene ameliorated liver fibrosis, hyperdynamic circulation, and pathological angiogenesis in biliary cirrhotic rats, possibly through the modulation of intrahepatic Akt/PI3K/eNOS and VEGFR-2 pathways.
    Type of Medium: Online Resource
    ISSN: 1726-4901
    URL: Article
    DOI: 10.1097/JCMA.0000000000000699
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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