Elevated glomerular and blood mononuclear lymphocyte nitric oxide production in rats with chronic bile duct ligation: Role of inducible nitric oxide synthase activation

Criado, M.; Flores, Olga; Ortiz, Mariela; Hidalgo, F.; Rodrı́guez-López, Ana M.; Eleno, Nélida; Atucha, Noemı́ M.; Sánchez‐Rodríguez, Ángel; Arévalo, Miguel; Garcı́a-Estañ, Joaquı́n; Jm, López-Novoa

doi:10.1002/hep.510260203

Cited by 49 publications

(43 citation statements)

References 51 publications

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“…There is still much controversy regarding the contribution of the different isoforms to the increased NO production in cirrhosis. Although iNOS mRNA levels are up-regulated in Kupffer cells, sinusoidal cells, 22 and lymphocytes 23 following bile duct ligation, this does not appear to be the case in blood vessels. However, eNOS mRNA levels have been found to be increased in aortas isolated from cirrhotic rats.…”

Section: Discussionmentioning

confidence: 86%

Lipoic acid prevents development of the hyperdynamic circulation in anesthetized rats with biliary cirrhosis

et al. 1999

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Chronic bile duct ligation is associated with the development of oxidant injury, biliary cirrhosis, portal hypertension, and a hyperdynamic circulation. We have previously demonstrated that the hyperdynamic circulation in the partial portal vein-ligated rat can be prevented by the administration of N-acetylcysteine. To extend these findings, we have examined the effect of lipoic acid, a thiolcontaining antioxidant, on hemodynamics, oxidative stress, and nitric oxide (NO) production in bile duct-ligated (BDL) cirrhotic rats. Lipoic acid was given continuously in drinking water to normal and BDL rats; control rats received ordinary drinking water, and animals were studied at 24 days following surgery. Lipoic acid prevented the development of the hyperdynamic circulation (cardiac index [CI]: 15.7 ؎ 2.0 vs. 29.5 ؎ 2.1 mL и min ؊1 и 100 g ؊1 ; P F .05) and significantly attenuated the rise in portal pressure (PP) (12.7 ؎ 0.8 vs. 15.2 ؎ 0.5 mm Hg; P F .05). Hepatic nitric oxide synthase (NOS) activity and plasma nitrite/nitrate concentration increased significantly following bile duct ligation, and both of these were prevented by lipoic acid. Lipoic acid had no effect on the biochemical or histological parameters of liver function in the cirrhotic group. We conclude that lipoic acid prevents the development of the hyperdynamic circulation in the rat model of biliary cirrhosis, and that this is associated with decreased synthesis of NO. (HEPATOLOGY 1999;29:1358-1363.)Chronic bile duct ligation leads to biliary cirrhosis within 3 to 4 weeks in the rat. Following bile duct ligation, there is cholestatic liver injury, with depletion of endogenous antioxidants 1,2 and increased levels of markers of oxidant injury. 1,3 This is followed by the development of ductular proliferation and fibrosis, and is associated with the development of portal hypertension and a hyperdynamic circulation, characterized by a high cardiac output and low systemic vascular resistance. Previous studies have shown protective effects of antioxidants on liver damage in this model as assessed by biochemical and histological parameters, 1,4,5 and also a moderate reduction in portal pressure (PP). 6 The hyperdynamic circulation that occurs in this model following the development of biliary cirrhosis is central to the development of many of the complications that occur in advanced liver disease, including ascites and renal dysfunction, portal hypertension, and the hepatopulmonary syndrome. We previously demonstrated that chronic administration of N-acetylcysteine prevents development of the hyperdynamic circulation following partial portal vein ligation 7 and is accompanied by decreased plasma concentrations of the metabolic products of nitric oxide (NO), nitrite and nitrate. However, in the above study, N-acetylcysteine was given twice daily by intraperitoneal injection, because it has a limited oral bioavailability. Therefore, to extend these studies to a cirrhotic model, we have used the sodium salt of lipoic acid, a thiol-containing antioxidant with g...

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Section: Discussionmentioning

confidence: 86%

Lipoic acid prevents development of the hyperdynamic circulation in anesthetized rats with biliary cirrhosis

et al. 1999

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“…The rats were subjected to either bile duct ligation (BDL) or sham operation using aseptic techniques, as previously described by Criado et al 12 . Group 1 rats (Sham-control, n=7) underwent laparotomy alone and bile duct was dissected from surrounding tissue.…”

Section: Methodsmentioning

confidence: 99%

Effect of sirolimus on renal injury induced by bile duct ligation in rats

et al. 2010

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Purpose:To evaluate the effects of sirolimus (SRL) on renal injury in rats with bile duct ligation. Methods: A total of 21 male Sprague-Dawley rats weighing 220-260g were used. Group 1 (Sham-control, n=7) rats were undergone laparotomy alone and bile duct was just dissected from the surrounding tissue. Group 2 rats (BDL/Untreated, n=7) were subjected to bile duct ligation and no drug was applied. Group 3 rats (BDL/SRL, n =7) received a daily dose of sirolimus (0.5 mg·day -1 ×kg -1 dissolved 1 ml in saline) by orogastric tube for 14 days after BDL. At the end of the two-week period, biochemical and histological evaluation were processed. Results: AST, ALT, AP and TB levels values were decreased in group 3 when compared to group 2. There was no significant difference in serum levels of BUN and creatinine among all the experimental groups. Histological evaluation of the liver of BDL/Untreated group rats demonstrated marked portal fibrosis and signs of major bile duct obstruction with prominent portal and lobular inflammation. In BDL/SRL group, moderate damage was seen. Tubular injury scores were higher in the BDL subgroups; however, group 3 rats showed considerably fewer lesions in the tubules and interstitium compared to the group 2 rats. In group 2 animals, in the epithelial cells of proximal tubules presented vacuoles and hydropic changes, atrophy and inflammatory cell infiltrate in the medullar interstitium. Conclusions: Sirolimus decreased tubulointerstitial lesions in kidney induced by bile duct ligation in rats. The improve effects of sirolimus on renal morphology can be due to improved liver function or due to direct action on the kidney. Key words: Sirolimus. Common Bile Duct. Ligation. Liver. Kidney. Rats. RESUMO Objetivo:Investigar os efeitos do sirolimo (SRL) na lesão renal induzida pela ligadura do ducto biliar em ratos. Métodos: Foram utilizados 21 ratos Sprague-Dawley pesando entre 220-260 g. Grupo 1 (Sham-controle, n=7) submetidos a laparotomia e o ducto biliar dissecado do tecido circundante. Grupo 2 (BDL/Não tratado, n=7) foram submetidos a ligadura do ducto biliar e nenhuma droga foi aplicada. Grupo 3 (BDL/SRL, n=7) receberam dose diária de sirolimo (0,5 mg dia -1 ×kg -1 dissolvido em 1 ml em solução salina) por tubo orogástrico por 14 dias após BDL. Após duas semanas era realizada avaliação bioquímica e histológica. Resultados: Níveis de AST, ALT, AP e TB estavam diminuídos no grupo 3 comparado ao grupo 2. Não houve diferença significante nos níveis séricos de BUN e creatinina em todos os grupos. Observou-se na avaliação histológica evidente fibrose portal e sinais de obstrução do ducto biliar com evidente inflamação portal e lobular. No grupo BDL/SRL verificou-se dano moderado. Lesão tubular foi maior nos subgrupos BDL; entretanto, o grupo 3 mostrou considerável menos lesões nos túbulos e interstício comparados ao grupo 2. No grupo 2 as células epiteliais dos túbulos proximais apresentaram vacúolos e alterações hidrópicas, atrofia e infiltrado celular inflamatório no interstício medula...

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“…After 48 hours, rats were anaesthetised with 2-2-2-tribromoethanol and, under aseptic techniques, subjected to either bile duct ligation (BDL) and excision or sham operation (SO), as previously described [37].…”

Section: Bile Duct Ligationmentioning

confidence: 99%

Endoglin Upregulation in the Liver after Bile Duct Ligation in Rats

Pérez‐Barriocanal¹

2011

TOGASJ

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Abstract:Background: Transforming growth factor beta 1 (TGF-1) has been implicated in the stimulation of extracellular matrix synthesis in acute and chronic liver disease. Endoglin (CD-105) is a membrane glycoprotein that binds TGF-1 with high affinity. Endoglin is overexpressed in several model of fibrosis. The goal of the present study was to evaluate the effect of bile duct ligation (BDL) on endoglin expression and the effect of endoglin overexpression on liver fibrosis in rats.Methods: Rat livers were transfected with a vector containing full length human endoglin (h-end) or an empty vector (mock) and 48 hours after were subjected to either BDL or sham operation (SO). Eighteen days after, a blood sample was obtained and bilirubin and serum enzyme activities were measured to assess liver damage. Liver fibrosis was quantified by a computer-assisted image analysis of Sirius red stained livers and by liver hydroxyproline content. Endoglin expression in the liver tissue was assessed by Western blot and immunohystochemistry.Results: Both immunohistochemistry and Western blot reveals endoglin upregulation after BDL in rats. In addition, these techniques also reveal effective human endoglin transfection in the rat's liver. After BDL, liver fibrosis and plasma levels of enzymes were similar in h-end transfected and mock-transfected rats. Western blots showed higher endoglin expression after BDL in h-end transfected and mock-transfected rats. Conclusions:The present study provides clear evidence that endoglin is upregulated in the liver of rats with BDL. h-end overexpression did not improve liver fibrosis after BDL in rats.

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Elevated glomerular and blood mononuclear lymphocyte nitric oxide production in rats with chronic bile duct ligation: Role of inducible nitric oxide synthase activation

Cited by 49 publications

References 51 publications

Lipoic acid prevents development of the hyperdynamic circulation in anesthetized rats with biliary cirrhosis

Lipoic acid prevents development of the hyperdynamic circulation in anesthetized rats with biliary cirrhosis

Effect of sirolimus on renal injury induced by bile duct ligation in rats

Endoglin Upregulation in the Liver after Bile Duct Ligation in Rats

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