Impaired Renal Function in Obstructive Jaundice: Roles of the Thromboxane and Endothelin Systems

Kramer, Herbert J.

doi:10.1159/000190241

Cited by 28 publications

(19 citation statements)

References 45 publications

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“…Extrahepatic cholestasis induces a complex series of hormonal changes in kidneys, [1][2][3][4] which might influence the regulation of OAT1 and OAT3. Likely several local and systemic factors are produced at the same time, and the role of such factors in the regulation of channels and transporters in the presence of BDL is unknown.…”

Section: Discussionmentioning

confidence: 99%

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Expression of rat renal cortical OAT1 and OAT3 in response to acute biliary obstruction

et al. 2006

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Renal function in the course of obstructive jaundice has been the subject of great interest; however, little is known about the expression of renal organic anion transporters. The objective of this work was to study, in rats with acute extrahepatic cholestasis, the cortical renal expression of the organic anion transporter 1 (OAT1) and the organic anion transporter 3 (OAT3), in association with the pharmacokinetics and renal excretion of furosemide (FS). Male Wistar rats underwent bile duct ligation (BDL rats). Pair-fed sham-operated rats served as controls. All studies were carried out 21 hours after surgery. Rats were anesthetized and the pharmacokinetic parameters of FS and the renal elimination of FS were determined. Afterwards, the kidneys were excised and processed for immunoblot (basolateral membrane and renal homogenates) or immunocytochemical (light microscopic and confocal immunofluorescence microscopic analysis) techniques. The systemic and renal clearance of FS as well as the excreted and secreted load of FS increased in BDL rats. In kidneys from BDL rats, immunoblotting showed a significant increase in the abundance of both OAT1 and OAT3 in homogenates from renal cortex. In basolateral membranes from kidney cortex of BDL rats, OAT1 abundance was also increased and OAT3 abundance was not modified. Immunocytochemical techniques confirmed these results. In conclusion, acute obstructive jaundice is associated with an upregulation of OAT1 and OAT3, which might explain, at least in part, the increased systemic and renal elimination of FS. (HEPATOLOGY 2006;43:1092-1100

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Section: Discussionmentioning

confidence: 99%

“…Extrahepatic cholestasis refers to obstruction of large bile ducts outside the liver, for instance, due to gallstones. [1][2][3][4] Kidney and liver eliminate numerous potentially toxic xenobiotics, including drugs, toxins, and endogenous metabolites. In some cases, the loss of one route of elimination can be compensated for by the other.…”

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confidence: 99%

Expression of rat renal cortical OAT1 and OAT3 in response to acute biliary obstruction

et al. 2006

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“…tubular brush border vesicles 16,18 , which also could represent one of the mechanisms for decreased fluid and sodium reabsorption in proximal and also in distal nephrons segment 18 . Rodrigo et al 19 suggested that the renal compromise of obstructive jaundice is characterized by changes in the tubular handling of electrolytes.…”

Section: Renal Morphologymentioning

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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“…In some cases, the loss of one route of elimination can be compensated by another [24][25][26] . It must also be mentioned that impairment of liver or kidney functions can cause syndromes characterized by injury of the alternative elimination organ [24,27,28] . For example, prolonged cholestasis, characterized by retention of bile compound, may cause renal damage (reduction in renal hemodynamics, impairment of renal excretion of water and salts, and sensitization of the kidney to anoxia damage), which sometimes leads to renal failure.…”

Section: Cholestasis and Renal Damagementioning

confidence: 99%

Renal elimination of organic anions in cholestasis

Torres¹

2008

WJG

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The disposition of most drugs is highly dependent on specialized transporters. OAT1 and OAT3 are two organic anion transporters expressed in the basolateral membrane of renal proximal tubule cells, identified as contributors to xenobiotic and endogenous organic anion secretion. It is well known that cholestasis may cause renal damage. Impairment of kidney function produces modifications in the renal elimination of drugs. Recent studies have demonstrated that the renal abundance of OAT1 and OAT3 plays an important role in the renal elimination of organic anions in the presence of extrahepatic cholestasis. Time elapsed after obstructive cholestasis has an important impact on the regulation of both types of organic anion transporters. The renal expression of OAT1 and OAT3 should be taken into account in order to improve pharmacotherapeutic efficacy and to prevent drug toxicity during the onset of this hepatic disease.

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Impaired Renal Function in Obstructive Jaundice: Roles of the Thromboxane and Endothelin Systems

Cited by 28 publications

References 45 publications

Expression of rat renal cortical OAT1 and OAT3 in response to acute biliary obstruction

Expression of rat renal cortical OAT1 and OAT3 in response to acute biliary obstruction

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

Renal elimination of organic anions in cholestasis

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