A Pastor

Publications (3)21.05 Total impact

• Article: Factors influencing the inhibition of biliary glutathione efflux induced by biliary obstruction.

  A Pastor, P S Collado, J González-Gallego
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  ABSTRACT: The aim of this study was to investigate mechanisms responsible for the inhibition of biliary glutathione efflux in rats with secondary biliary cirrhosis. Rats were studied after bile duct obstruction for 28 days. The biliary secretion of reduced glutathione (GSH), oxidised glutathione (GSSG) and cysteine were completely inhibited in biliary obstructed rats. Hepatic gamma glutamyltranspeptidase (gamma-GT) activity increased significantly, but following its inhibition by acivicin administration GSH, GSSG and cysteine were still absent in bile. Biliary obstruction resulted in a significant increase of the permeability of the paracellular pathway, as shown by the higher bile/plasma ratio and hepatic clearance of [14C]sucrose. GSH and GSSG were, however, significantly lower in the carotid artery and hepatic vein of obstructed animals and the arteriovenous difference across the liver was reduced. The concentration of GSH was significantly reduced and that of GSSG increased in the liver of obstructed rats. Biliary obstruction induced an increase in the hepatic concentration of cysteine and an inhibition of both gamma glutamylcysteine synthetase and methionine adenosyl transferase activities. Dichlorofluorescein (DCF) and the GSSG/GSH ratio and thiobarbituric acid reactive substances (TBARS) concentration, markers of reactive oxygen species production and lipid peroxidation, respectively, were significantly increased. Our data indicate that increased degradation or blood reflux of glutathione do not participate in the disruption of its secretion into bile and support the view that impairment of glutathione synthesis and oxidative stress could contribute to the decline in biliary glutathione output.
  Life Sciences 12/2000; 68(1):69-79. · 2.53 Impact Factor
• Source

  Available from: ufrgs.br

  Article: Antioxidant enzyme status in biliary obstructed rats: effects of N-acetylcysteine.

  A Pastor, P S Collado, M Almar, J González-Gallego
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  ABSTRACT: N-acetylcysteine (NAC) is a modulator of thiol levels that protects against hepatotoxic agents. The aim of this study was to investigate whether NAC might improve hepatic antioxidant defenses in chronically biliary obstructed rats. Secondary biliary cirrhosis was induced by 28 days of bile-duct obstruction. Groups of control and cirrhotic animals received NAC (50 mumol .kg-1.d-1 i.m.) through the experimental period. Bile-duct obstruction resulted in decreased liver glutathione concentrations. Dichlorofluorescein (DCF) and thiobarbituric acid reactive substances (TBARS) concentrations, measured as markers of production of reactive oxygen species and lipid peroxidation, respectively, were significantly increased. Microsomal and mitochondrial membrane fluidity and the activities of catalase, cytosolic and mitochondrial superoxide dismutase (SOD), glutathione S-transferase, and cytosolic and mitochondrial Se-dependent and Se-independent glutathione peroxidase (GPx) were significantly reduced. NAC corrected the reduction in glutathione concentration and partially prevented the increases in DCF and TBARS concentrations. In addition, NAC treatment resulted in significant preservation of membrane fluidity and of the activities of catalase, mitochondrial SOD and the different forms of GPx. Our data indicate that NAC maintains antioxidant defenses in biliary obstructed rats. These effects of NAC suggest that it may be a useful agent to preserve liver function in patients with biliary obstruction.
  Journal of Hepatology 09/1997; 27(2):363-70. · 9.26 Impact Factor
• Source

  Available from: ufrgs.br

  Article: Microsomal function in biliary obstructed rats: effects of S-adenosylmethionine.

  A Pastor, P S Collado, M Almar, J González-Gallego
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  ABSTRACT: S-adenosylmethionine has been reported to have beneficial effects in the treatment of different chronic liver diseases and to protect against different hepatotoxic agents. The aim of this study was to investigate whether S-adenosylmethionine treatment might contribute to improved microsomal function in chronically biliary obstructed rats. Secondary biliary cirrhosis was induced by 28 days of bile duct obstruction. Groups of control and cirrhotic animals received S-adenosylmethionine (10 mg/kg per day) through the experimental period. Bile duct obstruction resulted in a marked increase in lipid peroxidation levels and decreases in glutathione concentration, microsomal membrane fluidity, microsomal cytochrome P-450 content, NADPH-cytochrome P-450 reductase activity and the activities of the aniline hydroxylase, aminopyrine demethylase and ethoxycoumarin deethylase. Reductions in glutathione and cytochrome P-450 concentration were not corrected by S-adenosylmethionine, but lipid peroxidation, the decrease in the activities of the various microsomal monooxygenases and the reduction in microsomal membrane fluidity were partially prevented. A significant relationship was found between membrane fluidity and aniline hydroxylase, aminopyrine demethylase or ethoxycoumarin deethylase activities. S-adenosylmethionine administration partially preserves microsomal function. This effect could be associated to the protection of membrane function by restoring transmethylation reactions.
  Journal of Hepatology 04/1996; 24(3):353-9. · 9.26 Impact Factor