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Abstract
Background. Liver ischemia/reperfusion is frequently associated with organ injury to which reactive
oxygen species contribute. The aim of our study was to evaluate cytosolic and mitochondrial
glutathione levels and morphological changes in hepatocytes of rat liver in an experimental
model of ischemia/reperfusion.
Materials and methods. The experimental procedure consisted of temporary interruption of blood flow to the
left lateral and medial hepatic lobes for different lengths of time and, in some cases,
subsequent reperfusion. Cytosolic and mitochondrial glutathione levels were evaluated
and ultrastructural analysis was carried out for all samples.
Results. Ischemic lobes showed ultrastructural changes in relationship with the increase in
ischemia time. Total glutathione levels did not show variations in ischemic lobes
and sham lobes with respect to control rats during ischemia only. Instead, during
reperfusion, significant ultrastructural alterations of the hepatocytes and a significant
depletion of glutatione in cytosolic and mitochondrial compartments were evident.
The sham lobes also showed a significant glutathione decrement. Increased oxidized
glutathione (GSSG) levels were found during ischemia both in ischemic lobes and in
sham lobes. During reperfusion GSSG was found to a minor extent, in the cytosolic
compartment. In mitochondria GSSG levels were also high during reperfusion.
Conclusions. We conclude that depletion of glutathione contributes to impaired liver after reperfusion
following ischemia but depletion of glutathione alone does not induce changes in the
morphology of the hepatocytes. Glutathione depletion and a greater quantity of GSSG,
even in sham lobes, may indicate a metabolic alteration which spreads to compartments
that are not involved in ischemia/reperfusion.
Keywords
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References
REFERENCES
- Liver ischemia for hepatic resection. Where is the limit.Surgery. 1992; 111: 251
- Involvement of platelet-activating factor in cytokine production and neutrophil activation after hepatic ischemia–reperfusion.Hepatology. 1996; 23: 1656
- Liver viability after ischemia–reperfusion.Arch. Surg. Chicago. 1991; 126: 767
- Oxygen-derived free radicals in post-ischemic tissue injury.N. Engl. J. Med. 1985; 312: 159
- Pharmacologic approach to tissue injury mediated by free radicals and other reactive oxygen metabolites.Am. J. Surg. 1991; 161: 488
- Ischemia–reperfusion injury.Br. J. Surg. 1994; 81: 637
- Involvement of hydrogen peroxide and hydroxyl radical in the “oxygen paradox”: Reduction of creatine kinase release by catalase, allopurinol or deferoxamine, but not by superoxide dismutase.J. Mol. Cell. Cardiol. 1985; 17: 675
- Cytochemical studies of hydrogen peroxide generation in post-ischemic hepatocytes.Am. J. Physiol. 1991; 260: H123
- Glutathione.Annu. Rev. Biochem. 1983; 52: 711
- Status of the mitochondrial pool of glutathione in the isolated hepatocyte.J. Biol. Chem. 1982; 257: 3747
- Hepatic mitochondrial and cytosolic glutathione content and the subcellular distribution of GSH-S-transferases.FEBS Lett. 1979; 97: 138
- An ultrastructural study of six cases of chronic active C hepatitis. A comparison with chronic active B hepatitis.Ultrastruct. Pathol. 1993; 17: 477
- Protein measurement with the Folin phenol reagent.J. Biol. Chem. 1951; 193: 265
- Assay of glutathione, glutathione disulfide and glutathione mixed disulphides in biological samples.Methods Enzymol. 1981; 77: 373
- The molecular and cellular basis of reperfusion injury following organ transplantation.Transplant. Rev. 1998; 12: 14
- Multiple-system organ damage resulting from prolonged hepatic inflow interruption.Arch. Surg. Chicago. 1996; 131: 442
- Study on hepatic injury and antioxidant enzyme activities in rat subcellular organelles following in vivo ischemia and reperfusion.Mol. Cell. Biochem. 1997; 176: 337
- The impact of ischemia/reperfusion injury on specific and non-specific. Early and late chronic events after organ transplantation.Transplant. Rev. 1996; 10: 108
- Glyoxalase II and glutathione levels in rat liver mitochondria during cold storage in Euro-Collins and University of Wisconsin solution.Transplantation. 1996; 61: 1416
- Oxidized glutathione as a marker of ischemia reperfusion associated with single lung transplantation.J. Am. Coll. Surg. 1995; 180: 25
- The mitochondrial permeability transition.Biochim. Biophys. Acta. 1995; 1241: 139
- Mitochondrial glutathione status during Ca2+ ionophore-induced injury to isolated hepatocytes.Arch. Biochem. Biophys. 1988; 263: 226
- Mitochondrial oxidative phosphorylation and intracellular glutathione compartmentation during rat liver regeneration.Hepatology. 1995; 21: 1450
- The relationship between mitochondrial membrane permeability, membrane potential, and the retention of Ca2+ by mitochondria.J. Biol. Chem. 1980; 255: 8663
- The oxidative inactivation of mitochondrial electron transport chain components and ATPase.J. Biol. Chem. 1990; 265: 16330
- Oxidative damage to mitochondrial DNA and glutathione oxidation in apoptosis: Studies in vivo and in vitro.FASEB J. 1999; 13: 1055
- Adenine nucleotide metabolism and its relation to organ viability in human liver transplantation.Transplantation. 1988; 45: 138
- Role of tumor necrosis factor-alpha in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat.J. Clin. Invest. 1990; 85: 1936
- Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation.J. Biol. Chem. 1992; 267: 5317
- Tumor necrosis factor increases hepatocellular glutathione by transcriptional regulation of the heavy subunit chain of gamma-glutamylcysteine synthetase.J. Biol. Chem. 1997; 272: 30371
- GSH transport in mitochondria: Defense against TNF-induced oxidative stress and alcohol-induced defect.Am. J. Physiol. 1997; 273
- ICAM-1 upregulation in distant tissues after hepatic ischemia/reperfusion: A clue to the mechanism of multiple organ failure.J. Pediatr. Surg. 1998; 33: 350
- Direct induction of acute lung and myocardial dysfunction by liver ischemia and reperfusion.J. Trauma. 1997; 43: 627
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© 2000 Academic Press. Published by Elsevier Inc. All rights reserved.