title: Depletion and repletion of Ca2+ in the perfused rat liver.
abstract: Repletion with Ca2+ often leads to damage of previously Ca(2+)-depleted hearts (the calcium paradox). The behavior of the liver under similar conditions is not well understood. With a perfused rat liver model, we examined liver cell damage and lipid peroxidation during Ca2+ depletion and repletion and used lucigenin-enhanced chemiluminescence as a measure of oxygen radicals. During 30 minutes of Ca2+ depletion, release of lactate dehydrogenase and thiobarbituric acid-reactive substance did not change significantly. When Ca2+ depletion was extended to 150 minutes, release of lactic acid dehydrogenase and thiobarbituric acid-reactive substance and tissue oxygen radical levels all increased progressively, accompanied by decrease in oxygen uptake. Ca2+ repletion after 30 minutes of Ca2+ depletion caused small increases in release of lactic acid dehydrogenase and thiobarbituric acid-reactive substance but significantly suppressed the changes described, compared with expression in depleted livers without Ca2+ repletion. There were large releases of sinusoidal glutathione and glutathione disulfide at the onset of Ca2+ depletion, which declined within 15 minutes. On Ca2+ repletion, sinusoidal glutathione level decreased to its baseline but glutathione disulfide level did not change significantly. During long-term Ca2+ depletion, sinusoidal glutathione level was significantly higher than baseline but glutathione disulfide level remained low. These results indicate that long-term Ca2+ depletion causes oxidative stress and liver damage. Ca(2+)-dependent release of sinusoidal glutathione appears to result from causes other than oxidative stress. There is no evidence for the calcium paradox in the liver; in fact, reexposure to Ca2+ protects the liver from the injury caused by Ca2+ depletion.
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania, School of Medicine, Philadelphia 19104-6089.
authors.forename: M
authors.initials: M
authors.lastname: Okuda
authors.forename: H C
authors.initials: HC
authors.lastname: Lee
authors.forename: B
authors.initials: B
authors.lastname: Chance
authors.forename: C
authors.initials: C
authors.lastname: Kumar
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D010084:Oxidation-Reduction; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013858:Thiobarbiturates / Q000378:metabolism; D013997:Time Factors
chemical_list: D013858:Thiobarbiturates; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D002118:Calcium; D019803:Glutathione Disulfide