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This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/F778    most recent 00215.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (30) Citing Articles via Google Scholar Google Scholar Articles by Adin, C. A. Articles by Agarwal, A. Search for Related Content PubMed PubMed Citation Articles by Adin, C. A. Articles by Agarwal, A.

Protective effects of exogenous bilirubin on ischemia-reperfusion injury in the isolated, perfused rat kidney

¹Department of Small Animal Clinical Sciences, Veterinary Medical Teaching Hospital, University of Florida, Gainesville; ²Department of Pathology, Immunology and Laboratory Medicine, Malcolm Randall Veterans Affairs Medical Center, Pathology and Laboratory Medical Service, Gainesville; and ³Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama

Submitted 9 June 2004 ; accepted in final form 19 November 2004

Heme oxygenase-1 (HO-1) is induced as an adaptive and protective response to tissue injury. HO-1 degrades heme into carbon monoxide (CO) and biliverdin; the latter is then converted to bilirubin. These reaction products have powerful antiapoptotic and antioxidant effects. Manipulation of the HO-1 system by administration of micromolar doses of exogenous CO or bilirubin has been performed in several organ systems, but the dose-related effects of these reaction products have not been investigated in the kidney. The purpose of this study was to evaluate the efficacy and dose-related protective effects of 1 or 10 µM bilirubin flush before a 20-min period of warm ischemia. In an effort to minimize interactions with other chemical messengers or organ systems, we elected to use an isolated, perfused rat kidney model with an acellular, oxygenated perfusate. Using this model, we demonstrated that bilirubin treatment resulted in significant improvements in renal vascular resistance, urine output, glomerular filtration rate, tubular function, and mitochondrial integrity after ischemia-reperfusion injury (IRI). Beneficial effects on organ viability were achieved most consistently with a dose of 10 µM bilirubin. We conclude that the protective effects of HO-1 activity during IRI in the kidney are mediated, at least in part, by bilirubin and that pretreatment with micromolar doses of bilirubin may offer a simple and inexpensive method to improve renal function after IRI.

isolated; perfused kidney; heme oxygenase-1

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