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This Article Full Text Full Text (PDF) All Versions of this Article: 292/2/F888    most recent 00064.2006v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Kirkby, K. Articles by Adin, C. Search for Related Content PubMed PubMed Citation Articles by Kirkby, K. Articles by Adin, C.

Intravenous bilirubin provides incomplete protection against renal ischemia-reperfusion injury in vivo

¹Comparative Nephrology and Transplantation Laboratory, Department of Small Animal Clinical Sciences, and ²Department of Physiology and Functional Genomics, University of Florida, Gainesville; ³Department of Medicine, Division of Nephrology, University of Alabama at Birmingham, Alabama; and ⁴Pathology and Laboratory Medical Services, Malcolm Randall Veterans Affairs Medical Center, Gainesville, Florida

Submitted 22 February 2006 ; accepted in final form 6 October 2006

Exogenous bilirubin (BR) substitutes for the protective effects of heme oxygenase (HO) in several organ systems. Our objective was to investigate the effects of exogenous BR in an in vivo model of ischemia-reperfusion injury (IRI) in the rat kidney. Four groups of male Sprague-Dawley rats were anesthetized using isoflurane in oxygen and treated with 1) 5 mg/kg intravenous (iv) BR, 1 h before ischemia and 6-h reperfusion; 2) vehicle 1 h before ischemia and 6-h reperfusion; 3) 20 mg/kg iv BR, 1 h before and during ischemia; and 4) vehicle 1 h before and during ischemia. Bilateral renal clamping (30 min) was followed by 6-h reperfusion. Infusion of 5 mg/kg iv BR achieved target levels in the serum at 6 h postischemia (31 ± 9 µmol/l). Infusion of 20 mg/kg BR reached 50 ± 22 µmol/l at the end of ischemia, and a significant improvement was seen in serum creatinine at 6 h (1.07 ± 28 vs. 1.38 ± 0.18 mg/dl, P = 0.043). Glomerular filtration rate, estimated renal plasma flow, fractional excretion of electrolytes, and renal vascular resistance were not significantly improved in BR-treated groups. Histological grading demonstrated a trend toward preservation of cortical proximal tubules in rats receiving 20 mg/kg iv BR compared with control; however, neither BR dose provided protection against injury to the renal medulla. At the doses administered, iv BR did not provide complete protection against IRI in vivo. Combined supplementation of both BR and carbon monoxide may be required to preserve renal blood flow and adequately substitute for the protective effects of HO in vivo.

heme oxygenase; carbon monoxide; biliverdin