title: Intravenous bilirubin provides incomplete protection against renal ischemia-reperfusion injury in vivo.
abstract: 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 micromol/l). Infusion of 20 mg/kg BR reached 50 +/- 22 micromol/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.
authors.affiliation: Comparative Nephrology and Transplantation Laboratory, Dept. of Small Animal Clinical Sciences, University of Florida, Gainesville, FL 32610-0126, USA. kirkbyk@mail.vetmed.ufl.edu
authors.forename: Kristin
authors.initials: K
authors.lastname: Kirkby
authors.forename: Chris
authors.initials: C
authors.lastname: Baylis
authors.forename: Anupam
authors.initials: A
authors.lastname: Agarwal
authors.forename: Byron
authors.initials: B
authors.lastname: Croker
authors.forename: Linda
authors.initials: L
authors.lastname: Archer
authors.forename: Christopher
authors.initials: C
authors.lastname: Adin
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000008:administration & dosage* / Q000097:blood; D001806:Blood Urea Nitrogen; D005919:Glomerular Filtration Rate; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D007674:Kidney Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014655:Vascular Resistance
chemical_list: D017392:Thiobarbituric Acid Reactive Substances; D001663:Bilirubin