QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal 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 Google Scholar Google Scholar Articles by Patel, N. S. A. Articles by Thiemermann, C. Search for Related Content PubMed PubMed Citation Articles by Patel, N. S. A. Articles by Thiemermann, C.

Reduction of Renal Ischemia-Reperfusion Injury in 5-Lipoxygenase Knockout Mice and by the 5-Lipoxygenase Inhibitor Zileuton

Centre for Experimental Medicine, Nephrology & Critical Care, William Harvey Research Institute, Queen Mary–University of London, United Kingdom (N.S.A.P., C.T.); Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Italy (S.C., R.D.P.); Department of Pharmacology, School of Pharmacy and Biomolecular Sciences, University of Brighton, United Kingdom (P.K.C.); Department of Experimental Pharmacology, University Federico II, Naples, Italy (L.S.); and Department of Veterinary and Agricultural Science, University of Teramo, Italy (D.B.)

The role of 5-lipoxygenase (5-LOX) in the pathophysiology of renal ischemia/reperfusion (I/R) injury is not known. Here we investigate the effects of 1) the 5-LOX inhibitor zileuton and 2) 5-LOX gene knockout (5-LOX^–/–) mice on renal dysfunction and injury caused by I/R of the kidney in mice. Wild-type mice treated with zileuton (3 mg/kg i.v.) or 5-LOX^–/– mice were subjected to bilateral renal artery occlusion (30 min) followed by reperfusion (24 h). Plasma urea, creatinine, and aspartate aminotransferase (AST) were measured as markers of renal dysfunction and reperfusion injury. Kidneys were used for histological evaluation of renal injury. Renal myeloperoxidase activity was measured and used as an indicator of polymorphonuclear leukocyte (PMN) infiltration and renal expression of intercellular adhesion molecule-1 (ICAM-1) was determined using immunohistochemistry. Administration of zileuton before I/R significantly reduced the degree of renal dysfunction (urea, creatinine) and injury (AST, histology). In addition, zileuton reduced the expression of ICAM-1 and the associated PMN infiltration caused by I/R of the mouse kidney. Compared with wild-type mice, the degree of renal dysfunction, injury, and inflammation caused by I/R in 5-LOX^–/– mice was also significantly reduced, confirming the pathophysiological role of 5-LOX in the development of renal I/R injury. We propose that 1) endogenous 5-LOX metabolites enhance the degree of renal injury, dysfunction, and inflammation caused by I/R of the kidney by promoting the expression of adhesion molecules, and 2) inhibitors of 5-LOX may be useful in the treatment of conditions associated with I/R of the kidney.

Address correspondence to: Prof. C. Thiemermann, Centre for Experimental Medicine, Nephrology & Critical Care, William Harvey Research Institute, Queen Mary - University of London, Charterhouse Square, London, EC1M 6BQ. E-mail: c.thiemermann{at}qmul.ac.uk

This article has been cited by other articles:

				M. U. Norman, S. Hulliger, P. Colarusso, and P. Kubes Multichannel Fluorescence Spinning Disk Microscopy Reveals Early Endogenous CD4 T Cell Recruitment in Contact Sensitivity via Complement J. Immunol., January 1, 2008; 180(1): 510 - 521. [Abstract] [Full Text] [PDF]

				T. Takajo, K. Tsuchida, T. Murahashi, K. Ueno, and I. Koshiishi Intramolecular rearrangement of linolenate peroxyl radicals in lipoxygenase reactions at lower oxygen content J. Lipid Res., April 1, 2007; 48(4): 855 - 862. [Abstract] [Full Text] [PDF]

				N. S.A. Patel, U. Cortes, R. Di Poala, E. Mazzon, H. Mota-Filipe, S. Cuzzocrea, Z.-Q. Wang, and C. Thiemermann Mice Lacking the 110-kD Isoform of Poly(ADP-Ribose) Glycohydrolase Are Protected against Renal Ischemia/Reperfusion Injury J. Am. Soc. Nephrol., March 1, 2005; 16(3): 712 - 719. [Abstract] [Full Text] [PDF]

				M. Collin, A. Rossi, S. Cuzzocrea, N. S. A. Patel, R. Di Paola, J. Hadley, M. Collino, L. Sautebin, and C. Thiemermann Reduction of the multiple organ injury and dysfunction caused by endotoxemia in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton J. Leukoc. Biol., November 1, 2004; 76(5): 961 - 970. [Abstract] [Full Text] [PDF]