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MnTMPyP, a cell-permeant SOD mimetic, reduces oxidative stress and apoptosis following renal ischemia-reperfusion. Am J Physiol Renal Physiol 2009 Feb;296(2):F266-76

Date

12/19/2008

Pubmed ID

19091787

Pubmed Central ID

PMC2643863

DOI

10.1152/ajprenal.90533.2008

Scopus ID

2-s2.0-60549097415   55 Citations

Abstract

Oxidative stress and apoptosis are important factors in the etiology of renal ischemia-reperfusion (I/R) injury. The present study tested the hypothesis that the cell-permeant SOD mimetic manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP) protects the kidney from I/R-mediated oxidative stress and apoptosis in vivo. Male Sprague-Dawley rats (175-220 g) underwent renal I/R by bilateral clamping of the renal arteries for 45 min followed by reperfusion for 24 h. To examine the role of reactive oxygen species (ROS) in renal I/R injury, a subset of animals were treated with either saline vehicle (I/R Veh) or MnTMPyP (I/R Mn) (5 mg/kg ip) 30 min before and 6 h after surgery. MnTMPyP significantly attenuated the I/R-mediated increase in serum creatinine levels and decreased tubular epithelial cell damage following I/R. MnTMPyP also decreased TNF-alpha levels, gp(91phox), and lipid peroxidation after I/R. Furthermore, MnTMPyP inhibited the I/R-mediated increase in apoptosis and caspase-3 activation. Interestingly, although MnTMPyP did not increase expression of the antiapoptotic protein Bcl-2, it decreased the expression of the proapoptotic genes Bax and FasL. These results suggest that MnTMPyP is effective in reducing apoptosis associated with renal I/R injury and that multiple signaling mechanisms are involved in ROS-mediated cell death following renal I/R injury.

Author List

Liang HL, Hilton G, Mortensen J, Regner K, Johnson CP, Nilakantan V

Authors

Christopher P. Johnson MD Professor in the Surgery department at Medical College of Wisconsin
Kevin R. Regner MD Chief, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antioxidants
Apoptosis
Caspase 3
Creatinine
Gene Expression
Kidney
Kidney Diseases
Kidney Function Tests
Lipid Peroxidation
Male
Metalloporphyrins
Oxidative Stress
Rats
Rats, Sprague-Dawley
Reperfusion Injury
Superoxide Dismutase
Superoxides
Tumor Necrosis Factor-alpha
Tyrosine
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00