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
12/19/2008Pubmed ID
19091787Pubmed Central ID
PMC2643863DOI
10.1152/ajprenal.90533.2008Scopus ID
2-s2.0-60549097415 (requires institutional sign-in at Scopus site) 66 CitationsAbstract
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 VAuthors
Christopher P. Johnson MD Professor in the Surgery department at Medical College of WisconsinKevin R. Regner MD Interim Chair, Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAntioxidants
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