MnTMPyP, a cell-permeant SOD mimetic, reduces oxidative stress and apoptosis following renal ischemia-reperfusion.

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.

• Authors: Huan Ling Liang, Gail Hilton, Jordan Mortensen, Kevin Regner, Christopher P Johnson, Vani Nilakantan
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 296 Issue 2 Pg. F266-76 (Feb 2009) ISSN: 1931-857X [Print] United States
• PMID: 19091787 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antioxidants
• Metalloporphyrins
• Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin
• Tumor Necrosis Factor-alpha
• Superoxides
• 3-nitrotyrosine
• Tyrosine
• Creatinine
• Superoxide Dismutase
• Caspase 3

Topics

• Animals
• Antioxidants (metabolism)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Creatinine (blood)
• Gene Expression (drug effects)
• Kidney (pathology)
• Kidney Diseases (pathology, prevention & control)
• Kidney Function Tests
• Lipid Peroxidation (drug effects)
• Male
• Metalloporphyrins (pharmacology, therapeutic use)
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (metabolism, pathology, prevention & control)
• Superoxide Dismutase (metabolism)
• Superoxides (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Tyrosine (analogs & derivatives, biosynthesis)