Time-dependant protective effects of mangenese(III) tetrakis (1-methyl-4-pyridyl) porphyrin on mitochondrial function following renal ischemia-reperfusion injury

• Published in: Free radical research Vol. 44; no. 7; pp. 773 - 782
• Main Authors: Nilakantan, Vani, Liang, Huan Ling, Rajesh, Seenivasan, Mortensen, Jordan, Chandran, Karunakaran
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS) 01.07.2010; Taylor & Francis
• Subjects: Aconitate Hydratase - analysis; Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; apoptosis; Apoptosis - drug effects; Carrier Proteins - analysis; Caspase 3 - analysis; Cytochromes c - analysis; Drug Evaluation, Preclinical; Electron Spin Resonance Spectroscopy; EPR; Heme - analysis; In Situ Nick-End Labeling; Kidney - blood supply; Male; Metalloporphyrins - pharmacology; Metalloporphyrins - therapeutic use; mitochondria; Mitochondria - drug effects; Mitochondria - physiology; Mitochondrial Proteins - analysis; MnTMPyP; Oxidation-Reduction; Oxidative Stress - drug effects; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Renal ischemia-reperfusion; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; superoxide; Superoxide Dismutase - analysis; Time Factors
• ISSN: 1071-5762; 1029-2470; 1029-2470
• DOI: 10.3109/10715761003786164

Abstract This study examined the time-dependent effects of a cell permeable SOD mimetic, MnTMPyP, on mitochondrial function in renal ischemia-reperfusion injury (IRI). Male SD rats were subject to either sham operation or bilateral renal ischemia for 45 min followed by reperfusion for 1, 4 or 24 h. A sub-set of animals was treated with either saline vehicle or 5 mg/Kg of MnTMPyP (i.p.). EPR measurements showed that at 1-h reperfusion MnTMPyP prevented a decrease in aconitase activity (p < 0.05) and attenuated the increase in the high spin heme at g = 6 and oxidation of 4Fe4S to 3Fe4S signal at g = 2.015 (p < 0.01). MnTMPyP was effective in preventing loss of mitochondrial complexes and prevented the loss of cytochrome c and Smac/Diablo from mitochondria early in reperfusion. Following 24 h of reperfusion MnTMPyP was effective in attenuating caspase-3 and blocking apoptosis (p < 0.05). In conclusion, MnTMPyP has biphasic effects in renal IRI, inhibiting mitochondrial dysfunction at the early phases of reperfusion and prevention of apoptosis following longer durations of reperfusion.