Manganese porphyrin reduces renal injury and mitochondrial damage during ischemia/reperfusion.
Renal ischemia/reperfusion (I/R) injury often occurs as a result of vascular surgery, organ procurement, or transplantation. We previously showed that renal I/R results in ATP depletion, oxidant production, and manganese superoxide dismutase (MnSOD) inactivation. There have been several reports that overexpression of MnSOD protects tissues/organs from I/R-related damage, thus a loss of MnSOD activity during I/R likely contributes to tissue injury. The present study examined the therapeutic benefit of a catalytic antioxidant, Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5+)), using the rat renal I/R model. This was the first study to examine the effects of MnTnHex-2-PyP(5+) in an animal model of oxidative stress injury. Our results showed that porphyrin pretreatment of rats for 24 h protected against ATP depletion, MnSOD inactivation, nitrotyrosine formation, and renal dysfunction. The dose (50 microg/kg) used in this study is lower than doses of various types of antioxidants commonly used in animal models of oxidative stress injuries. In addition, using novel proteomic techniques, we identified the ATP synthase-beta subunit as a key protein induced by MnTnHex-2-PyP(5+) treatment alone and complex V (ATP synthase) as a target of injury during renal I/R. These results showed that MnTnHex-2-PyP(5+) protected against renal I/R injury via induction of key mitochondrial proteins that may be capable of blunting oxidative injury.
Saba
Hamida
H
Department of Pharmacology/Toxicology, University of Arkansas for Medical Sciences, 325 Jack Stephens Drive, Biomedical Building I 323D, Little Rock, AR 72205, USA.
Batinic-Haberle
Ines
I
Munusamy
Shankar
S
Mitchell
Tanecia
T
Lichti
Cheryl
C
Megyesi
Judit
J
MacMillan-Crow
Lee Ann
LA
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D015180:Electrophoresis, Gel, Two-Dimensional; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008665:Metalloporphyrins; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation
D000975:Antioxidants; D008665:Metalloporphyrins; D024101:Mitochondrial Proteins; C521294:Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin; D013482:Superoxide Dismutase