Manganese porphyrin reduces renal injury and mitochondrial damage during ischemia/reperfusion

Hamida Saba, Ines Batinic-Haberle, Shankar Munusamy, Tanecia Mitchell, Cheryl Lichti, Judit Megyesi, Lee Ann MacMillan-Crow

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

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-PyP5+), using the rat renal I/R model. This was the first study to examine the effects of MnTnHex-2-PyP5+ 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 μg/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-β subunit as a key protein induced by MnTnHex-2-PyP5+ treatment alone and complex V (ATP synthase) as a target of injury during renal I/R. These results showed that MnTnHex-2-PyP5+ protected against renal I/R injury via induction of key mitochondrial proteins that may be capable of blunting oxidative injury.

Original languageEnglish (US)
Pages (from-to)1571-1578
Number of pages8
JournalFree Radical Biology and Medicine
Volume42
Issue number10
DOIs
StatePublished - May 15 2007
Externally publishedYes

Fingerprint

Porphyrins
Manganese
Superoxide Dismutase
Reperfusion
Ischemia
Adenosine Triphosphate
Kidney
Oxidative stress
Wounds and Injuries
Reperfusion Injury
Rats
Animals
Antioxidants
Tissue
Mitochondrial Proteins
Oxidative Stress
Animal Models
Oxidants
Surgery
Tissue and Organ Procurement

Keywords

  • Free radicals
  • Ischemia/reperfusion
  • Kidney
  • Metalloporphyrin
  • Mitochondria
  • MnSOD
  • Nitrotyrosine
  • Oxidants
  • Proteomics

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Saba, H., Batinic-Haberle, I., Munusamy, S., Mitchell, T., Lichti, C., Megyesi, J., & MacMillan-Crow, L. A. (2007). Manganese porphyrin reduces renal injury and mitochondrial damage during ischemia/reperfusion. Free Radical Biology and Medicine, 42(10), 1571-1578. https://doi.org/10.1016/j.freeradbiomed.2007.02.016

Manganese porphyrin reduces renal injury and mitochondrial damage during ischemia/reperfusion. / Saba, Hamida; Batinic-Haberle, Ines; Munusamy, Shankar; Mitchell, Tanecia; Lichti, Cheryl; Megyesi, Judit; MacMillan-Crow, Lee Ann.

In: Free Radical Biology and Medicine, Vol. 42, No. 10, 15.05.2007, p. 1571-1578.

Research output: Contribution to journalArticle

Saba, H, Batinic-Haberle, I, Munusamy, S, Mitchell, T, Lichti, C, Megyesi, J & MacMillan-Crow, LA 2007, 'Manganese porphyrin reduces renal injury and mitochondrial damage during ischemia/reperfusion', Free Radical Biology and Medicine, vol. 42, no. 10, pp. 1571-1578. https://doi.org/10.1016/j.freeradbiomed.2007.02.016
Saba, Hamida ; Batinic-Haberle, Ines ; Munusamy, Shankar ; Mitchell, Tanecia ; Lichti, Cheryl ; Megyesi, Judit ; MacMillan-Crow, Lee Ann. / Manganese porphyrin reduces renal injury and mitochondrial damage during ischemia/reperfusion. In: Free Radical Biology and Medicine. 2007 ; Vol. 42, No. 10. pp. 1571-1578.
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