Specific inhibition of mitochondrial oxidative stress suppresses inflammation and improves cardiac function in a rat pneumonia-related sepsis model

Qun S. Zang, Hesham Sadek, David L. Maass, Bobbie Martinez, Lisha Ma, Jessica A. Kilgore, Noelle S. Williams, Doug E. Frantz, Jane G. Wigginton, Fiemu E. Nwariaku, Steven Wolf, Joseph P. Minei

Research output: Contribution to journalArticle

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Abstract

Using a mitochondria-targeted vitamin E (Mito-Vit-E) in a rat pneumonia-related sepsis model, we examined the role of mitochondrial reactive oxygen species in sepsismediated myocardial inflammation and subsequent cardiac contractile dysfunction. Sepsis was produced in adult male Sprague-Dawley rats via intratracheal injection of S. pneumonia (4 × 10 6 colony formation units per rat). A single dose of Mito-Vit-E, vitamin E, or control vehicle, at 21.5 μmol/kg, was administered 30 min postinoculation. Blood was collected, and heart tissue was harvested at various time points. Mito-Vit-E in vivo distribution was confirmed by mass spectrometry. In cardiac mitochondria, Mito-Vit-E improved total antioxidant capacity and suppressed H 2O 2 generation, whereas vitamin E offered little effect. In cytosol, both antioxidants decreased H 2O 2 levels, but only vitamin E strengthened antioxidant capacity. Mito- Vit-E protected mitochondrial structure and function in the heart during sepsis, demonstrated by reduction in lipid and protein oxidation, preservation of mitochondrial membrane integrity, and recovery of respiratory function. While both Mito-Vit-E and vitamin E suppressed sepsis-induced peripheral and myocardial production of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), Mito-Vit-E exhibited significantly higher efficacy (P < 0.05). Stronger anti-inflammatory action of Mito-Vit-E was further shown by its near-complete inhibition of sepsis-induced myeloperoxidase accumulation in myocardium, suggesting its effect on neutrophil infiltration. Echocardiography analysis indicated that Mito-Vit-E ameliorated cardiac contractility of sepsis animals, shown by improved fractional shortening and ejection fraction. Together, our data suggest that targeted scavenging of mitochondrial reactive oxygen species protects mitochondrial function, attenuates tissue-level inflammation, and improves whole organ activities in the heart during sepsis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume302
Issue number9
DOIs
StatePublished - May 1 2012
Externally publishedYes

Fingerprint

Vitamin E
Sepsis
Pneumonia
Oxidative Stress
Mitochondria
Inflammation
Tocopherols
Antioxidants
Reactive Oxygen Species
Neutrophil Infiltration
Recovery of Function
Mitochondrial Membranes
Interleukin-1
Cytosol
Peroxidase
Sprague Dawley Rats
Echocardiography
Interleukin-6
Mass Spectrometry
Myocardium

Keywords

  • Heart failure
  • Mitochondria-targeted antioxidants
  • Mitochondrial damage
  • Myocardial inflammation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Specific inhibition of mitochondrial oxidative stress suppresses inflammation and improves cardiac function in a rat pneumonia-related sepsis model. / Zang, Qun S.; Sadek, Hesham; Maass, David L.; Martinez, Bobbie; Ma, Lisha; Kilgore, Jessica A.; Williams, Noelle S.; Frantz, Doug E.; Wigginton, Jane G.; Nwariaku, Fiemu E.; Wolf, Steven; Minei, Joseph P.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 302, No. 9, 01.05.2012.

Research output: Contribution to journalArticle

Zang, Qun S. ; Sadek, Hesham ; Maass, David L. ; Martinez, Bobbie ; Ma, Lisha ; Kilgore, Jessica A. ; Williams, Noelle S. ; Frantz, Doug E. ; Wigginton, Jane G. ; Nwariaku, Fiemu E. ; Wolf, Steven ; Minei, Joseph P. / Specific inhibition of mitochondrial oxidative stress suppresses inflammation and improves cardiac function in a rat pneumonia-related sepsis model. In: American Journal of Physiology - Heart and Circulatory Physiology. 2012 ; Vol. 302, No. 9.
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AU - Ma, Lisha

AU - Kilgore, Jessica A.

AU - Williams, Noelle S.

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