Abstract |
The objectives of this study were to determine whether neutrophil depletion with anti-neutrophil serum (ANS) or preconditioning with the hydrogen sulfide (H(2)S) donor NaHS ( NaHS-PC) 24 h prior to ischemia-reperfusion (I/R) would prevent postischemic mitochondrial dysfunction in rat intestinal mucosa and, if so, whether calcium-activated, large conductance potassium (BK(Ca)) channels were involved in this protective effect. I/R was induced by 45-min occlusion of the superior mesenteric artery followed by 60-min reperfusion in rats preconditioned with NaHS ( NaHS-PC) or a BK(Ca) channel activator (NS-1619-PC) 24 h earlier or treated with ANS. Mitochondrial function was assessed by measuring mitochondrial membrane potential, mitochondrial dehydrogenase function, and cytochrome c release. Mucosal myeloperoxidase (MPO) and TNF-α levels were also determined, as measures of postischemic inflammation. BK(Ca) expression in intestinal mucosa was detected by immunohistochemistry and Western blotting. I/R induced mitochondrial dysfunction and increased tissue MPO and TNF-α levels. Although mitochondrial dysfunction was attenuated by NaHS-PC or NS-1619-PC, the postischemic increases in mucosal MPO and TNF-α levels were not. The protective effect of NaHS-PC or NS-1619-PC on postischemic mitochondrial function was abolished by coincident treatment with BK(Ca) channel inhibitors. ANS prevented the I/R-induced increase in tissue MPO levels and reversed mitochondrial dysfunction. These data indicate that neutrophils play an essential role in I/R-induced mucosal mitochondrial dysfunction. In addition, NaHS-PC prevents postischemic mitochondrial dysfunction (but not inflammation) by a BK(Ca) channel-dependent mechanism.
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Authors | Yajun Liu, Theodore Kalogeris, Meifang Wang, Mozow Yusof Zuidema, Qun Wang, Hongyan Dai, Michael J Davis, Michael A Hill, Ronald J Korthuis |
Journal | American journal of physiology. Gastrointestinal and liver physiology
(Am J Physiol Gastrointest Liver Physiol)
Vol. 302
Issue 1
Pg. G44-54
(Jan 01 2012)
ISSN: 1522-1547 [Electronic] United States |
PMID | 21921289
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Benzimidazoles
- Potassium Channels, Calcium-Activated
- Sulfides
- Tumor Necrosis Factor-alpha
- NS 1619
- Cytochromes c
- Peroxidase
- sodium bisulfide
- Hydrogen Sulfide
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Topics |
- Animals
- Benzimidazoles
(administration & dosage)
- Cytochromes c
(metabolism)
- Hydrogen Sulfide
(metabolism)
- Intestinal Diseases
(etiology, prevention & control)
- Intestine, Small
(blood supply)
- Ischemic Preconditioning
(methods)
- Leukocyte Reduction Procedures
- Male
- Membrane Potential, Mitochondrial
(drug effects)
- Mitochondria
(drug effects, enzymology)
- Mitochondrial Diseases
(etiology, prevention & control)
- Neutrophils
- Peroxidase
(analysis)
- Potassium Channels, Calcium-Activated
(agonists, antagonists & inhibitors)
- Rats
- Rats, Sprague-Dawley
- Reperfusion Injury
(complications)
- Sulfides
(administration & dosage)
- Tumor Necrosis Factor-alpha
(analysis)
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