Hydrogen sulfide preconditioning or neutrophil depletion attenuates ischemia-reperfusion-induced mitochondrial dysfunction in rat small intestine.

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.

• 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)

Chemical References

• Benzimidazoles
• Potassium Channels, Calcium-Activated
• Sulfides
• Tumor Necrosis Factor-alpha
• NS 1619
• Cytochromes c
• Peroxidase
• sodium bisulfide
• Hydrogen Sulfide

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)