title: 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.affiliation: Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri 65212, USA.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Liu
authors.forename: Theodore
authors.initials: T
authors.lastname: Kalogeris
authors.forename: Meifang
authors.initials: M
authors.lastname: Wang
authors.forename: Mozow Yusof
authors.initials: MY
authors.lastname: Zuidema
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Dai
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davis
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hill
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Korthuis
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage; D045304:Cytochromes c / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism; D007410:Intestinal Diseases / Q000209:etiology / Q000517:prevention & control*; D007421:Intestine, Small / Q000098:blood supply*; D019194:Ischemic Preconditioning / Q000379:methods*; D047589:Leukocyte Reduction Procedures; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D028361:Mitochondrial Diseases / Q000209:etiology / Q000517:prevention & control*; D009504:Neutrophils; D009195:Peroxidase / Q000032:analysis; D024681:Potassium Channels, Calcium-Activated / Q000819:agonists / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*; D013440:Sulfides / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D001562:Benzimidazoles; D024681:Potassium Channels, Calcium-Activated; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; C086491:NS 1619; D045304:Cytochromes c; D009195:Peroxidase; C025451:sodium bisulfide; D006862:Hydrogen Sulfide