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ANESTHETIC PHARMACOLOGY

The Role of K_ATP Channels on Propofol Preconditioning in a Cellular Model of Renal Ischemia-Reperfusion

Alexandra R. Assad, MD, PhD^*, João Marcos A. Delou, MS, Leonardo M. Fonseca, MS, Nivaldo R. Villela, PhD^*, José Hamilton M. Nascimento, PhD, Nubia Verçosa, PhD^*, Anibal Gil Lopes, PhD, and Márcia A.M. Capella, PhD

From the *Programa de Pós-Graduação em Cirurgia Geral—Setor de Anestesiologia, Hospital Universitario Clementino Fraga Filho, and Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Address correspondence and reprint requests to Márcia A. M. Capella, PhD, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS-Bloco G, 21949-900, Rio de Janeiro, RJ, Brazil. Address e-mail to mcapella{at}biof.ufrj.br.

BACKGROUND: Propofol (2,6-diisopropylphenol) has been shown to protect several organs, including the kidneys, from ischemia-reperfusion (I-R)-induced injury. Although propofol affects adenosine triphosphate-sensitive potassium (K_ATP) channels in nonrenal tissues, it is still not clear by which mechanisms propofol protects renal cells from such damage. In this study, we investigated whether propofol induces renal preconditioning through renal K_ATP channels.

METHODS: A reversible ATP depletion (antimycin A) followed by restoration of substrate supply in LLC-PK1 cells was used as an in vitro model of renal I-R. Cell viability was assessed by dimethylthiazol-diphenyltetrazol bromide and trypan blue dye exclusion test assays. Apoptosis was evaluated by annexin V–fluorescein isothiocyanate staining by flow cytometry and immunofluorescence. Propofol treatments were initiated at various time intervals: 1 or 24 h before ischemia, only during ischemia, or only during reperfusion. To evaluate the mechanisms of propofol protection, specific K_ATP channel inhibitors or activators were used in some experiments during propofol pretreatment.

RESULTS: Propofol attenuated I-R injury on LLC-PK1 cells when present either 1 or 24 h before initiated I-R, and also during the recovery period, but not when added only during ischemia. Propofol pretreatment significantly protected LLC-PK1 from I-R-induced apoptosis. The protective effect of propofol was prevented by glibenclamide (a sarcolemmal ATP-dependent K⁺ channel blocker) and decreased by 5-hydroxidecanoic acid (a mitochondrial ATP-dependent K⁺ channel blocker), but it was not modified by diazoxide (a selective opener of ATP-sensitive K⁺ channel).

CONCLUSION: Propofol protected cells against apoptosis induced by I-R. This protection was probably due to a preconditioning effect of propofol and was, at least in part, mediated by K_ATP channels.