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Tempol protects the gallbladder against ischemia/reperfusion

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Abstract

Impairment in gallbladder emptying, increase in residual volume, and reduced smooth muscle contractility are hallmarks of acute acalculous cholecystitis and seem to be related to ischemia/reperfusion (I/R). This study was designed to determine the effects of tempol, a general antioxidant, on I/R-induced changes in gallbladder contractile capacity, the mechanisms involved in the contractile process, and the level of inflammatory mediators. Experimental gallbladder I/R was induced in male guinea pigs by common bile duct ligation for 2 days, then a deligation of the duct was performed and after 2 days the animals were sacrificed. A group of animals was treated with tempol, administered in the drinking water at 1 mmol/l for 10 days prior the bile duct ligation and until animal sacrifice. Isometric tension recordings showed that KCl and cholecystokinin-induced contractions were impaired by I/R, which correlated with decreased F-actin content and detrimental effects on Ca2+ influx. In addition, I/R depolarized mitochondrial membrane potential, as indicated by the reduction of the heterogeneity of the rhodamine123 fluorescence signal, and increased the expression of NF-κB, COX-2, and iNOS. Tempol treatment improved contractility via normalization of Ca2+ handling and improvement of F-actin content. Moreover, the antioxidant ameliorated mitochondrial polarity and normalized the expression levels of the inflammatory mediators. These results show that antioxidant treatment protects the gallbladder from I/R, indicating the potential therapeutic benefits of tempol in I/R injury.

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Acknowledgments

The authors thank Purificación Delgado for technical assistance. This work was supported by Ministerio de Educacion y Ciencia (BFU 2007-60563), Junta de Extremadura (PRI07A069), FEDER and Instituto de Salud Carlos III (RETICEF: RD06/0013/1012 and RD06/0013/0002)

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Authors and Affiliations

  1. Department of Physiology, Nursing School, University of Extremadura, 10071, Caceres, Spain

    Pedro J. Gomez-Pinilla, Pedro J. Camello & María José Pozo

  2. Department of Physiology, Medicine School, University Complutense of Madrid, 28040, Madrid, Spain

    Jesus A. F. Tresguerres

  3. Department of Physiology, Nursing School, Avda Universidad s/n, 10003, Cáceres, Spain

    María José Pozo

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  1. Pedro J. Gomez-Pinilla
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  2. Pedro J. Camello
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  4. María José Pozo
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Correspondence to María José Pozo.

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Gomez-Pinilla, P.J., Camello, P.J., Tresguerres, J.A.F. et al. Tempol protects the gallbladder against ischemia/reperfusion. J Physiol Biochem 66, 161–172 (2010). https://doi.org/10.1007/s13105-010-0021-y

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