Tempol protects the gallbladder against ischemia/reperfusion.
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 Ca(2+) 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-kappaB, COX-2, and iNOS. Tempol treatment improved contractility via normalization of Ca(2+) 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.
Gomez-Pinilla
Pedro J
PJ
Department of Physiology, Nursing School, University of Extremadura, 10071 Caceres, Spain.
Camello
Pedro J
PJ
Tresguerres
Jesus A F
JA
Pozo
María José
MJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003135:Common Bile Duct / Q000601:surgery; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D005704:Gallbladder / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D016473:Gallbladder Emptying / Q000187:drug effects; D006168:Guinea Pigs; D008026:Ligation; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D015427:Reperfusion Injury / Q000517:prevention & control*; D013113:Spin Labels
D003497:Cyclic N-Oxides; D013113:Spin Labels; D002118:Calcium; C001803:tempol