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.