Tempol protects the gallbladder against ischemia/reperfusion

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 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.

TEMPOL has limited protective effects on renal oxygenation and hemodynamics but reduces kidney damage and inflammation in a rat model of renal ischemia/reperfusion by aortic clamping

“…TEMPOL has been shown to reduce post-ischemic inflammatory signaling in a rat [54] and mouse [57] model of renal I/R and a Guinea pig model of gallbladder I/R [56]. Oxidative stress and cell death during I/R lead to highly pleiotropic immune signaling and sterile inflammation [9], which was confirmed in our model on the basis of the IL-6 ( Figure 3B) and MPO data ( Figure 3G, H).…”

“…Accordingly, numerous studies have shown that TEMPOL reduces I/R AKI in different species, including rats [54]. The antioxidant [55], immunosuppressive [56,57], and AKIameliorating effects of TEMPOL are well-established in I/R AKI. Conversely, relatively little information is available in terms of renal oxygenation, which is critical for renal function [8].…”

Enhanced Expression of Cystathionine β-Synthase and Cystathionine γ-Lyase During Acute Cholecystitis-Induced Gallbladder Inflammation

“…Acute acalculous cholecystitis (AC) is characterized by gallbladder inflammation without evidence of calculi or sludge [1]. Bile stasis, ischemia-reperfusion injury, and systemic inflammatory response syndrome (SIRS) have been suggested as pathogenic factors [2].…”

“…Bile stasis, ischemia-reperfusion injury, and systemic inflammatory response syndrome (SIRS) have been suggested as pathogenic factors [2]. In critically ill patients, AC is believed to have a more fulminant course, and is associated with significantly higher morbidity and mortality than gallstone-associated acute cholecystitis [1]. Common bile duct ligation (CBDL) in the guinea pig produces a histologic picture that is nearly identical to that of acute human cholecystitis, with subserosal edema, hemorrhage, white blood cell infiltration, and vasodilation [3].…”

Acute Acalculous Cholecystitis following The Cemented Hemiarthroplasty in an Elderly Hip Fracture Patient: Case Report

“…Postoperative AAC was unrelated to the biliary tract, which was characterized by gallbladder inflammation without evidence of calculi or sludge [8]. …”