Tempol, a Membrane-Permeable Radical Scavenger, Exhibits Anti-Inflammatory and Cardioprotective Effects in the Cerulein-Induced Pancreatitis Rat Model

Abstract

To date, it remains unclear whether mild form of acute pancreatitis (AP) may cause myocardial damage which may be asymptomatic for a long time. Pathogenesis of AP-related cardiac injury may be attributed in part to ROS/RNS overproduction. The aim of the present study was to evaluate the oxidative stress changes in both the pancreas and the heart and to estimate the protective effects of 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (tempol) at the early phase of AP. Cerulein-induced AP led to the development of acute edematous pancreatitis with a significant decrease in the level of sulfhydryl (-SH) groups (oxidation marker) both in heart and in pancreatic tissues as well as a substantial increase in plasma creatine kinase isoenzyme (CK-MB) activity (marker of the heart muscle lesion) which confirmed the role of oxidative stress in the pathogenesis of cardiac damage. The tempol treatment significantly reduced the intensity of inflammation and oxidative damage and decreased the morphological evidence of pancreas injury at early AP stages. Moreover, it markedly attenuated AP-induced cardiac damage revealed by normalization of the -SH group levels and CK-MB activity. On the basis of these studies, it is possible to conclude that tempol has a profound protective effect against cardiac and pancreatic damage induced by AP.

Figure 1

Effect of cerulein (15 μg/kg/h for 4 h) given alone or in combination with tempol on serum amylase activity and pancreatic water content. Mean ± SEM. ^∗ p < 0.05 compared with control. ^# p < 0.05 compared with cerulein given alone.

Figure 2

Histologic section of pancreas: (a) control rats—normal pancreatic structures were observed, (b) the rats subjected to cerulein-induced pancreatitis (AP) alone—evidences of edema, vacuolization, inflammatory cell infiltrate, and necrosis were noted, (c, d) the AP animals treated with tempol—note the significant reduction in edema, vacuolization, and inflammation, without any evidence of necrosis as compared to untreated animals (b). H&E staining; original magnification, ×20.

Figure 3

Effect of administration of tempol on oxidative stress parameters in pancreatic homogenates of rats with cerulein-induced pancreatitis. Mean ± SEM. ^∗ p < 0.05 compared with control.

Figure 4

Effect of administration of tempol on oxidative stress parameters in heart homogenates of rats with cerulein-induced pancreatitis. Mean ± SEM. ^∗ p < 0.05 compared with control. ^# p < 0.05 compared with cerulein given alone.

Figure 5

Effect of administration of tempol on plasma total antioxidant capacities measured by FRAP of rats with cerulein-induced pancreatitis. Mean ± SEM. ^∗ p < 0.05 compared with control. ^# p < 0.05 compared with cerulein given alone.

Figure 6

Effect of administration of tempol on activity of serum creatine kinase MB (CK-MB) of rats with cerulein-induced pancreatitis. Mean ± SEM. ^∗ p < 0.05 compared with control. ^# p < 0.05 compared with cerulein given alone.