The Role of Nitric Oxide in Experimental Cerulein Induced Pancreatitis

Abstract

An enhanced formation of nitric oxide (NO), due to the induction of inducible nitric oxide synthase (iNOS), has been implicated in the pathogenesis of shock and inflammation, but its role in acute pancreatitis still remains controversial. To clarify the role of NO in acute pancreatitis, the present experiment investigated the expression of iNOS and the effect of NOS inhibition on cerulein-induced pancreatitis in rats. Group I received intraperitoneal (ip) injection of normal saline. Group II received two ip injections of cerulein (20 g/kg). Group III received injections of N G -nitro-L-arginine methyl ester (L-NAME) (30 mg/kg) with cerulein. Group IV received Larginine (250 mg/kg) with cerulein and L-NAME. The expression of iNOS in the pancreas was examined by western blot analysis. The plasma concentration of NO metabolites was measured. The severity of pancreatitis was assessed by measuring serum amylase, pancreas water content and histopathological examination. Compared with controls, the cerulein group displayed significantly increased expression of iNOS and raised plasma NO metabolites. Treatment with L-NAME significantly decreased hyperamylasemia, plasma NO level, and the extent of pancreatic injury. Treatment with L-arginine reversed the effects of L-NAME. These findings suggest that an enhanced formation of NO by iNOS plays an important role in the development of acute pancreatitis, and inhibition of NO production has the beneficial effects in reducing pancreas injury.

Influence of dexamethasone on mesenteric lymph node of rats with severe acute pancreatitis

“…As one of the important common mediators in inflammatory mediator cascade reaction of inflammatory reaction [15][16][17] , Nitric oxide (NO) can be regarded as an index of SAP. However, some researchers [18] believe that a small amount of endogenous NO can protect the body from ischemiareperfusion injury, and prevent any increase in intestinal vasopermeability induced by endotoxemia and bacteria translocation.…”

Free radicals and the pancreatic acinar cells: role in physiology and pathology

“…NO overproduction by iNOS in the pancreas is implicated in the exacerbation of cell injury during AP (Lomis et al 1995;Viola et al 2000;Ayub et al 2001;Simsek et al 2001;Cuzzocrea et al 2002;Ozturk et al 2003;Um et al 2003;Chen et al 2004;Isik et al 2004;Sandstrom et al 2005). One possible mechanism of NO-mediated damage is potentiation of oxidative stress by NO.…”

Acute Pancreatitis Affects Non-Parenchymal Liver Cells by a Mechanism Dependent on Platelet-Activating Factor

“…It has been demonstrated that an enhanced formation of NO plays an important role in the pathogenesis of experimental acute pancreatitis, since NO synthase inhibition decreases the severity of pancreatitis [12,13] . In addition, excess of NO is an important factor underlying the systemic haemodynamic disturbance and oxidative tissue damage associated with acute pancreatitis [14] .…”