Nitric oxide protects the ultrastructure of pancreatic acinar cells in the course of caerulein‐induced acute pancreatitis

Abstract

Nitric oxide (NO) as a unique biological mediator that has been implicated in many physiological and pathophysiological processes may have a significant influence on the course of acute pancreatitis and the recovery process. The aim of the study was to evaluate the effect of a NO synthase inhibitor or a substrate for NO endogenous production on the ultrastructural features of the acinar cells in the course of caerulein-induced acute pancreatitis. Acute pancreatitis was induced in the rats by a supramaximal dose of caerulein. During acute pancreatitis induction, the rats were treated with L-arginine (the substrate for NO synthesis), NG-nitro-L-arginine (L-NNA, NO synthase inhibitor), L-arginine + L-NNA or saline. Light and electron microscopy examinations were performed in all groups after pancreatitis induction and additionally after 7 and 14 days of recovery. The study demonstrated that the NO synthase inhibitor given during pancreatitis induction in rats enhances the damage to the acinar cells, detected ultrastructurally, and increases the cellular inflammatory infiltration. In the later period, the considerable damage to the mitochondria and the changes in secretory compartment were observed, including dilated cisternae of Golgi apparatus, focal degranulation of rough endoplasmic reticulum, and reduced number of zymogen granules and condensing vacuoles. L-arginine reversed to some extent the deleterious effect of L-NNA, although when administered alone it had no apparent effect on the ultrastructure of pancreatic acinar cells compared with untreated animals. The obtained results indicate that the NO synthase inhibitor enhances the ultrastructural degenerative alterations in the pancreatic acinar cells in the course of caerulein-induced acute pancreatitis and confirm the protective role of endogenous nitric oxide in this disease.

The Beneficial Effects of Pentoxifylline on Caerulein-Induced Acute Pancreatitis in Rats

“…Caerulein is an agent used for hyperstimulation of AP in experimental models [4][5][6][7]. Caerulein is a decapeptide and the analog of cholecystokinin, which has a similar effect to cholecystokinin.…”

Nitric oxide regulates bacterial translocation in experimental acute edematous pancreatitis

“…In a previous model of caerulein-induced acute pancreatitis, Werner et al [14] found that L-NAME treatment increased the severity of inflammation, while decreasing pancreatic tissue oxygenation. In addition both Konturek et al [11] and Andrzejewska and Jurkowska [13] found that L-NNA significantly potentiated inflammatory changes in pancreas induced by caerulein injection.…”

“…Rats that received L-arginine alone, or in combination with the NO synthase inhibitor N(G)-nitro-L-arginine (L-NNA), experienced augmented cell proliferation after acute pancreatitis induction followed by earlier recovery compared with those with untreated acute pancreatitis or that only received L-NNA [12]. In another study, Andrzejewska and Jurkowska [13] demonstrated that while L-arginine treatment reverses some of the deleterious effects of L-NNA, it does not affect acinar cell ultrastructure.…”

Comparative Effects of Several Therapatic Agents on Hepatic Damage Induced by Acute Experimental Pancreatitis

“…Leukocytes and macrophages can initiate or aggravate cell damage through different mechanisms, including ROS, cytokines and a large quantity of nitric oxide produced by the inducible NOS [26,29,30]. NO has been found to be beneficial in protection of the ultrastructure of pancreatic acinar cell in AP [31]. We have determined beneficial effects of L-arginine on histopathological pancreatic damage and on increases in serum amylase and lipase levels during acute experimental pancreatitis (unpublished data).…”