Different effects of dexamethasone and the nitric oxide synthase inhibitor L-NAME on caerulein-induced rat acute pancreatitis, depending on the severity

Abstract

Effects of dexamethasone and N(G)-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on caerulein-induced acute pancreatitis were examined in rats. Acute pancreatitis was induced by caerulein (20 mug/kg, s.c.) given repeatedly 2 or 4 times every hour, and serum amylase levels, pancreas weight and myeloperoxidase (MPO) activity were measured 6 h after the first injection of caerulein. Dexamethasone (3 mg/kg) and L-NAME (30 mg/kg) were administered p.o. 30 min before the first injection of caerulein. Caerulein caused moderate or severe pancreatitis, depending on the times of injections, resulting in different degrees of increase in serum amylase levels and pancreas weight, and the marked elevation of MPO activity was observed only after injections of caerulein given 4 times per hour. Both dexamethasone and L-NAME suppressed the severity of pancreatits, yet the effect of L-NAME as compared with dexamethasone was more potent against mild pancreatitis but less potent against severe pancreatitis. These results suggest that caerulein-induced acute pancreatitis shows different responsiveness to L-NAME and dexamethasone, depending on the severity; the former is more effective against pancreatitis with less inflammation, while the latter is more effective against pancreatitis with severe inflammation. It is assumed that endogenous NO may be involved in oedema formation as the early event in the development of acute pancreatitis.

Effects of large dose of dexamethasone on inflammatory mediators and pancreatic cell apoptosis of rats with severe acute pancreatitis

“…In 1952, Stephensen et al [21] for the first time reported the effect of glucocorticoid in AP treatment. Many empirical studies show glucocorticoid can improve the survival of AP animals [22,23] Its mechanisms mainly are: inhibiting the generation of inflammatory mediators and (or) inhibiting the effects of inflammator y mediators, enhancing body stress, improving microcirculation, alleviating endotoxemia, cleaning free radicals, inhibiting nitric oxide (NO) and expression of NF-κB, etc [22,24,25] . In terms of administration and dose, Dong et al [26,27] found a large dose of dexamethasone was obviously superior to the small dose dexamethasone in therapeutic effect and early use of dexamethasone was superior to dexamethasone of the same dose 5 h later.…”

Effects of dexamethasone and Salvia miltiorrhiza on multiple organs in rats with severe acute pancreatitis

“…Since it can inhibit the inflammatory response in many diseases, dexamethasone is widely used in the treatment of severe infections (Zhang X.P., et al, 2006;Zhang X., et al, 2008). Moreover, it can inhibit the expression of multiple inflammatory mediator genes and antagonize the effects of inflammatory mediators by increasing the synthesis of anti-inflammatory proteins, thereby producing therapeutic effects on SAP rats (Sugiyama et al, 2005;Kandil et al, 2006;Muller et al, 2008).…”

Study of dexamethasone, baicalin and octreotide on brain injury of rats with severe acute pancreatitis

“…Current studies confirmed glucocorticoid represented by DXM mainly acts on AP/SAP in the following ways: inhibit the production and/or action of inflammatory mediators, increase physical stress, improve microcirculation, alleviate endotoxemia, eliminate free radicals, inhibit NF-jB and so on [40][41][42]. Sugiyama et al used DXM (3 mg/kg) and L-NAME (30 mg/kg) to treat AP rats, and found that both DXM and L-NAME can suppress the severity of AP, yet the effect of L-NAME as compared with DXM was more potent against mild pancreatitis but less potent against severe pancreatitis.…”