Inflammopharmacology 14 (2006) 169–175 0925-4692/06/040169–7 DOI 10.1007/s10787-006-1524-■■■ © Birkhäuser Verlag, Basel, 2006 Inflammopharmacology Research Article Protective effects of nedocromil sodium and sodium cromo- glycate on gastroduodenal ulcers: a comparative study in rats Mohammad Tariq 1,* , Meshal Al Moutaery 1 , Ibrahim Elfaki 1 , Mohammad Arshaduddin 1 , Haseeb Ahmad Khan 2 1 Research Center, Armed Forces Hospital, P.O. Box 7897 (W-912), Riyadh 11159, Saudi Arabia, e-mail: rkh_research@yahoo.com 2 Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia Received 29 April 2006; revised: 26 May 2006; accepted: 26 May 2006 Abstract. Stabilization of mast cells plays a key mechanism to protect gastrointestinal tract from injury. This study presents a comparative evaluation of mast cell stabilizers nedocromil sodium (NDS) and sodium cromoglycate (SCG) in experimental gastric and duodenal ulcers in rats. Wistar rats of either sex were used in this study. Both NDS and SCG, in the doses of 10, 30 and 100 mg/kg were given intra- peritoneally for gastric secretion studies and by gavage for antiulcer studies. Acid secretion studies were undertaken in pylorus-ligated rats. Gastric lesions were induced by water immersion restraint stress (WIRS), indomethacin and etha- nol whereas duodenal ulcers were produced by cysteamine. The level of glutathione (GSH) and gastric wall mucus were measured in glandular stomach of rats following ethanol-in- duced gastric lesions. SCG was more effective than NDS in preventing WIRS- and indomethacin-induced gastric lesions whereas reverse was true in ethanol- and cysteamine-induced ulcers. All the 3 doses of SCG offered almost equal protection against WIRS-induced gastric lesions whereas only medium and high dose of NDS provided significant protection in this model of ulcer. NDS significantly inhibited cysteamine-induced duodenal ulcers whereas SCG failed to do so. Pretreatment with NDS or SCG significantly and dose-dependently protected gastric mucosa against ethanol-induced injury, while the former drug appeared to be more effective. The cytoprotective effects of these two drugs were accompanied by the attenuation of ethanol-induced depletion of gastric wall mucus and GSH. The differential ef- fects of NDS and SCG against various gastric lesions rational- ize the possible benefits of a combined therapy (NDS+SCG) for the treatment of complex gastroduodenal ulcers. Key words: Gastric ulcers; Duodenal ulcers; Mast cells; Nedocromil; Cromoglycate Introduction The acidity and volume of gastric acid secretion play a vital role in the pathogenesis of gastroduodenal ulcers (Nishida et al., 1994). Gastric acid secretion is precisely regulated by endo- crine, paracrine and neurocrine signals via gastrin-histamine and cholecystokinin-somatostatin pathways. Targeting these mediators by pharmacological agents has been shown to modi- fy the healing of gastric ulcers (Brimblecombe et al., 1975; Pendley et al., 1992; Tariq et al., 1987; Hung, 1998; Yamamoto et al., 2001). Besides hyperacidity, which is considered as one of the major aggressive factors for mucosal damage, body’s immune system response to ulcerogenic stimuli plays a critical role in the pathogenesis of gastric ulcers. Immunoactivation as a result of noxious stimuli is accompanied by a cascade of proinflammatory cytokines, neutrophil proteases and oxygen- derived free radicals (ODFR), which could be more injurious to host tissue than the primary ulcerogenic stimuli itself (Huang et al., 2001; Watanabe et al., 2000). On the other hand, immuno- neutralization or depletion of neutrophils has been shown to promote gastric ulcer healing (Huang et al., 2001; Watanabe et al., 2000; Shimizu et al., 2000). Gastrointestinal mast cells are one of the main proinflam- matory cells which are involved in undesirable pathologic effects such as food hypersensitivity, besides providing a natural defense against parasitic and microbial infections. Recently, mast cells have been implicated in the pathogene- sis of Helicobacter pylori-infected gastritis (Nakajima et al., 2004) whereas stabilization of mast cells has been suggested to be a key mechanism to protect the gastrointestinal tract from injury (Penissi et al., 2003). Involvement of mast cells in gastropathy is supported by the findings of animal studies showing the induction of gastric mucosal lesions by mast cell degranulators (Ohta et al., 2003; Kawakubo et al., 2005; Tabuchi et al., 1994) and their protection by mast cell stabi- lizers (Tabuchi et al., 1994; Ali, 1995; Erkasap et al., 2005; Takeuchi et al., 1986). * Corresponding author