Attenuation of Gastric Mucosal Inflammation Induced by Aspirin Through Inhibition of Selective Type III Phospshodiesterase in Rats

Abstract

Cilostazol, a selective type III phosphodiesterase inhibitor, is widely used for treatment of ischemic symptoms of peripheral vascular disease. Recent studies have reported that the mechanism of cilostazol is related to suppression of pro-inflammatory cytokine production and improvement of local microcirculation disturbances. The activation of inflammatory cells and pro-inflammatory cytokine production play critical roles in the pathogenesis of aspirin-induced gastric irritation. The aim of the present study was to determine whether cilostazol can ameliorate aspirin-induced gastric mucosal lesions in rats, reduce neutrophil accumulation, and reduce the production of pro-inflammatory cytokines. Gastric lesions were produced by oral gavage of aspirin (200 mg/kg) and HCl (0.15 N, 8.0 ml/kg). Cilostazol (1-10 mg/kg, IP) was injected 30 min before aspirin administration. Also, we measured the gastric mucosal concentrations of myeloperoxidase and interleukin-1 beta, tumor necrosis factor-alpha, and cytokine-induced neutrophil chemoattractants-1, as an index of neutrophil accumulation, and the pro-inflammatory cytokines. Cilostazol ameliorated the gastric mucosal lesions induced by aspirin administration (P<0.01). The gastric contents of myeloperoxidase and pro-inflammatory cytokines were all increased after aspirin administration and significantly reduced by cilostazol treatment. In this study, we demonstrated that a selective type III phosphodiesterase inhibitor, cilostazol, reduced aspirin-induced gastric inflammation and damage via suppression of the production of proinflammatory cytokines. Cilostazol may be useful for preventing gastric mucosal lesions induced by aspirin.

Effect of probiotics on aspirin-induced gastric mucosal lesions

“…We determined that aspirin administration caused proinflammatory cytokine response in the stomach; however, differences between the rat groups were not statistically significant, while previous studies showed a significant increase in proinflammatory cytokines (30,31). In these studies, acidified aspirin was used to provide more evident inflammatory response, including TNF-α and IL-1 beta (5,30,31).…”

“…In these studies, acidified aspirin was used to provide more evident inflammatory response, including TNF-α and IL-1 beta (5,30,31). In our model, we also think that peaked levels of TNF-α and IL-2 could precede the sampling time.…”

Pharmacodynamic Effects of Cilostazol Versus Clopidogrel in Stented Patients under Proton Pump Inhibitor Co-administration: The ACCEL-PARAZOL Study

“…A recent randomized, crossover study of healthy CYP2C19 ＊ 1/ ＊ 1 subjects (n = 160) also demonstrated that the effect of omeprazole on the plasma concentration and antiplatelet actions of clopidogrel appears to be greater than that of lansoprazole 6) . The results of the present study including stented patients highlight the significant interaction between lansoprazole and clopidogrel, although the observed stress-induced gastric mucosal inflammation and injury by suppressing the production of pro-inflammatory cytokines in rats 35,36) . In contrast to aspirin and thienopyridine, cilostazol does not significantly prolong the bleeding time; this property remains even when cilostazol is added to other antiplatelet regimens 37) .…”

“…On the other hand, clopidogrel does not have a direct effect on the gastric mucosa, but rather inhibits the healing process of gastric mucosal injury induced by aspirin. In contrast to that observed with aspirin and clopidogrel, several experimental studies have shown the beneficial effects of cilostazol on gastric mucosal damage and/or bleeding [34][35][36][37] . Compared with aspirin, cilostazol significantly ameliorated microcirculatory and villous damage to the intestinal mucosa following ischemia-reperfusion injury in a mice study 34) .…”

Gastroduodenal toxicity of low-dose acetylsalicylic acid: a comparison with non-steroidal anti-inflammatory drugs

“…Abnormalities in microcirculation ASA causes alterations in the local microcirculation 97 , as demonstrated in a recent study of cilostazol, a selective type III phosphodiesterase inhibitor that was shown to ameliorate ASA-induced gastric mucosal lesions 98 . Additionally, neutrophil infiltration was inhibited, providing further evidence for a role of neutrophil-mediated inflammation in ASA-induced gastroduodenal injury 98 .…”