Search

Background: Neutrophil migration, one of the major factors predisposing to nonsteroidal anti-inflammatory drugs (NSAIDs)-induced intestinal lesions, consists of several steps, including interaction with P-selectin from platelets. Cilostazol, a specific phosphodiesterase (PDE)-3 inhibitor, suppresses the expression of P-selectin from platelets and reduces interaction between platelets and leukocytes, leading to inflammatory amelioration in several disease models. We tried to clarify the therapeutic effectiveness of cilostazol for NSAID-induced small intestinal lesions., Subjects and Methods: 1) Anti-PSGL-1 antibody (2 mg/kg) or cilostazol (100 mg/kg) was administered to mice one hour before Indomethacin (IND, 2.5 mg/kg) administration for 4 days to evaluate small intestinal lesions. 2) IND-induced migratory behaviors of neutrophils and platelets were evaluated in intestinal vessels by an intravital microscopy., Results: i) IND induced small intestinal lesions with an increase in MPO activity. Anti-PSGL-1 antibody and cilostazol ameliorated intestinal lesions along with suppression of MPO activity. ii) Intravital microscopy revealed that administration of IND increased migration of platelet-bearing neutrophils. Cilostazol treatment ameliorated neutrophil migration by blocking interaction between platelets and neutrophils., Conclusion: Our results suggest that enhanced platelets-bearing neutrophil migration is critically involved in the pathogenesis of IND-induced small intestinal lesions and suggest a potential application of cilostazol for prevention of NSAID-induced small intestinal lesions.

The present study was undertaken to determine whether resveratrol (RVT) could ameliorate ionizing radiation-induced oxidative injury. After a 10-days pre-treatment with RVT (10 mg/kg/day p.o.), rats were exposed to whole-body IR (800 cGy) and the RVT treatment was continued for 10 more days after the irradiation. Irradiation caused a significant decrease in glutathione level, while malondialdehyde levels, myeloperoxidase activity and collagen content were increased in the liver and ileum tissues. Similarly, plasma lactate dehydrogenase and pro-inflammatory cytokine levels, 8-hydroxy-2'-deoxyguanosine and leukocyte apoptosis were elevated, while antioxidant-capacity was reduced in the irradiated rats as compared with the control group. Furthermore, Na(+), K(+)-ATPase activity was inhibited and DNA fragmentation was increased in the ileal tissues. Resveratrol treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. In conclusion, supplementing cancer patients with adjuvant therapy of resveratrol may have some benefit for a more successful radiotherapy.