Cilostazol induces angiogenesis and regulates oxidative stress in a dose-dependent manner: A chorioallantoic membrane study

Abstract

ABSTRACT Background: In this study, we aimed to investigate the effects of cilostazol on angiogenesis and oxidative stress using the chorioallantoic membrane model. Methods: In this experimental study, the Ross 308 chick embryos were used. The negative control group (n=10) received no intervention. The positive control group (n=10) consisted of eggs treated with epidermal growth factor for inducing angiogenesis. Three cilostazol groups were designed with 10-7 (n=10), 10-6 (n=10), and 10-5 (n=10) M concentrations. Each egg was punctured on the sixth day of incubation, and drug pellets were introduced to the positive control and drug groups at the prespecified doses. Vascular development was evaluated on the eighth day of application. The total oxidant status, total antioxidant capacity, and oxidative stress index levels were determined from albumen liquids obtained with a syringe before and after drug application. Results: Lower oxidative stress index levels were obtained from the positive control and cilostazol groups compared to the negative control albumens (p=0.001). The increments in vascular junctions and newly developed vascular nodules were evaluated in drug-free and drug-applied chorioallantoic membranes. The highest activity was obtained in the 10-7 M concentration cilostazol group. An increased angiogenic activity was detected in all drug groups in each concentration compared to the negative control group (p=0.001). Angiogenic activity was similar in all the cilostazol-treated groups (p=0.43). Conclusion: Cilostazol has a positive stimulant effect on angiogenesis and it seems to suppress oxidative stress during embryonic growth. Cilostazol exerts these effects significantly and similarly at different doses