Methods: A total of 35 female Sprague-Dawley rats were randomly divided into five groups (n=7). Median laparotomy and a 45-min bilateral kidney ischemia were performed. Oral medications were administered three days before the surgical intervention (20 mg/kg cilostazol, 10 mg/kg rosuvastatin and 20 mg/kg cilostazol + 10 mg/kg rosuvastatin). Blood samples and kidney and heart tissue samples were extracted one day after surgery.

Results: Immunohistochemical examination of the kidney samples revealed that tumor necrosis factor-alpha and hypoxia-inducible factor-1 alpha immunoreactivities in the cilostazol, rosuvastatin, and cilostazol + rosuvastatin groups were found to be significantly lower, compared to ischemia/reperfusion injury group (p<0.05). Immunohistochemical examination of the heart samples revealed that tumor necrosis factor-alpha immunoreactivity was significantly lower in the cilostazol group, compared to ischemia/reperfusion injury group. Hypoxia-inducible factor-1 alpha immunoreactivities were significantly lower in the cilostazol, rosuvastatin, and cilostazol + rosuvastatin groups, compared to ischemia/reperfusion injury group (p<0.05). Serum urea, creatinine, creatine kinasemuscle and brain, and troponin levels were significantly lower in the cilostazol, rosuvastatin, and cilostazol + rosuvastatin groups, compared to ischemia/reperfusion injury group (p<0.05).

Conclusion: Cilostazol and rosuvastatin have protective effects on kidney ischemia/reperfusion and remote cardiac reperfusion injury, and the protective effect can be augmented with cilostazol monotherapy, compared to combined therapy.