The role of nicardipine in preventing ischemia/reperfusion damage in rats exposed to acute extremity ischemia

Objective: Limb ischemia, which is as common in our country as in the whole world, is one of the important causes of mortality and morbidity. It is known that most of the damage during ischemia and reperfusion process occurs during the reperfusion process and reactive oxygen radicals play a major role in tissue damage. In this study, the role of the vasodilation effect of Nikardipine, a calcium channel blocker, in preventing ischemia and reperfusion injury in rats exposed to acute limb ischemia was investigated. Materials and Methods: In this study, 24 Wistar Albino rats with an average weight of 200-400 g were randomly divided into 4 groups. Only subcutaneous incisions were made in the control group (n = 6) rats. Ischemia was induced by clamping the infrarenal abdominal aorta for 60 minutes in ischemia-reperfusion (IR) group (n = 6) rats, then reperfusion was performed for 120 minutes by removing the clamps. Ischemia-reperfusion (IR) + low dose nicardipine (n = 6) group rats were initiated 4 days before the surgical procedure and administered a single dose of nicardipine daily intraperitoneally. Ischemia-reperfusion (IR) + high-dose nicardipine (n = 6) group rats were started 4 days before the surgical procedure and administered a single dose of nicardipine daily intraperitoneally. After the nicardipine treatment was completed, ischemia was created by clamping the infrarenal abdominal aorta for 60 minutes in rats, then reperfusion was performed for 120 minutes by removing the clamps. When the reperfusion period was over, all rats, including the control group, were sacrificed and appropriate blood samples were taken, quadriceps muscle tissue was removed for evaluation and stored under appropriate conditions. Investigations were made in serum, muscle tissue and aorta; changes in monoclonal antibodies related to prooxidant-antioxidant system and inflammation are investigated in particular. In this context, HIF-1 alpha antibody, ICAM-1 Antibody, VCAM-1 Antibody, MMP-3 and MMP-9 antibody, Rat myeloperoxidase (MPO), Rat signal transducer and activator of Transcription 1 (STAT1), Rat mitogen activated protein kinase (MAPK) , Glutathione Peroxidase (GSH-PX), reactive oxygen species (ROS), malondialdehyde (MDA), advanced oxidation products of proteins (AOPP) and antioxidant activity (FRAP), Total-SH, Superoxide dismutase (SOD) and Catalase were studied. Results: In the biochemical examinations, it was observed that there was no difference in SODs, GSH-Px and catalase enzymes in the sera of rats for which ischemia/reperfusion model was created. While the MPO activity levels increased significantly in ischemia and it also decreased significantly in the treatment groups. A significant increase in MAPK and STAT1 levels with ischemia and a significant decrease with treatment were detected. Serum ROS, MDA, Total SH and AOPP levels increased significantly with ischemia, and FRAP levels decreased. In the treatment groups, while MDA and FRAP decreased significantly, ROS, TotalSH and AOPP did not change. Conclusion: In conclusion, we were able to create ischemia-reperfusion injury in the lower extremity in the IR group and we can say that nicardipine treatment has a protective effect against this damage.