The effects of ticagrelor on viability of skeletal muscules and the levels of ADMA, MDA, GSH in a lower extremity ischemia-reperfusion model

Although successful results were obtained in various experimental studies aiming to prevent Ischemia-Reperfusion (I-R) damage, very few of them came into use clinically. In this study related with experimental lower extremity ischemia-reperfusion damage, the effects of ticagrelon, which is a new antiplatelet agent, on blood ADMA, MDA, GSH levels and skeleton muscle viability were examined. In the study, 21 male rats aged 8-10 weeks and with a weight of 250±20 gr were used. While no operation was performed on control group (n=7) infrarenal abdominal aorta (IAA) clamp was placed to ischemia-reperfusion (I-R) group (n=7) and ticagrelor group (n=7) and ischemia was applied for 2 hours and reperfusion was applied by 2 hours after removal of clamp. At the end of reperfusion, rats were sacrificed and then their soleus muscles were excised and muscle and blood tissue samples were taken. Histopathological examination was applied to tissue samples and ADMA, MDA, GSH levels were examined on blood samples. After reperfusion period on all groups, soleus muscle samples were taken for histopathological examinations. In histopathological examination, hematoxylin-eosin staining was applied to tissues and were evaluated by light microscope. Histopathological scoring was applied for determined parameters. When results were statistically evaluated, significant increase was detected in ischemia-reperfusion group compared to control group in terms of deviling loss, separation in muscle fibers and edema. However it was also determined that these increases significantly decreased in samples to which ticagrelor was applied prior to ischemia-reperfusion compared to the group to which ticagrelor was not applied. In the statistical analysis made with biochemical measurement results it was determined that the blood and muscle tissue ADMA and MDA levels significantly increased in I-R group compared to control group. This increase was less in the group to which ticagrelor was applied. There was no statistically significant difference in the ticagrelor group compared to control group. The increase in blood GSH levels was statistically significant in I-R group compared to control group. The increase in blood GSH levels was similarly statistically significant in ticagrelor group compared to control group. On the other hand significant decrease was observed in ticagrelor group compared to I-R group. The GSH level increase in muscle tissues was significant in I-R group compared to control group. In ticagrelor group the decrease was significant compared to I-R group while the increase was not significant compared to control group. As a result, in this study data was obtained that ticagrelor, which is a new antiplatelet agent, decreases oxidant level and skeleton muscle damage in lower extremity ischemia-reperfusion damage. However in order to enlighten through which mechanisms the protective effects were formed, requirement for new and more detailed experimental studies is considered. If the results of the larger scaled studies that will be made about this subject support our study, it is considered that it will provide very important benefit in daily clinical usage, decrease mortality and morbidity, shorten hospital stay periods and provide contribution to country economy. Key words: Ischemia-Reperfusion injury, ADMA, MDA, GSH, Ticagrelor