Investigating the effects of ketoprofenon reperfusion related skeletal muscle injury which occurred in lower extremity experimental ischemia/reperfusion model

Aim: Ischemia/reperfusion injury in skeletal muscles can be fixed byantioxidant agents which binds free oxygen radicals. Non-steroidal anti-inflammatory drugs are the most widely used agents for this purpose, due to their analgesic and anti-inflammatory effects. Aim of this study is to investigate the effects of Ketoprofen, which is a non-steroidal anti-inflammatory drug (NSAID), on oxidative stress and changes in histopathology of the skeletal muscle (gastrocnemius muscle) seen after unilaterally clamping of femoral artery and femoral vein. Materials and Methods: 21 SpraqueDawley breed female rats were used in this study. Rats were divided into three groups, each consisted of seven rats, as follows: Group 1 (control), Group 2 (ischemia/reperfusion), Group 3 (ischemia/reperfusion + Ketoprofen). Via intraperitoneal route anesthesia with ketamine HCl 60mg/kg + xylazineHCl 10mg/kg was administered to all rats at the end offasting for 12 hours. Following aseptic skin preparation, femoral artery and vein were dissected in right hind limbafter passing through cutaneous and subcutaneous tissues. Ischemia was achieved by tourniqueting femoral artery and vein with non-traumatic surgical vessel loop. 60 minutes of revascularization was performed right after 120 minutes of ischemia. In ischemia/reperfusion + Ketoprofen group a dose of 25mg/kg Ketoprofen was administered intraperitoneally on the 60th and 90th minutes of ischemia period. Then blood and right hind limb gastrocnemius muscle samples were obtained. Superoxide dismutase andmalondialdehyde levels were studied biochemically in the serum and gastrocnemius muscle tissue samples whereas muscle fiber irregularity, hemorrhage and increase of inflammatory cells were studied in gastrocnemius muscle samples. IBM SPSS Statistics version 22 for Windows 10.0 was assigned for the evaluation of statistical analysis. One-way ANOVA test was conducted to determine the significant differences between the groups regarding the biochemical and histopathological findings. When studying the difference in-between groups, Scheffe Multiple Comparison test was used to reveal which groups resulted in the significance. P value below 0.05 was considered as statistically significant. Results: A significant difference was observed between ischemia/reperfusion group and ischemia/reperfusion + Ketoprofen group regarding the serum superoxide dismutase and tissue superoxide dismutase levels (p=0.003, p=0.029). Even though no difference was noted between control, ischemia/reperfusion and ischemia/reperfusion + Ketoprofen groups when they were compared regarding serum malondialdehyde and tissue malondialdehyde levels; a close to significance result was seen especially between ischemia/reperfusion and ischemia/reperfusion + Ketoprofen groups when tissue malondialdehyde levels were taken into account (p=0.052). In histopathological evaluation findings about muscle fiber irregularity, hemorrhage and increase in inflammatory cell counts inflammation and hemorrhage were found to decrease in ischemia/reperfusion + Ketoprofen group; and also there was a significant difference between the groups (p=0.013, p=0, p=0.005). Those biochemical and histopathological findings of our study are consistent with the literature. Conclusion: As a result; in our study Ketoprofen, an NSAID, was found to have favorable effects on skeletal muscle ischemia/reperfusion injury and was shown to be useful in ischemia/reperfusion injury. More experimental studies and clinical trials are needed to reveal these findings and to adapt in clinical practice.