Therapeutic comparison of MitoTEMPO and rosmarinic acid as mitochondria targeted and non targeted antioxidants evaluated in rat sciatic nerve crush injury model

Mitochondria are key organelles involved in various pathophysiological processes. As the primary site of reactive oxygen species (ROS) production, they represent a major target for many therapeutic agents. In this study, the therapeutic effects of a mitochondria-targeted antioxidant (MitoTEMPO, MT) and a conventional yet potent antioxidant compound (rosmarinic acid, RA) were compared in a rat model of sciatic nerve crush injury, focusing on nerve conduction parameters and histological structures. A total of 28 adult Wistar Albino rats were used in the study, with seven animals assigned to each group: SHAM, crush injury (CI), RA, and MT. The CI model was induced by applying a mosquito-type clamp to the sciatic nerve for 40 s. Nerve conduction parameters were evaluated using compound action potentials (CAPs) analyzed through comprehensive mathematical methods. In addition, structural alterations were assessed via histological staining and scoring. Both RA and MT treatments exerted therapeutic effects on the CAP parameters, which were progressively suppressed by CI. However, the efficacy of MT was more pronounced-particularly in nerve fibers with conduction velocities between 65 and 69 m/s, where significant improvements were observed. Histological evaluation of CI group preparations revealed neuronal loss between nerve fascicles, axonal degeneration, increased collagen deposition, cytoplasmic vacuolization, and myelin sheath degeneration. MT treatment was more effective than RA in alleviating these pathological alterations. In conclusion, this study underscores the importance of mitochondria-targeted antioxidant strategies in reversing electrophysiological suppression and structural damage following peripheral nerve injury.