الفهرس 
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Abstract
Introduction Paclitaxel is a widely used chemotherapy for the treatment of solid cancers such as ovarian, breast and lung carcinoma. Patients receiving this type of chemotherapy report symptoms of fatigue. It is reported that tumor-free rat models injected with this compound showed severe hindlimb muscle weakness. Melatonin is a hormone made by the pineal gland. It has a role in the biological regulation of circadian rhythms, sleep and mood. In addition, many clinical studies confirmed the beneficial role of melatonin as antiinflammatory, anti-oxidant, antidepressant, analgesic and sedative. It is efficient in scavenging free radicals and reducing oxidative damage. Moreover, it is safe and well tolerated in animals and human over wide range of doses. Aim of the Work The aim of this work was to study paclitaxel effect on the skeletal muscle and the possible protective role of melatonin in adult male albino rat using different histological methods. Materials and Methods Animal grouping: The rats were divided into four main groups as the following: group I (control group): This group included 10 rats that was subdivided into: Sub group Ia: included 5 rats that were kept without treatment. Sub group Ib: included 5 rats that were received 1ml saline (the vehicle of paclitaxel) intraperitoneally once a week for five consecutive weeks. group II: included 5 rats that were received melatonin orally (oral suspension) at a dose of 5mg/kg daily for two months. group III: included 10 rats that were received Paclitaxel intraperotineally at a dose of 16 mg/kg diluted in 1ml normal saline once a week for five consecutive weeks. group IV: included 10 rats that were received melatonin and paclitaxel concomitantly at the same doses and duration as mentioned in group II & group III. At the end of experiment, rats were anesthetized and the gastrocnemius muscle was obtained for further processing to be examined by light and electron microscopes. Results: 1- group I (control group): Light and electron microscopic examination of gastrocnemius muscles sections of group I showed normal histological structure of the skeletal muscle. Light microscopic examination of immunohistochemical stained sections of gastrocnemius muscles of group I showed apparent strong positive brownish immune-reaction for desmin. 2- group II (received melatonin): Examination of sections obtained from this group revealed the same results as in control group. 2- group III (received paclitaxel): Light microscopic examination of H&E stained sections of the gastrocnemius muscle of group III showed histological alterations with loss of the normal architecture. It showed shrunken muscle fibers. Some areas of sarcoplasm showed splitting or even complete loss. There were internalized myo nuclei. There was wide separation of endomysium and perimysium with apparent increase in their connective tissue component. Inflammatory cellular infiltration, congestion of blood vessels and hemorrhage were observed. Light microscopic examination of immunohistochemical stained sections of gastrocnemius muscles of group III showed apparent weak positive brownish immune-reaction for desmin. Electron microscopic examination of ultra-thin sections obtained from animals of group III showed severe ultra-structural alterations in the form of loss of normal banding pattern of the skeletal muscle. Lysis of myofibrils with discontinous Z lines and separated myofibrils were observed. It showed detached corrugated sarcolemma with subsarcolemmal accumulation of swollen mitochondria with loss of cristae, enlarged fused mitochondria and increased glycogen granules were observed. It also showed irregular nucleus with indented nuclear membrane and internalized myonucleus. There was vacculation of the sarcoplasm. 3- group IV (received paclitaxel and melatonin): Light microscopic examination of H&E stained sections for most of gastrocnemius muscle fibers of group IV showed normal histological architecture of skeletal muscle with preserved striations. Some fibers showed less histological alterations than group III. Light microscopic examination of immunohistochemical stained sections of gastrocnemius muscles of group IV showed apparent moderate to strong positive brownish immune-reaction for desmin. Electron microscopic examination of ultra-thin sections obtained from animals of group IV showed improved ultrastructural features of skeletal muscle with preserved banding pattern. It showed less histological alteration than group III. Conclusion from the present study it could be concluded that that paclitaxel has toxic effects on the histological structure of the skeletal muscle of adult male albino rats and melatonin could to some extent preserve the structural integrity of the skeletal muscle.