EMRE ÇULLU, İlhan ÖZKAN, Nil ÇULHACI, Bülent ALPARSLAN, Emel DİKİCİOĞLU, Ş. Öner ŞAVK

Doksorubisinin sıçan iskelet kasında kemomiyektomi etkisi

Amaç: Bu çalışmada, spastik kasta aktif kas lif sayısının azaltılmasıyla dengenin sağlanabileceği düşünülerek, doksorubisinin iskelet kasında yaratacağı kalıcı hücre kaybının (kemomiyektomi) deneysel olarak gösterilmesi amaçlandı. Çalışma planı: Wistar cinsi 18 sıçan iki gruba ayrıldı; birinci gruptaki dokuz sıçanın sol kuadriseps kasına 0.02 mg/0.5 ml, ikinci gruptaki dokuz sıçanın sol kuadriseps kasına 0.05 mg/0.5 ml doksorubisin enjekte edildi. Tüm sıçanların sağ kuadriseps kaslarına 0.5 ml serum fizyolojik enjekte edilerek kontrol grubu oluşturuldu. Her iki gruptan üçer sıçanın yaşamları 1, 6 ve 10. haftalarda sonlandırılarak her iki taraf kuadriseps kasları histolojik olarak incelendi.Bulgular : Histolojik incelemede kontrol grubunu oluşturan sağ kuadriseps kasları normal bulundu. Birinci haftada alınan örneklerde doza bağımlı olarak, ikinci grupta daha fazla olmak üzere akut enflamasyon bulguları görüldü. Birinci grupta %2.5, ikinci grupta %10 oranında enflamasyon alanı saptandı. Altıncı hafta örneklerinde, dozdan bağımsız olarak akut enflamasyon bulgularının yerini, tüm alanın ortalama %0.8'i kadar oranda rejenerasyon oluşumuna ve fibrozise bıraktığı gözlendi. On haftalık örneklerde ise rejenerasyonun bulunmadığı, hasarlı alanların (ortalama %2.5 oranı nda) fragmente olduğu, atrofik fibrillerin var olduğu ve dozdan bağımsız olarak belirgin fibrozis geliştiği saptandı. Çıkarımlar: Doksorubisinin erken dönemde doza bağımlı akut bir enflamasyona yol açtığı geç dönemde ise doza bağımlı olmaksızın kas liflerinde fragmentasyon, atrofi ve fibrozise neden olarak, kasın kasılabilir elemanlarında kalıcı bir azalmaya neden olduğu gözlendi. iskelet kasındaki bu kemomiyektomi etkisiyle, doksorubisinin spastisiteyle seyreden hastalıkların tedavisinde yeni bir kimyasal ajan olabileceği sonucuna varıldı.

Anahtar Kelimeler:

Spazm, Modeller, hayvan, Doz-yanıt ilişkisi, ilaç, Sıçan, Wistar, Kas, iskelet, Modeller, teorik, Antibiyotikler, antineoplastik, Doksorubisin

Doxorubicin-induced chemomyectomy effects in rat skeletal muscle

Objectives: This study was based on the assumption that decreased number of active muscle fibres in the spastic muscle may be associated with restoration of the balance. Hence, the effect of doxorubicin was evaluated in inducing permanent cell necrosis on skeletal muscle (chemomyectomy). Methods: Eighteen Wistar rats were divided into two groups, equal in size, to receive doxorubicin injections (0.02 and 0.05 mg/0.5 ml) into the left quadriceps muscles under general anaesthesia. The right quadriceps muscles (controls) were assigned to receive 0.5 ml of physiologic saline solution. Three rats in each group were sacrificed on the 1st, 6th, and 10th post-injection weeks, after which all the quadriceps muscles were histologically evaluated. Results: Histopathologic findings were normal in the control muscles. Dose-dependent acute inflammatory reactions were observed in both groups at the end of the first week, with a higher severity at 0.05 mg doses. The size of the inflammation areas were 2.5% and 10% at 0.02 mg and 0.05 mg doses, respectively. At the end of six weeks, acute inflammatory reactions were replaced by the development of regeneration and fibrosis accounting to 0.8% of all the areas, regardless of the dose given. Specimens of the 10th week exhibited no regeneration; there was a mean of 2.5% fragmentation within the impaired areas, with atrophic fibrils and marked fibrosis showing no dose-dependence. Conclusion: Doxorubicin induces a dose-dependent inflammatory reaction during the early postoperative period. In the long-term, permanent effects, which are not dose-dependent, are observed characterized by fragmentation, atrophy, fibrosis of muscle fibres, and losses in contractile muscle elements. These doxorubicin-induced chemomyectomy effects may prove therapeutic in the treatment of spasticity-associated diseases.

Keywords:

Spasm, Models, Animal, Dose-Response Relationship, Drug, Rats, Wistar, Muscle, Skeletal, Models, Theoretical, Antibiotics, Antineoplastic, Doxorubicin,

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