Doxorubicininduced chemomyectomy effects in rat skeletal muscle

Emre Cullu, Ilhan Ozkan, Nil Cuhaci, Bulent Alparslan, Emel Dikicioglu, S. Oner Savk,

Abstract

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).\nMethods: 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.\nResults: 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.\nConclusion: 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.

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