Androgenic-Anabolic Steroids Associated With Mechanical Loading Inhibit Matrix Metallopeptidase Activity and Affect the Remodeling of the Achilles Tendon in Rats

¹ Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, Brazil
² Departamento de Fisioterapia, Universidade Federal de São Carlos, São Carlos, Brazil
³ Departamento de Fisiologia e de Clínica Médica da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil

^* To whom correspondence should be addressed. E-mail: hsaraujo{at}power.ufscar.br.

	Abstract

Background: The indiscriminate use of anabolic-androgenic steroids has been shown to induce pathologic changes in the Achilles tendon in several situations.

Purpose: To study tendon remodeling in rats treated with anabolic-androgenic steroids combined with an exercise program.

Study Design: Controlled laboratory study.

Methods: Wistar rats were grouped as follows: sedentary (group I), injected with anabolic-androgenic steroids only (group II), trained only (group III), and trained and injected with anabolic-androgenic steroids (group IV). The trained groups performed jumps in water: 4 series of 10 jumps each, with an overload of 50% to 70% of the animal’s body weight and a 30-second rest interval between series, for 6 weeks. Anabolic-androgenic steroids (5 mg/kg) were injected subcutaneously. Activity of matrix metallopeptidases, a marker for tendon remodeling, was analyzed in tissue extracts by zymography on gelatin-sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Results: Morphological analyses of tendons showed that in group II, the most external layer that covers the tendon was thicker with aggregation of the collagen fibers, suggesting an increase in collagen synthesis. In group IV, an inflammatory infiltrate and fibrosis in tendons as well as a pronounced increase of the serum corticosterone level were observed. This training protocol upregulated matrix metallopeptidase activity, whereas anabolic-androgenic steroid treatment strongly inhibited this activity. The appearance of lytic bands with molecular masses of approximately 62 and 58 kDa suggests the activation of matrix metallopeptidase-2.

Conclusion: Anabolic-androgenic steroid treatment can impair tissue remodeling in the tendons of animals undergoing physical exercise by downregulating matrix metallopeptidase activity, thus increasing the potential for tendon injury.

Clinical Relevance: Since the AAS abuse is so widespread, a better comprehension of the pathological effects induced by these drugs may be helpful for the development of new forms of therapy of AAS-induced lesions.

Key Words: androgenic-anabolic steroids, tendon, matrix metallopeptidase (MMP), corticosterone, remodeling