Effects of Co-Administration of Clenbuterol and Testosterone Propionate on Skeletal Muscle in Paraplegic Mice

Abstract

Spinal cord injury (SCI) is generally associated with a rapid and significant decrease in muscle mass and corresponding changes in skeletal muscle properties. Although beta(2)-adrenergic and androgen receptor agonists are anabolic substances clearly shown to prevent or reverse muscle wasting in some pathological conditions, their effects in SCI patients remain largely unknown. Here we studied the effects of clenbuterol and testosterone propionate administered separately or in combination on skeletal muscle properties and adipose tissue in adult CD1 mice spinal-cord-transected (Tx) at the low-thoracic level (i.e., induced complete paraplegia). Administered shortly post-Tx, these substances were found to differentially reduce loss in body weight, muscle mass, and muscle fiber cross-sectional area (CSA) values. Although all three treatments induced significant effects, testosterone-treated animals were generally less protected against Tx-related changes. However, none of the treatments prevented fat tissue loss or muscle fiber type conversion and functional loss generally found in Tx animals. These results provide evidence suggesting that clenbuterol alone or combined with testosterone may constitute better clinically-relevant treatments than testosterone alone to decrease muscle atrophy (mass and fiber CSA) in SCI subjects.

Nandrolone Normalizes Determinants of Muscle Mass and Fiber Type after Spinal Cord Injury

“…In that study, fiber size was reduced by 49% by SCI for gastrocnemius, soleus, and tibialis anterior, whereas only a 30% reduction in CSA was observed for muscle fibers in SCI animals administered testosterone Thus, the findings indicated that testosterone protected against 40% of the loss that would have otherwise occurred. Testosterone was also found to increase body weight and muscle fiber CSA of the soleus and extensor digitorum longus muscles in male mice at 4 and 8 weeks after SCI (Ung et al, 2010). Of note, the mass of these muscles was not significantly altered by this agent.…”

“…The administration of testosterone to spinal cord-transected rats or mice reduced muscle atrophy as assessed by myofiber cross-sectional area (Gregory et al, 2003;Ung et al, 2010). The specific mechanisms behind this benefit are uncertain.…”

A short-term arm-crank exercise program improved testosterone deficiency in adults with chronic spinal cord injury

“…In this respect, results achieved by using testosterone replacement therapy both in animal research (5) and human studies (3) have been promising. To date, no studies have been focused on improving testosterone levels by performing an intervention program based on regular exercise in individuals with chronic SCI.…”

Functional and Physiological Effects of Treadmill Training Induced by Buspirone, Carbidopa, and L-DOPA in Clenbuterol-Treated Paraplegic Mice

“…We have previously shown that clenbuterol alone can partially increase muscle mass and size in Tx mice. 18 We now show that clenbuterol treatment combined with BCD-induced training increases muscle mass, whole muscle CSA, and single-fiber CSA values. In fact, those values were similar to those in non-Tx Figure 3.…”

“…Clenbuterol was chosen for this study based on promising muscle-building effects already shown in models of muscle wasting as well as in paraplegic mice. [14][15][16][17][18] …”