?-Agonist-induced alterations in organ weights and protein content: Comparison of racemic clenbuterol and its enantiomers

Abstract

Clenbuterol is a relatively selective beta2-adrenergic partial agonist that has bronchodilator activity. This drug has been investigated as a potential countermeasure to microgravity- or disuse-induced skeletal muscle atrophy because of presumed anabolic effects. The purpose of this study was to: 1) analyze the anabolic effect of clenbuterol's (-)-R and (+)-S enantiomers (0.2 mg/kg) on muscles (cardiac and skeletal) and other organs; and 2) compare responses of enantiomers to the racemate (0.4 mg/kg and 1.0 mg/kg). Male Sprague Dawley rats were treated with: a) racemic clenbuterol (rac-clenbuterol, 0.4 or 1.0 mg/kg); b) enantiomers [clenbuterol (-)-R or (+)-S]; or c) vehicle (1.0 mL/kg buffered saline). Anabolic activity was determined by measuring tissue mass and protein content. HPLC teicoplanin chiral stationary phase was used to directly resolve racemic clenbuterol to its individual enantiomers. In skeletal muscle, both enantiomers had equal anabolic activity, and the effects were muscle- and anatomic region-specific in magnitude. Although the enantiomers did not affect the ventricular mass to body weight ratio, clenbuterol (+)-S induced a small but significant increase in ventricular mass. Both clenbuterol enantiomers produced significant increases in skeletal muscle mass, while being less active in producing cardiac ventricular muscle hypertrophy than the racemic mixture.

Effects of clenbuterol enantiomers on growth of young male rats

“…It suggests that both CB enantiomers were actively anabolic to striated muscle without much difference. These results were almost the same as the data of von Deutsch et al 8) using high dose rac-CB (1mg/kg) despite an age difference. The anabolic effect on muscles might depend on various mechanisms of hypertrophy like the balance of protein synthesis and proteolysis, and might be different from the effects on bone.…”

“…CB is well known as a lipolytic agent 22,23) . In the present study, the change of fat mass or liver, which is closely related to lipolysis and energy metabolism, was not examined; but von Deutsch et al 8) and Smith 24) reported that (+)-S-CB remains in higher concentration than (-)-R-CB in the liver. The liver weight of rats was negatively affected by a high dose (2.0 mg/kg daily) of CB drinking for 4 days 25) .…”

“…In the present study, the heart and skeletal muscles of the SOL and EDL showed increased weights (see Table 2) like in previous reports 8,25,26) . Cubria et al reported cardiac hypertrophy by CB in mice 27) and Duncan et al showed undesirable effects by not only cardiac hypertrophy, but also increased collagen infiltration around blood vessels and in the wall of the left ventricle 28) .…”

“…There were some contradictory reports that CB induced increased body weight 29,30) , and no change in heart and skeletal muscles of animals. The reason might be due to the difference in type 30,31) of animals, sex 12) , age 29) , administration method 24) , dose 8) , duration, etc. 21,25) Unfortunately, in this study, we had no data on the difference in amount of physical activity or the amount of dietary intake among the 3 groups.…”

“…It is important to make clear the different actions of enantiomers as seen in the case of the Thalidomide Tragedy 7) . For the first time, von Deutsch et al 8) reported that both enantiomers had equal anabolic activity in skeletal muscle of mature male rats, but was less active in cardiac muscle hypertrophy than rac-CB. Furthermore, they reported that treatment with 1.0 mg/ kg rac-CB significantly increased tibia mass, but had no effect on the femur.…”