Myotoxic effects of clenbuterol in the rat heart and soleus muscle.
Myocyte-specific necrosis in the heart and soleus muscle of adult male Wistar rats was investigated in response to a single subcutaneous injection of the anabolic beta(2)-adrenergic receptor agonist clenbuterol. Necrosis was immunohistochemically detected by administration of a myosin antibody 1 h before the clenbuterol challenge and quantified by using image analysis. Clenbuterol-induced myocyte necrosis occurred against a background of zero damage in control muscles. In the heart, the clenbuterol-induced necrosis was not uniform, being more abundant in the left subendocardium and peaking 2.4 mm from the apex. After position (2.4 mm from the apex), dose (5 mg clenbuterol/kg), and sampling time (12 h) were optimized, maximum cardiomyocyte necrosis was found to be 1.0 +/- 0.2%. In response to the same parameters (i.e., 5 mg of clenbuterol and sampled at 12 h), skeletal myocyte necrosis was 4.4 +/- 0.8% in the soleus. These data show significant myocyte-specific necrosis in the heart and skeletal muscle of the rat. Such irreversible damage in the heart suggests that clenbuterol may be damaging to long-term health.
Burniston
Jatin G
JG
Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 2ET, United Kingdom. hhsjburn@livjm.ac.jp
Ng
Yeelan
Y
Clark
William A
WA
Colyer
John
J
Tan
Lip-Bun
LB
Goldspink
David F
DF
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000506:poisoning*; D000818:Animals; D002976:Clenbuterol / Q000008:administration & dosage / Q000506:poisoning*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D007279:Injections, Subcutaneous; D007441:Intubation, Gastrointestinal; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D002976:Clenbuterol