Myotoxic effects of clenbuterol in the rat heart and soleus muscle
Jatin G. Burniston1, Yeelan Ng1, William A. Clark2, John Colyer3, Lip-Bun Tan4, and David F. Goldspink1
1 Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 2ET; Departments of 3 Biochemistry and Molecular Biology and 4 Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom; and 2 Michael Reese Hospital and Medical Center, Chicago, Illinois 60616-3990
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 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.
Although the dose stated in this abstract is very high, the lower doses used in the study when corrected for rat-human metabolism (Kleiber's Law) still show damage to skeletal muscle and potentially cardiac muscle in doses commonly used by human physique competitors (100 + ug/d).
W6
Jatin G. Burniston1, Yeelan Ng1, William A. Clark2, John Colyer3, Lip-Bun Tan4, and David F. Goldspink1
1 Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 2ET; Departments of 3 Biochemistry and Molecular Biology and 4 Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom; and 2 Michael Reese Hospital and Medical Center, Chicago, Illinois 60616-3990
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 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.
Although the dose stated in this abstract is very high, the lower doses used in the study when corrected for rat-human metabolism (Kleiber's Law) still show damage to skeletal muscle and potentially cardiac muscle in doses commonly used by human physique competitors (100 + ug/d).
W6