Analysis of isoproterenol-induced changes in gastrocnemius muscle and serum lactate dehydrogenase expression in mice

Beta-adrenergic agonists are highly abused by sportspeople for their muscle anabolic and lipolytic effects. Muscle growth effects are thought to result from beta-2 adrenoceptor activation. This study attempted to characterise muscle (gastrocnemius) tissue damage following the administration of isoproterenol.

Adult male Balb-C mice were treated with a single oral dose of isoproterenol (100 mg/kg body weight) for 4, 8, 20, 48 and 72 hours. Control mice received equal doses of saline. The animals were killed at the respective stages, followed by the collection of gastrocnemius and blood. Serum was then separated from blood. Histopathology and lactate dehydrogenase (LDH) assays were performed.

Beta-adrenoceptor activation-induced histological changes began with structural aberrations, and ultimately resulted in myonecrosis and extensive degeneration within hours of the administration of isoproterenol. The effects of beta-agonist administration on muscle myofibre organisation were visible within four hours and became most prominent at 20 and 48 hours. Augmentation of more than 20 percent in muscle LDH activity was observed at 4, 8 and 72 hour stages, and was accompanied by a significant decline of 19 and 27 percent at 20 and 48 hour time points, respectively. Serum corroborated the above results.

Isoproterenol treatment produced considerable histopathological changes, including myonecrosis in mice gastrocnemius, resulting in a leaky sarcolemma and the release of marker enzyme, LDH into the serum (more evident after 20 and 48 hours). This suggests that isoproterenol promotes the process of necrosis in mice gastrocnemius at the concentration employed, which raises a significant question regarding the use and abuse of beta-agonists.