ANABOLIC-ANDROGENIC STEROID-INDUCED TOXICITY IN PRIMARY NEONATAL RAT MYOCARDIAL-CELL CULTURES

Recent literature reports of myocardial infarction in athletes who sel f-administer anabolic-androgenic steroids (AAS) and previous animal st udies of the effects of AASs on the heart suggest that these drugs may be directly injurious to the myocardium. We have previously demonstra ted that 100 mu M testosterone cypionate (TC) inhibits all beating act ivity of primary neonatal rat myocardial cell cultures within 1 hr of exposure and causes significant LDH release by 4 hr of exposure, indic ating a direct toxic effect of TC. The purpose of this investigation w as to evaluate the effects of commonly abused AASs on primary neonatal rat myocardial cell cultures and to provide insight into early cellul ar changes that may lead to TC-induced toxicity. Significant LDH relea se was observed in 5-day-old primary myocardial cell cultures (obtaine d from 3- to 5-day-old Sprague-Dawley rats) exposed to 100 mu M testos terone enanthate (TE), testosterone propionate (TP), and oxymetholone (O) for 4 and 24 hr and in cultures exposed to 100 mu M testosterone ( T) for 24 hr. Neutral red retention and MTT formazan production were s ignificantly decreased in cell cultures exposed to 100 mu M TE, TP, an d O after only 4 hr of exposure, indicating a loss of viability and mi tochondrial activity. However, there was no effect on viability of cel l cultures exposed for 24 hr to 100 mu M Of a variety of other commonl y abused AASs. Phase-contrast microscopy revealed complete disruption of the monolayer in cell cultures treated with 100 mu M TE, TP, and O for 4 hr. Treatment of fura-2-loaded myocardial cell cultures with 100 mu M TC produced no significant changes in calcium transients or base line calcium levels for up to 13 min of exposure. These results indica te that O, T, TC, TE, and TP produce a direct toxic effect in heart ce ll cultures and that early(<l3 min) changes in calcium homeostasis are unlikely to participate in the mechanism of toxicity. (C) 1995 Academ ic Press, Inc.