INHIBITION OF CALCIUM ACCUMULATION BY THE SARCOPLASMIC-RETICULUM - A PUTATIVE MECHANISM FOR THE CARDIOTOXICITY OF ADRIAMYCIN

The aim of this study was to examine the effect of adriamycin (ADR) on calcium accumulation by the sarcoplasmic reticulum (SR). Chemical ski nning of cultured rat myocardial cells compromised the barrier functio n of the cell membrane and thus permitted direct exposure of mitochond rial and non-mitochondrial sites to ADR. In the presence of ATP, and s odium azide, mitochondrial calcium accumulation was negligible. Furthe rmore, it has previously been shown that non-mitochondrial calcium acc umulation is mediated mainly by the SR under these conditions. Incubat ion with 10 mu M ADR for 2 hr reduced the level of calcium accumulatio n by the SR by 50%. A similar effect was obtained after 24 hr incubati on with 1 mu M ADR. The addition of ferric iron to the culture medium further reduced the level of calcium accumulation. Neither Vitamin E n or beta-carotene affected calcium accumulation by the SR. These result s suggest that ADR interferes with the calcium accumulation activity o f the SR and that ferric iron potentiates this effect. (C) 1997 Elsevi er Science Inc.