K-7259, A NOVEL DILAZEP DERIVATIVE, AND D-PROPRANOLOL ATTENUATE H2O2-INDUCED CELL-DAMAGE

We studied the effects of dilazep, K-7259 (a novel derivative of dilaz ep) and d-propranolol on the change in cell shape and accumulation of nonesterified fatty acids (NEFA) induced by hydrogen peroxide (H2O2) i n isolated rat cardiac myocytes. Myocytes were incubated in a Krebs-Ri nger bicarbonate buffer containing 2 mM diethyltriamine pentaacetic ac id (DETAPAC) and 2 mM FeSO4 for 10 min, and then treated with 2 mM H2O 2 for 50 min. Before the treatment with H2O2, the percentage of the nu mber of rod-shaped cells to that of total cells was 66 +/- 2%, and dec reased to 35 +/- 3%, 25 +/- 4% and 14 +/- 2%, after 30, 40 and 50 min of the H2O2 treatment, respectively. The levels of NEFA (lauric, myris tic, palmitoleic, arachidonic, linoleic, palmitic, oleic and stearic a cids) increased after the treatment with H2O2. In the absence of FeSO4 and DETAPAC, however, H2O2 did not have these effects, and therefore all the experiments with drugs were performed in the presence of Fe2SO 4 and DETAPAC. K-7259 (30 mu M) and d-propranolol (50 mu M) attenuated both the changes in cell shape and accumulation of NEFA induced by H2 O2, whereas dilazep (30 or 50 mu M) did not. N-(2-mercaptopropionyl)gl ycine (2 mM), an . OH scavenger, inhibited the H2O2-induced changes co mpletely. These results suggest that K-7259 and d-propranolol attenuat e the H2O2-induced changes in cell shape and accumulation of NEFA, pro bably because of their . OH-scavenging effect.