AZT dilates rat cardiac intercalated discs, and the effect is prevented by vitamin C

Abstract

We investigated whether chronic zidovudine (AZT) administration in rats could impair cardiac function by affecting intercellular junctions and whether vitamin C could prevent these possible effects. Rats were treated for 8 months with AZT, vitamin C, and AZT plus vitamin C. Cardiac fractional shortening (FS) was assessed by echocardiographic examination, intercellular junctions morphology was detected by electron microscopy (EM) and immunocytochemistry (ICC). AZT-treated rats showed a reduced FS that was not prevented by vitamin C. EM revealed that AZT treatment did not affect coronary endothelial intercellular junctions whereas it caused an enlargement of fascia adherens of the intercalated discs that was prevented by vitamin C. AZT treatment did not induce either alterations of gap junctions morphology or distribution of connexin-43, the major protein expressed in the gap junctions. We conclude that AZT treatment may be potentially deleterious to the heart by inducing a ROS-mediated damage of cardiac intercalated discs.