Modification of doxorubicin-induced cardiotoxicity: effect of essential fatty acids and ICRF-187 (dexrazoxane)

The capacity of an oil, containing gamma-linolenic acid (GLA), to reduce th e severity of doxorubicin-induced cardiotoxicity has been investigated in a rat model. Groups of 12-week-old, male, Sprague-Dawley rats were injected intravenously (i.v.) with single doses (3 mg/kg body weight) of doxorubicin (DOX). Daily for 1 week prior to DOX administration and for up to 20 weeks afterwards groups of rats received either an oil containing both GLA and l inoleic acid (So-1100, Scotia Pharmaceuticals), at two dose levels, or an o il containing linoleic acid, but no GLA (So-1129) by oral gavage. Other gro ups of rats received water as a control. One of the groups of rats that rec eived water also received i.v. ICRF-187 (60 mg/kg) 15 min prior to DOX. A g roup of animals acted as age-matched controls. The maximum reduction in bod y weight in the first 2 weeks after the administration of DOX. was used as a measure of acute toxicity. This was most severe in the group receiving a combination of DOX and ICRF-LS7 (5.6 +/-0.43%). Animals receiving 2 mi of e ither So-1100 or So-1129 were the least affected (approximate to2.5%). Meas urements of cardiac volume output made at various intervals after DOX admin istration indicated a approximate to 35% reduction in cardiac function in t he control and So-1129 oil group after 20 weeks. The corresponding reductio n in the groups receiving ICRF-187 and 2 mi of So-1100 was approximate to 1 6%. The group receiving daily doses of 1 mi So-1100 showed an intermediate response. The death of an animal with signs of congestive cardiac failure o ccurred in 40% of the animals in the DOX only control (water) group. There were no deaths in the groups of rats receiving either ICRF-187 or pre- and post-administration of 2 mi of So-1100. It was concluded that an oil contai ning GLA (So-1100) has similar cardioprotective properties against DOX-indu ced cardiotoxicity as ICRF-187, but with less general toxicity in this rat model. (C) 2001 Published by Elsevier Science Ltd.