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 the 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 linoleic acid (So-1100, Scotia Pharmaceuticals), at two dose levels, or an oil containing linoleic acid, but no GLA (So-1129) by oral gavage. Other groups of rats received water as a control. One of the groups of rats that received water also received i.v. ICRF-187 (60 mg/kg) 15 min prior to DOX. A group of animals acted as age-matched controls. The maximum reduction in body 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-187 (5.6±0.43%). Animals receiving 2 ml of either So-1100 or So-1129 were the least affected (≈2.5%). Measurements of cardiac volume output made at various intervals after DOX administration indicated a ≈35% reduction in cardiac function in the control and So-1129 oil group after 20 weeks. The corresponding reduction in the groups receiving ICRF-187 and 2 ml of So-1100 was ≈16%. The group receiving daily doses of 1 ml So-1100 showed an intermediate response. The death of an animal with signs of congestive cardiac failure occurred 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 ml of So-1100. It was concluded that an oil containing GLA (So-1100) has similar cardioprotective properties against DOX-induced cardiotoxicity as ICRF-187, but with less general toxicity in this rat model.