Role of gamma-linolenic acid in counteracting doxorubicin-induced damage in cultured rat cardiomyocytes

The clinical usefulness of doxorubicin is limited by cardiotoxicity. We have demonstrated that doxorubicin has a dual negative effect on myocardial lipids, acting against highly unsaturated fatty acids (HUFAs) directly and desaturating/elongating enzymes required for their biosynthesis, thus decreasing linoleic and alpha -linolenic conversion to higher metabolites. Primary cultures of rat cardiomyocytes were challenged with different doxorubicin concentrations and doxorubicin exposure was followed by a 24-h recovery period in the absence or presence of serum, and of gamma -linolenic acid. Serum in the recovery medium did not appear to be essential for the restoration of the desaturating/elongating activities, and gamma -linolenic acid supplementation influenced only alpha -linolenic acid conversion. Serum, and particularly gamma-linolenic acid, were very important in increasing HUFA levels behind the pure biosynthesis. HUFA biosynthesis plays a role in counteracting doxorubicin toxicity, but it cannot completely overcome the depletion of these fatty acids; serum and exogenous gamma-linolenate are critical in filling the decreased HUFA pool.