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.
Hrelia
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Dipartimento di Biochimica G. Moruzzi, University of Bologna, Bologna, Italy. hrelia@biocfarm.unibo.it
Bordoni
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A
Biagi
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D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D017962:alpha-Linolenic Acid / Q000378:metabolism; D017965:gamma-Linolenic Acid / Q000502:physiology*
D000970:Antineoplastic Agents; D005231:Fatty Acids, Unsaturated; D017962:alpha-Linolenic Acid; D017965:gamma-Linolenic Acid; D004317:Doxorubicin