2-o-octadecylascorbic-acid and Cardiomyopathies

Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization.. To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization.. We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization.

Topics: Allopurinol; Animals; Ascorbic Acid; Body Water; Cardiomyopathies; Coronary Disease; Dogs; Edema; Embolism; Free Radical Scavengers; Free Radicals; Microcirculation; Microspheres; Oxygen; Superoxide Dismutase; Theophylline

Adriamycin (ADR) is effective against a wide range of human neoplasms. However, its clinical use is compromised by serious cardiac toxicity, possibly through induction of peroxidation in cardiac lipids. Ascorbic acid, a potent antioxidant, was examined for effect in reducing ADR toxicity in mice and guinea pigs. Ascorbic acid had no effect on the antitumor activity of ADR in mice inoculated with leukemia L1210 or Ehrlich ascites carcinoma, but it significantly prolonged the life of animals treated with ADR. ADR elevated lipid peroxide levels in mouse heart, and ascorbic acid prevented the elevation. The significant prevention of ADR-induced cardiomyopathy in guinea pigs by ascorbic acid was proved by electron microscopy. Ascorbic acid and the derivatives may delay general toxicity of ADR and also prevent the cardiac toxicity. The results also suggest the clinical efficacy of the combined treatment of ADR and ascorbic acid or the derivatives.

Topics: Animals; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Cardiomyopathies; Doxorubicin; Guinea Pigs; Leukemia, Experimental; Lipid Peroxides; Mice; Mice, Inbred Strains; Myocardium; Neoplasm Transplantation