[Effects of 2,3-dimethoxy-5-methyl-6-(10'-hydroxydecyl)-1,4-benzoquinone (CV-2619) on adriamycin-induced ECG abnormalities and myocardial energy metabolism in spontaneously hypertensive rats].
Antidote actions of CV-2619 and ubiquinone-10 (Q-10) against adriamycin (ADM) cardiotoxicity were studied in spontaneously hypertensive rats. ADM (1 mg/kg/day, i.p.) elicited widening of the QRS complex in the ECG. The widening of the QRS complex was counteracted by a 10-day treatment with CV-2619 (10 and 30 mg/kg/day, p.o.) or Q-10 (10 mg/kg/day, p.o.), which was started on the 15th day of the ADM treatment. CV-2619 or Q-10, however, did not influence ADM-induced decrease in body and heart ventricular weights. Systemic hypotension caused by adriamycin was accelerated by CV-2619 or Q-10. The ADM treatment significantly decreased myocardial glycogen and glucose contents, while it did not affect the lactate content. Furthermore, ADM did not affect the myocardial content of adenine nucleotides, but significantly increased that of creatine phosphate. CV-2619 or Q-10 medication did not counteract changes in these contents by ADM. On the contrary, both agents decreased the lactate content and increased the phosphorylation potential, an index of myocardial energy state. In conclusion, CV-2619 might be as effective as Q-10 to protect the heart against ADM cardiotoxicity, and both test agents improved the myocardial energy state.
D000818:Animals; D016227:Benzoquinones; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004562:Electrocardiography; D004734:Energy Metabolism / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010756:Phosphoric Acids / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014451:Ubiquinone / Q000494:pharmacology / Q000031:analogs & derivatives
D016227:Benzoquinones; D010756:Phosphoric Acids; D011506:Proteins; D011809:Quinones; D014451:Ubiquinone; D004317:Doxorubicin; C036619:idebenone; C025204:Ubiquinone Q2