Tags

Type your tag names separated by a space and hit enter

Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats.
Life Sci 1999; 65(12):1265-74LS

Abstract

Carvedilol (CAR) is a vasodilating beta-blocker which also has antioxidant properties. CAR produces dose-related reduction in mortality in patients with congestive heart failure. In the present study, we tested the hypothesis that CAR protects against doxorubicin (DOX)-induced cardiomyopathy in rats. Sprague-Dawley rats were treated with DOX, CAR, CAR+DOX, or atenolol (ATN)+DOX. DOX (cumulative dose, 15 mg/kg) was administered intraperitoneally, and CAR (30 mg/kg daily) or ATN (150 mg/kg daily) was administered orally. Three weeks after the completion of these treatments, cardiac performance and myocardial lipid peroxidation were assessed. Mortality was observed in the DOX (25%) and ATN+DOX (12.5%) groups. Compared with control rats, DOX significantly decreased systolic blood pressure (104+/-4 vs. 120+/-4 mmHg, P<0.05) and left ventricular fractional shortening (38.8+/-3.1 vs. 55.4+/-1.3%, P<0.01), and resulted in a significant accumulation of ascites (14.4+/-4.9 vs. 0 ml, P<0.01). CAR significantly prevented the cardiomyopathic changes caused by DOX, while ATN did not. The myocardial thiobarbituric acid reactive substances (TBARS) content was significantly higher in DOX-treated rats than in control rats (80.4+/-7.1 vs. 51.5+/-1.2 nmol/g heart, p<0.01). CAR prevented the increase in TBARS content (48.8+/-3.0 nmol/g heart, P<0.01 vs. DOX group), whereas ATN had no significant effect (74.3+/-5.2 nmol/g heart). CAR also significantly prevented the increase in both myocardial and plasma cholesterol concentrations caused by DOX. These data indicate that CAR protects against DOX-induced cardiomyopathy and that this effect may be attributed to the antioxidant and lipid-lowering properties of CAR, not to its beta-blocking property.

Authors+Show Affiliations

Internal Medicine II, Nagoya University School of Medicine, Japan. hideom@tsuru.med.nagoya-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10503942

Citation

Matsui, H, et al. "Protective Effects of Carvedilol Against Doxorubicin-induced Cardiomyopathy in Rats." Life Sciences, vol. 65, no. 12, 1999, pp. 1265-74.
Matsui H, Morishima I, Numaguchi Y, et al. Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats. Life Sci. 1999;65(12):1265-74.
Matsui, H., Morishima, I., Numaguchi, Y., Toki, Y., Okumura, K., & Hayakawa, T. (1999). Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats. Life Sciences, 65(12), pp. 1265-74.
Matsui H, et al. Protective Effects of Carvedilol Against Doxorubicin-induced Cardiomyopathy in Rats. Life Sci. 1999;65(12):1265-74. PubMed PMID: 10503942.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats. AU - Matsui,H, AU - Morishima,I, AU - Numaguchi,Y, AU - Toki,Y, AU - Okumura,K, AU - Hayakawa,T, PY - 1999/9/30/pubmed PY - 1999/9/30/medline PY - 1999/9/30/entrez SP - 1265 EP - 74 JF - Life sciences JO - Life Sci. VL - 65 IS - 12 N2 - Carvedilol (CAR) is a vasodilating beta-blocker which also has antioxidant properties. CAR produces dose-related reduction in mortality in patients with congestive heart failure. In the present study, we tested the hypothesis that CAR protects against doxorubicin (DOX)-induced cardiomyopathy in rats. Sprague-Dawley rats were treated with DOX, CAR, CAR+DOX, or atenolol (ATN)+DOX. DOX (cumulative dose, 15 mg/kg) was administered intraperitoneally, and CAR (30 mg/kg daily) or ATN (150 mg/kg daily) was administered orally. Three weeks after the completion of these treatments, cardiac performance and myocardial lipid peroxidation were assessed. Mortality was observed in the DOX (25%) and ATN+DOX (12.5%) groups. Compared with control rats, DOX significantly decreased systolic blood pressure (104+/-4 vs. 120+/-4 mmHg, P<0.05) and left ventricular fractional shortening (38.8+/-3.1 vs. 55.4+/-1.3%, P<0.01), and resulted in a significant accumulation of ascites (14.4+/-4.9 vs. 0 ml, P<0.01). CAR significantly prevented the cardiomyopathic changes caused by DOX, while ATN did not. The myocardial thiobarbituric acid reactive substances (TBARS) content was significantly higher in DOX-treated rats than in control rats (80.4+/-7.1 vs. 51.5+/-1.2 nmol/g heart, p<0.01). CAR prevented the increase in TBARS content (48.8+/-3.0 nmol/g heart, P<0.01 vs. DOX group), whereas ATN had no significant effect (74.3+/-5.2 nmol/g heart). CAR also significantly prevented the increase in both myocardial and plasma cholesterol concentrations caused by DOX. These data indicate that CAR protects against DOX-induced cardiomyopathy and that this effect may be attributed to the antioxidant and lipid-lowering properties of CAR, not to its beta-blocking property. SN - 0024-3205 UR - https://www.unboundmedicine.com/medline/citation/10503942/Protective_effects_of_carvedilol_against_doxorubicin_induced_cardiomyopathy_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024320599003628 DB - PRIME DP - Unbound Medicine ER -