Differential long-term subcellular responses in heart and liver to adriamycin stress. Exogenous L-carnitine cardiac and hepatic protection.
In order to evaluate the heart and liver responses after adriamycin (ADR) toxic aggression, with and without exogenous L-carnitine (CAR) protection, female Sprague-Dawley rats, body weight 40-60 g, were randomized into four groups: CON, ADR, CAR and CAR-ADR. ADR was injected i.v. at a dose of 15-18 mg/kg body wt (0.1 ml). CAR was administered i.v. at a dose of 20 mg (0.1 ml) before each subdose of ADR, and then orally at 180 mg/kg body wt daily for 12 weeks. Long-term cardiac and hepatic subcellular damage were determined by transmission electron microscopic analysis of ultrathin sections. The ADR-induced long-term cardiac subcellular pathology included loss, disruption and disassembly of myofibrils, and mitochondrial swelling and condensation. On the other hand, the ADR-induced subcellular hepatic alterations consisted of polymorphic mitochondria, cytoplasmic vacuolization and accumulation of lipid droplets. Apparently, cardiac tissue was more affected by ADR toxic aggression than hepatic tissue. However, these alterations were of less severity in protected groups, in both heart and liver, suggesting CAR as a possible hepatoprotector agent against ADR toxicity. Because of the liver-L-carnitine-heart relationship, studying ADR-hepatotoxicity could be helpful in the further understanding of severe ADR-cardiotoxicity.
Zeidán
Q
Q
Section of Cellular Biology, Institute of Tropical Medicine, Faculty of Medicine, Central University of Venezuela, Caracas.
Strauss
M
M
Porras
N
N
Anselmi
G
G
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D002331:Carnitine / Q000008:administration & dosage / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D004359:Drug Therapy, Combination; D005260:Female; D006321:Heart / Q000187:drug effects*; D007275:Injections, Intravenous; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control; D008933:Mitochondrial Swelling / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009210:Myofibrils / Q000187:drug effects / Q000648:ultrastructure; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
D000970:Antineoplastic Agents; D020011:Protective Agents; D004317:Doxorubicin; D002331:Carnitine