[Influence of silymarin and doxorubicin on the myocardial function in rats].
BACKGROUND
Silymarin, an extract of Silybum marianum seeds, presents a complex of flavonolignans with a broad spectrum of action: antifibrotic, antiinflammatory, lipid peroxidation inhibiting and free radical scavenging effects. A therapy of acute leukemias and lymphomas is in many cases limited with cardiotoxicity of doxorubicin. The aim of the investigation was to examine influence of interaction of silymarin 60 mg/kg, orally applied and doxorubicin 1.25 mg/kg, applied i.p. on heart function during continuous intravenous infusion of verapamil (2.5 mg/ml) and on serum activity of creatine kinase and lactate dehydrogenase in rats.


METHODS
The animals were anaesthetised with urethane and the prepared jugular vein was connected to the infusion pump with verapamil in the course of recording ECG. The ECG analyses encompassed the first heart reaction to drug infusion, more continuous reactions and toxic effect. Then animals were sacrificed by cardiopunction and blood samples were taken to determine serum enzymes activity.


RESULTS
The results show that the treatment with silymarin and doxorubicin in combination causes statistically significant increase of verapamil dose necessary to produce first change (2.21 : 0.62, p < 0.01); continuous reaction (2.77 : 1.5, p < 0.05) and toxic effect (3.38 : 1.87, p < 0.05) in comparison to the groups treated with silymarin or doxorubicin alone. The application of silymarin prevents an increase of creatine kinase activity induced with doxorubicin (279 : 616; p < 0.0l). The activity of lactate dehydrogenase was not significantlly different between the groups.


CONCLUSIONS
On the basis of the results it can be concluded that silymarin prevents toxic effects of doxorubicin on myocardial function.
Stilinović
Nebojsa
N
Medicinski fakultet, Univerzitet u Novom Sadu,
Rasković
Aleksandar
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D003402:Creatine Kinase / Q000097:blood; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000008:administration & dosage / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D012838:Silymarin; D004317:Doxorubicin; D014700:Verapamil; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase