Protective effect of aminoguanidine against cardiovascular toxicity of chronic doxorubicin treatment in rats.
The cardiotoxicity-induced by chronic treatment of doxorubicin have recently be attributed to free radical formation and/or release of nitric oxide. In the present study, an already established rat model of doxorubicin -induced cardiotoxicity was used. Doxorubicin in a total cumulative dose of 15 mgkg(-1) I.P. given in six equal injections over two week period was administered. After three weeks of doxorubicin administration, the blood pressure, serum lactate dehydrogenase, lipid peroxides, asites fluid and mortality rate were significantly increased. Doxorubicin-induced cardiotoxicity was further confirmed by examining the histopathology of heart sections. Myocardial fibres necrosis with prominent acute inflammatory cells were observed in rats hearts treated with doxorubicin. Aminoguanidine, an inhibitor of nitric oxide synthase, 100 mgkg(-1) injected every other day for two week was given concurrently with doxorubicin. Aminoguanidine given concurrently with doxorubicin return blood pressure, lactate dehydrogenase and lipid peroxides to normal control values. Furthermore, aminoguanidine reduces the mortality rate, ascites fluid formation- induced by doxorubicin and improved the histopathology of rats hearts treated with doxorubicin. In conclusion, inhibition of nitric oxide formation may be beneficial in protecting rat hearts against doxorubicin- induced cardiotoxicity.
Mostafa
A M
AM
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Nagi
M N
MN
Al Rikabi
A C
AC
Al-Shabanah
O A
OA
El-Kashef
H A
HA
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D006146:Guanidines; D008315:Malondialdehyde; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; C004479:pimagedine