title: Doxorubicin mediated cardiotoxicity in rats: protective role of felodipine on cardiac indices.
abstract: Anthracyclines find vital uses in the treatment of solid tumors and other kind of malignancies. A typical side effect observed with few agents of this class is dose-dependent cardiotoxicity. Doxorubicin is one such agent which backs the generation of free radicals through metabolism of its quinone structure. This effect combined with induction of apoptotic and necrotic pathways leads to the development of irreversible cardiotoxicity. Reports showing the cardioprotective effects of felodipine have been published in the past. We chose to evaluate protective effect of felodipine in acute cardiotoxicity in rats induced by single dose of doxorubicin. Felodipine was assessed against doxorubicin-induced cardiotoxicity and we found that felodipine not only improves cardiac marker enzymes (P<0.001 for LDH; P<0.01 for CK-MB) but also prevents damage to myocardial tissue (20.61% necrosed area in doxorubicin intoxication; 11.52% necrosed area in felodipine treated group). Activation of apoptotic pathways is decelerated which is indicated by a significant reduction in myocardial caspase-3 activity (P<0.05) following felodipine pretreatment. Felodipine pretreatment was able to maintain normal cardiac morphology and histoarchitecture. Gravimetric analysis revealed beneficial effects following felodipine pretreatment. Abnormalities seen in the ECG after doxorubicin treatment were normalized to a significant extent (ST interval normalization was significant at P<0.01) in felodipine treated rats. In itself, felodipine was not found to have any detrimental effects on the myocardium or hemodynamic parameters of rats. Findings of the study suggest that pretreatment with felodipine prevents doxorubicin induced cardiotoxicity.
authors: Pharmacy Department, Faculty of Technology & Engineering, The Maharaja Sayajirao University of Baroda, Vadodara 390001, Gujarat, India. Electronic address: gandhihardikp@gmail.com.
authors: Hardik
authors: H
authors: Gandhi
authors: Vaibhav B
authors: VB
authors: Patel
authors: Nirav
authors: N
authors: Mistry
authors: Naeem
authors: N
authors: Patni
authors: Jatin
authors: J
authors: Nandania
authors: Ramachandran
authors: R
authors: Balaraman
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D002316:Cardiotonic Agents; D020169:Caspases / Q000378:metabolism; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004562:Electrocardiography / Q000187:drug effects; D015736:Felodipine / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D000959:Antihypertensive Agents; D000975:Antioxidants; D002316:Cardiotonic Agents; D017392:Thiobarbituric Acid Reactive Substances; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D052279:Creatine Kinase, MB Form; D020169:Caspases; D000251:Adenosine Triphosphatases; D005978:Glutathione; D015736:Felodipine
keywords: ATPase; Cardiotoxic agents; Caspase-3; Doxorubicin; ECG; Felodipine