title: Aliskiren attenuates myocardial apoptosis and oxidative stress in chronic murine model of cardiomyopathy.
abstract: Doxorubicin (DXR) is one of the most effective antineoplastic agents. However, the optimal clinical use of this agent is limited because of marked cardiomyopathy and congestive heart failure. Renin angiotensin system (RAS) plays an important role in the development of cardiac hypertrophy, reperfusion injury and congestive heart failure. Aliskiren (ALK) is a direct inhibitor of renin and does not affect other systems involved in cardiovascular regulation. This study was designed to explore the possible protective effects of ALK (30 and 100 mg/kg, per oral [p.o.] respectively for 42 days) in chronic model of DXR (1.25 mg/kg, intraperitoneally (i.p.) sixteen equal cumulative doses) induced cardiomyopathy in rats. DXR treatment significantly (P<0.01) increased the activities of serum creatine kinase (CK-MB), lactate dehydrogenase (LDH), cardiomyocyte caspase-3 and catalase (CAT). ALK (100 mg/kg) treatment prevented the animals significantly (P<0.01) from rise in the above indices. Furthermore ALK (100 mg/kg) significantly restores the DXR-induced decrease in antioxidant defense, reduced glutathione (GSH) and superoxide dismutase (SOD). Transmission electron microscopic studies showed that DXR caused apoptosis in myocardium, manifested as condensation of chromatin network at the margins and rupture of nuclear membrane which was well protected by ALK (100 mg/kg) treatment. The present study indicates that ALK protected rats from DXR-induced cardiomyopathy.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi-62, India.
authors.forename: Azhar
authors.initials: A
authors.lastname: Rashikh
authors.forename: Shibli Jameel
authors.initials: SJ
authors.lastname: Ahmad
authors.forename: Krishna Kolappa
authors.initials: KK
authors.lastname: Pillai
authors.forename: Kanchan
authors.initials: K
authors.lastname: Kohli
authors.forename: Abul Kalam
authors.initials: AK
authors.lastname: Najmi
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000517:prevention & control*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D005650:Fumarates / Q000008:administration & dosage / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D004317:Doxorubicin; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren