Protective effects of aliskiren in doxorubicin-induced acute cardiomyopathy in rats.
In this study, effect of aliskiren (ALK) on doxorubicin (DXR)-induced cardiomyopathy in rats was evaluated. ALK (50 and 100 mg/kg/day) was administered for 7 days and a single intraperitoneal injection of DXR (20 mg/kg) on day 5. The animals were sacrificed 48 h after DXR administration. DXR produced significant elevation in malondialdehyde (MDA) and significantly inhibited the activity of glutathione (GSH) in heart tissue, with a significant rise in the serum levels of lactate dehydrogenase (LDH), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and reduction in high-density lipoprotein (HDL), indicating acute cardiac toxicity. ALK pretreatment significantly reduced the MDA concentration and ameliorated the inhibition of cardiac GSH activity. ALK also significantly improved the serum levels of LDH, TC, TG, LDL and reduction in HDL in DXR-treated rats. Furthermore, histological examination of the heart sections confirmed the myocardial injury with DXR administration and the near-normal pattern with ALK pretreatment. The results provide clear evidence that the ALK pretreatment offered significant protection against DXR-induced enzymatic changes and cardiac tissue damage.
Rashikh
Azhar
A
Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, India.
Abul Kalam Najmi
Akhtar
Mohammad
M
Mahmood
Danish
D
Pillai
Krishna K
KK
Ahmad
Shibli J
SJ
D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D004317:Doxorubicin / Q000009:adverse effects*; D005650:Fumarates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000092502:Renin Inhibitors
D000577:Amides; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D005650:Fumarates; D008055:Lipids; D000092502:Renin Inhibitors; C446481:aliskiren