title: Protective effect of a direct renin inhibitor in acute murine model of cardiotoxicity and nephrotoxicity.
abstract: This study aimed to investigate the possible protective effects of aliskiren against doxorubicin (DXR)-induced cardiorenal injury and to identify the mechanisms involved. Intraperitoneal administration of DXR (15 mg/kg, body weight, as a single dose) caused significant induction in the levels of angiotensin I, caspase-3, lactate dehydrogenase (LDH), lipid peroxidation malondialdehyde (MDA), urea, and creatinine. Concomitant decline in the levels of albumin and total protein in plasma, reduction in reduced glutathione (GSH), and antiperoxidative enzyme superoxide dismutase (SOD) levels followed by ultrastructural alterations in the myocardial and renal tissues were also observed. Oral administration of aliskiren (100 mg/kg, for a period of 14 days) significantly prevented all these DXR-induced adverse effects and maintained the rats near to normal status. However, telmisartan (10 mg/kg) pretreatment has shown slight protection in DXR-induced renal injury as evidenced by broadening of podocyte foot process and narrowing of slit pore diameter. The results of aliskiren were compared with telmisartan which was used as reference in this study. These results suggested that aliskiren has protective effects against acute model of DXR-induced cardiotoxicity and nephrotoxicity, implying that plasma renin activity plays a role in DXR-induced cardio-renal injury.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
authors.forename: Azhar
authors.initials: A
authors.lastname: Rashikh
authors.forename: Krishna Kolappa
authors.initials: KK
authors.lastname: Pillai
authors.forename: Abul Kalam
authors.initials: AK
authors.lastname: Najmi
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D066126:Cardiotoxicity / Q000517:prevention & control; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005650:Fumarates / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D004317:Doxorubicin; D005650:Fumarates; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren
keywords: aliskiren; cardiomyopathy; doxorubicin; lipid peroxidation; nephropathy; renin-angiotensin-aldosterone system