Rashikh Azhar, Pillai Krishna Kolappa, Najmi Abul Kalam
Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
Fundam Clin Pharmacol. 2014 Oct;28(5):489-500. doi: 10.1111/fcp.12054. Epub 2013 Nov 27.
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.
本研究旨在探讨阿利吉仑对阿霉素（DXR）诱导的心肾损伤的可能保护作用，并确定其中涉及的机制。腹腔注射DXR（15毫克/千克体重，单次剂量）导致血管紧张素I、半胱天冬酶-3、乳酸脱氢酶（LDH）、脂质过氧化丙二醛（MDA）、尿素和肌酐水平显著升高。还观察到血浆中白蛋白和总蛋白水平随之下降、还原型谷胱甘肽（GSH）减少以及抗过氧化酶超氧化物歧化酶（SOD）水平降低，随后心肌和肾组织出现超微结构改变。口服阿利吉仑（100毫克/千克，持续14天）显著预防了所有这些DXR诱导的不良反应，并使大鼠维持在接近正常的状态。然而，替米沙坦（10毫克/千克）预处理在DXR诱导的肾损伤中显示出轻微保护作用，表现为足细胞足突增宽和裂孔直径变窄。将阿利吉仑的结果与本研究中用作对照的替米沙坦进行了比较。这些结果表明，阿利吉仑对DXR诱导的心脏毒性和肾毒性急性模型具有保护作用，这意味着血浆肾素活性在DXR诱导的心肾损伤中起作用。
