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Introduction: Doxorubicin (DXR) is one of the most effective and widely used anthracycline antibiotics. However, its clinical application is hampered by toxic effects in many organs. Nephrotoxicity is one of the major side effects of anthracycline antibiotics. This study was designed to investigate the possible protective effects of aliskiren (a direct renin inhibitor) in DXR-induced nephrotoxicity in rats. Materials and methods: Wistar albino rats were intraperitoneally (ip) injected with DXR and renin activity, albumin, total protein, urea, creatinine levels in plasma and ultrastructural changes in podocytes were assessed. Results: Rats subjected to DXR administration had significant (p<0.01) increases in systolic blood pressure, plasma renin activity, plasma concentration of urea, creatinine and tissue malondialdehyde and significant (p<0.01) reductions in plasma concentrations of albumin, total protein and antioxidant defense (reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT)) in renal tissues. Furthermore, DXR-induced nephrotoxicity has also been characterized by broadening of podocyte foot processes, enlargement of glomerular basement membrane width and reduction in slit pore diameter. The above effects of DXR were significantly (p<0.01) prevented by aliskiren treatment. Conclusions: These findings revealed that the blockade of renin activity by aliskiren is a promising approach in the treatment of DXR-induced nephrotoxicity.

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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.

The present study was designed to test pretreatment multiple doses of irbesartan (IRB) 50 mg, aspirin (ASP) 100 mg and the combination of both drugs for 7 days on middle cerebral artery—occluded (MCAO) rats. Focal cerebral ischemia was induced by MCA occlusion for 2 hours followed by reperfusion for 22 hours. After 24 hours of ischemia, grip strength and locomotor activity tests were performed. Animals were immediately sacrificed, infarct volume was measured followed by the estimation of markers of oxidative stress in the whole brains. Locomotor activity and grip strength were improved in IRB- and ASP-treated rats. Infarct volume was reduced in both IRB and ASP pretreatment as compared with MCAO rats. An elevation of thiobarbituric acid reactive substance (TBARS) and a reduction in glutathione (GSH) and antioxidant enzymes viz. superoxide dismutase (SOD) and catalase were observed following MCAO. Pretreatment of IRB and ASP showed the reduction in TBARS, elevation in GSH, SOD and catalase levels as compared with MCAO rats. The protective effects of IRB, an angiotensin II receptor antagonist having affinity for AT1 receptor subtypes, could be due to inhibition of AT 1 receptor expression in addition to its neuroprotective and free radical scavenging properties in cerebral ischemia. Further, it may be possible that the combination of IRB and ASP may be useful as an add-on therapy and would yield beneficial effects, if administered immediately following the ischemia in reducing the severity of the neurological deficits. However, our results are preliminary, further studies with posttreatment of IRB and ASP are required to provide more firm view.