Beneficial effects of pioglitazone against cardiovascular injury are enhanced by combination with aliskiren in a rat model of diabetic nephropathy

The Journal of Pharmacy and Pharmacology
Rania A ElrashidyHoda E Mohamed

Abstract

Aliskiren is the first in a new class of orally active direct renin inhibitors, approved for the treatment of hypertension. However, the efficacy of aliskiren in diabetic cardiovascular complications remains to be defined. This study aimed to test the hypothesis that aliskiren may enhance the beneficial effects of pioglitazone against cardiovascular injury associated with diabetic nephropathy. Diabetic nephropathy was induced in rats by unilateral nephrectomy followed by streptozotocin injection. Diabetic nephropathic rats were orally given vehicle, pioglitazone, aliskiren, or combined pioglitazone and aliskiren for four weeks to compare their effects on cardiovascular injury, particularly myocardial fibrosis. Pioglitazone treatment significantly attenuated cardiac lipid peroxidation, oxidative injury and myocardial fibrosis in diabetic nephropathic rats. This was associated with up-regulation of transforming growth factor-β1 and matrix metalloproteinase-2 genes, along with down-regulation of tissue inhibitor of metalloproteinase-2 gene in cardiac tissue. The combination of aliskiren with pioglitazone exerted greater beneficial effect than monotherapy with either drug, on all the aforementioned parameters. Our findings suggeste...Continue Reading

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Oct 13, 2019·Drug Development Research·Thainá Altarejo MarinDavid Feder
Apr 26, 2017·Frontiers in Endocrinology·Paras K MishraSushil K Mahata
Nov 17, 2020·Frontiers in Cardiovascular Medicine·Namrita KaurWei Liu

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