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The use of aliskiren as an antifibrotic drug in experimental models: A systematic review

Altarejo Marin, T. and Machado Bertassoli, B. and Alves de Siqueira de Carvalho, A. and Feder, D.

Drug Dev Res (2020) 81: 114–126

DOI: 10.1002/ddr.21610

Abstract

Aliskiren is an oral antihypertensive medication that acts by directly inhibiting renin. High levels of circulating renin and prorenin activate the pathological signaling pathway of fibrosis. This drug also reduces oxidative stress. Thus, the aim of this systematic review is to analyze experimental studies that show the actions of aliskiren on fibrosis. PubMed and LILACS databases were consulted using the keywords aliskiren and fibrosis within the period between 2005 and 2017. Fifty-three articles were analyzed. In the heart, aliskiren attenuated remodeling, hypertrophy, inflammatory cytokines, collagen deposition, and oxidative stress. In the kidneys, there was a reduction in interstitial fibrosis, the infiltration of inflammatory cells, apoptosis, proteinuria, and in the recruitment of macrophages. In diabetic models, an improvement in the albumin/creatinine relationship and in the insulin pathway in skeletal muscles was observed; aliskiren was beneficial to pancreatic function and glucose tolerance. In the liver, aliskiren reduced fibrosis, steatosis, inflammatory cytokines, and collagen deposition. In the lung and peritoneal tissues, there was a reduction in fibrosis. Many studies have reported on the beneficial effects of aliskiren on endothelial function and arterial rigidity. A reduction in fibrosis in different organs is cited by many authors, which complies with the results found in this review. However, studies diverge on the use of the drug in diabetic patients. Aliskiren has antifibrotic potential in several experimental models, interfering with the levels of fibrogenic cytokines and oxidative stress. Therefore, its use in diseases in which fibrosis plays an important pathophysiological role is suggested.

Citation

Altarejo Marin, T., Machado Bertassoli, B., Alves de Siqueira de Carvalho, A., & Feder, D. (2020). The use of aliskiren as an antifibrotic drug in experimental models: A systematic review. Drug Dev Res, 81(1), 114–126. https://doi.org/10.1002/ddr.21610 Animals, Disease Models, Animal, Humans, Fibrosis, *fibrosis, Oxidative Stress/drug effects, *aliskiren, *antifibrotic drug, *fibrogenic cytokine, *renin-angiotensin-aldosterone system, Amides/*administration & dosage/pharmacology, Anti-Inflammatory Agents/administration & dosage/pharmacology, Drug Repositioning, Endomyocardial Fibrosis/*drug therapy/immunology/pathology, Fumarates/*administration & dosage/pharmacology, Nephritis, Interstitial/*drug therapy/immunology/pathology

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