Angiotensin 1-7 and Losartan Worsen the Cisplatin Induced Nephrotoxicity in Female Rats Publisher



Kasaei S¹ ; Pezeshki Z¹ ; Karimi F¹ ; Lak Z¹ ; Choopani S¹ ; Talebi A^{1, 2} ; Nematbakhsh M^{1, 3, 4}
Source: Journal of Nephropharmacology Published:2022

Abstract

Introduction: Cisplatin (CP) is an anti-cancer drug with the most common side effects of nephrotoxicity. Losartan, an angiotensin II type 1 receptor (AT1R) antagonist and angiotensin 1-7 (Ang1-7) protects the kidney against CP administration in males Moreover, the activity of the renin angiotensin system (RAS) and the incidence of CP induced nephrotoxicity are gender related. Objectives: The role of Ang1-7 and losartan against CP induced nephrotoxicity in female rats was examined. Methods: Thirty-two female Wistar rats in five experimental groups were treated with vehicle, single dose of CP (7.5 mg/kg), CP+losartan (10 ), CP+Ang1-7 (30 µg/kg/d) or CP+Ang1-7+A779 (Mas receptor antagonist, 100 µg/kg/d). The biochemical and histology measurements were conducted one week later. Results: The levels of serum creatinine (Cr) and blood urea nitrogen (BUN) in serum increased insignificantly by CP alone administration. However co-treatment of CP with losartan, Ang1-7, or Ang1-7 plus A779 showed an increase of the serum levels of BUN and Cr, and kidney tissue damage score (KTDS) (P < 0.05) when compared with control groups. Conclusion: The AT1R and Mas receptor (MasR) antagonists and Ang1-7 administration promote the CP induced damage of kidney in female rats, and special attention is needed during CP therapy in hypertensive patients who are treating with anti-hypertensive drug of losartan. © 2022 The Author(s); Published by Society of Diabetic Nephropathy Prevention.