Angiotensin 1-7 and losartan worsen the cisplatin induced nephrotoxicity in female rats

Sayyedehnikta Kasaei,Farzaneh Karimi,Mehdi Nematbakhsh,Ardeshir Talebi,Samira Choopani,Zahra Lak,Zahra Pezeshki

doi:10.34172/npj.2022.10

Sayyedehnikta Kasaei, Farzaneh Karimi + Show 5 more

Open Access

https://doi.org/10.34172/npj.2022.10

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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.

Highlights

Cisplatin (CP) is an anti-cancer drug with the most common side effects of nephrotoxicity
CP may affect renin angiotensin system (RAS) components, and it is reported that angiotensin II type 1 receptor (AT1R) antagonist has a protective role against CP induced nephrotoxicity by increasing glomerular filtration rate (GFR) and renal blood flow (RBF) [5,6,7,8]
The administration of CP increased the serum levels of blood urea nitrogen (BUN) and Cr insignificantly (Figure 1). These markers were increased (P < 0.05) when losartan, angiotensin 1-7 (Ang1-7) or a combination of Ang1-7 and A779 were accompanied by CP (Figure 1)

Summary

Introduction

Cisplatin (CP) is an anti-cancer drug with the most common side effects of nephrotoxicity. An angiotensin II type 1 receptor (AT1R) antagonist and angiotensin 1-7 (Ang1-7) protects the kidney against CP administration in males the activity of the renin angiotensin system (RAS) and the incidence of CP induced nephrotoxicity are gender related. Conclusion: The AT1R and Mas receptor (MasR) antagonists and Ang 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. Losartan as a well-known antihypertensive drug is widely used in clinical settings to control blood pressure It is an antagonized angiotensin II (AngII) type 1 receptor (AT1R), and AngII, the most important active component of renin angiotensin system (RAS) exerts its vasodepressor action via AT1R. Ang potentially may increase RBF [9]

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