Submitted: 17 Aug 2020
Accepted: 06 Dec 2020
ePublished: 13 Jan 2021
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J Nephropharmacol. 2022;11(1): e10.
doi: 10.34172/npj.2022.10

Scopus ID: 85119617293
  Abstract View: 494
  PDF Download: 150


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

Sayyedehnikta Kasaei 1 ORCID logo, Zahra Pezeshki 1 ORCID logo, Farzaneh Karimi 1 ORCID logo, Zahra Lak 1 ORCID logo, Samira Choopani 1 ORCID logo, Ardeshir Talebi 1,2 ORCID logo, Mehdi Nematbakhsh 1,3,4* ORCID logo

1 Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Clinical Pathology, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran
4 Isfahan MN Institute of Basic and Applied Sciences Research, Isfahan, Iran
*Corresponding Author: *Corresponding author: Prof. Mehdi Nematbakhsh, Ph.D, Email: nematbakhsh@med.mui.ac.ir, , Email: nematbakhsh@gmail.com


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.

Implication for health policy/practice/research/medical education:

Prescribing losartan in females may have the opposite effect to protect the kidney against cisplatin-induced nephrotoxicity.

Please cite this paper as: Kasaei S, Pezeshki Z, Karimi F, Lak Z, Choopani S, Talebi A, Nematbakhsh M. Angiotensin 1-7 and losartan worsen the cisplatin induced nephrotoxicity in female rats. J Nephropharmacol. 2022;11(1):e10. DOI: 10.34172/ npj.2022.10.

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