The Role of Angiotensin II Receptor 1 (AT1) Blockade in Cisplatin-Induced Nephrotoxicity in Rats: Gender-Related Differences

Abstract

It is documented that chronic renal diseases are gender related. The protective role of angiotensin II receptor 1 (AT1) blocker losartan against cisplatin (CP)-induced nephrotoxicity was reported in males, but the role of gender is not well known. Six groups of Wistar rats were studied. Rats were divided into two groups of males and females to receive losartan for 9 days plus a single dose of CP (7 mg/kg) at day 3. Two positive control groups of males and females received the same regimen, except that they received saline instead of losartan. The negative control groups received saline instead of CP at day 3 and also saline instead of losartan. The blood samples were obtained, and the kidneys underwent histopathological investigations. All the CP-treated animals lost weight, but losartan promoted weight loss in females (p < 0.05). Coadministration of losartan and CP in females, but not in males, significantly increased the serum levels of blood urea nitrogen and creatinine when compared with the negative and positive control groups (p < 0.05). No significant differences were observed in serum levels of total proteins, magnesium, and nitrite between the groups. Administration of CP increased the kidney tissue damage score (KTDS) and normalized kidney weight (p < 0.05). However, in the presence of AT1 blockade, the KTDS (nonsignificantly) and normalized kidney weight (significantly, p < 0.05) increased in the CP-treated females. Such an observation was not seen in males. Losartan may prevent CP-induced nephrotoxicity in males, but it promotes the CP-induced damage in females, which may be related to the renin–angiotensin system receptors in the kidneys.

• cisplatin
• nephrotoxicity
• gender
• angiotensin II
• AT1
• rat

ACKNOWLEDGMENT

This research was supported by Isfahan University of Medical Sciences.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.