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 CPtreated 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.

Angiotensin Type-1 Receptor Blockade May Not Protect Kidney against Cisplatin-Induced Nephrotoxicity in Rats

“…Inflammation, oxidative stress, and change in the renal circulation may also be induced by CDDP [4–6]. To decline CDDP-induced nephrotoxicity, recent studies have concentrated on many supplementations [7–11]. Losartan is an angiotensin type-1 receptor blocker as well as an antioxidant, which has been suggested to be nephroprotective against CDDP-induced nephrotoxicity by others [10, 11].…”

“…To decline CDDP-induced nephrotoxicity, recent studies have concentrated on many supplementations [7–11]. Losartan is an angiotensin type-1 receptor blocker as well as an antioxidant, which has been suggested to be nephroprotective against CDDP-induced nephrotoxicity by others [10, 11]. Losartan may reduce renal disease progression in patients with type 2 diabetes [12] and decrease hypertension [13] and microalbuminuria or proteinuria [14, 15].…”

“…Losartan may reduce renal disease progression in patients with type 2 diabetes [12] and decrease hypertension [13] and microalbuminuria or proteinuria [14, 15]. Several studies have presented different effects of losartan on nephrotoxicity induced by nephrotoxic compounds such as CDDP [10, 11, 16, 17]. Losartan may prevent nephrotoxicity caused by administration of single dose of CDDP in males [11, 16, 17], but it promotes renal damage in females [11].…”

Modification of paclitaxel-loaded solid lipid nanoparticles with 2-hydroxypropyl-&beta;-cyclodextrin enhances absorption and reduces nephrotoxicity associated with intravenous injection

“…Additionally, the damaged kidneys gain weight, and the serum creatinine level increases as the damage increases. [30][31][32][33][34] Therefore, the renal effects of PTX solution, PS, or PSC were examined by determining the kidney weights and serum creatinine levels. The normalized kidney weight after treatment with PTX solution was 4.87±0.35 mg/g, significantly (1.35-fold) higher than that of nontreated kidney ( Figure 5A).…”

C-Phycocyanin attenuates cisplatin-induced nephrotoxicity in mice

“…3 In another study, we observed that losartan as an angiotensin receptor blocker could attenuate cisplatin kidney toxicity in male rats, while it aggravates the cisplatin kidney injury in female rats. 4 We concluded that gender difference of cisplatin renal toxicity was related to the reninangiotensin system receptors in the kidneys. [4][5][6][7][8][9] Moreover, we recently found that vitamin C, vitamin E, or losartan have no ameliorative effects against cisplatin-kidney toxicity in presence of estrogen in ovariectomized rat model of cisplatin toxicity, 10 which is in agreement with our previous findings too.…”