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.

BackgroundNephrotoxicity and hepatotoxicity are side effects of Cisplatin (CP) therapy.ObjectivesWe investigated the role of gender in CP-induced nephrotoxicity and hepatotoxicity.Materials and MethodsLow dose of CP (1 mg/kg/day; ip) was administered daily to male and female Wistar rats for 15 consecutive days. Serum creatinine (Cr), blood urea nitrogen (BUN), malondialdehyde (MDA), nitric oxide (NO) metabolite, and magnesium (Mg) levels were determined.ResultsThe percentage of weight loss and the serum levels of MDA and nitrite in male and female animals were not statistically different. However, the serum levels of BUN, Cr, Mg, and kidney MDA levels, and kidney weight and damage score were significantly greater in males than in females (P < 0.05).ConclusionsCP-induced nephrotoxicity is gender related for which the mechanisms should be determined.

Background. The nephroprotective effect of vitamins E and C or losartan against cisplatin (CP)- induced nephrotoxicity when they are accompanied by estrogen was investigated. Methods. The ovariectomized rats received estradiol valerate for two weeks. At the end of the first week, a single dose of CP (7 mg/kg, IP) was also administered, and they received placebo (group 1), vitamin E (group 2), vitamin C (group 3), or losartan (group 4) every day during the second week, and they were compared with another three control groups. Results. CP alone increased the serum levels of blood urea nitrogen (BUN), creatinine (Cr), and kidney tissue damage score (KTDS), significantly (P < 0.05), however at the presence of estradiol and CP, vitamin C, vitamin E, or losartan not only did not decrease these parameters, but also increased them significantly (P < 0.05). The serum level of superoxidase dismutase (SOD) was reduced by CP (P < 0.05), but it was increased when estradiol or estradiol plus vitamin C or losartan were added (P < 0.05). Conclusion. The particular pharmacological dose of estrogen used in this study abolish the nephroprotective effects vitamins C and E or losartan against CP-induced nephrotoxicity.

Introduction. Nephrotoxicity is one the side effect of cisplatin therapy and erythropoietin has been candidate as a nephroprotectant agent. However, its nephroprotective effect when it is accompained with estrogen has not been studied in female. Methods. 27 ovariectomized female Wistar rats divided into five groups. Groups 1 & 2 received estradiol valerate (0.5 mg/kg/week) for four weeks, and single dose of cisplatin (7 mg/kg, ip) was administrated at the end of week 3. Then the group 1 was treated with erythropoietin (100 U/kg/day), and the group 2 received vehicle during week 4. Groups 3 and 4 were treated similar to group 1 and 2, except for placebo instead estradiol valerate. Group5 (negative control) received placebo during the study. Animals were killed at the end of week 4. Results. In non-erythropoietin treated rats, cisplatin significantly increased the serum levels of blood urea nitrogen and creatinine (P < 0.05). However, these biomarkers significantly decreased by erythropoietin (P < 0.05). The weight loss, kidney weight, and kidney tissue damage score in rats treated with cisplatin but without estradiol were significantly less than the values in similar group when estradiol was present (P < 0.05). Conclusion. It seems that erythropoietin could protect the kidney against cisplatin-induced nephrotoxicity. This protective effect was not observed when estrogen was present.

Background:Cisplatin (CP) is an effective drug in cancer therapy to treat the solid tumors, but it is accompanied with nephrotoxicity. The protective effect of estrogen in cardiovascular diseases is well-documented; but its nephron-protective effect against CP-induced nephrotoxicity is not completely understood.Materials and Methods:Thirty ovarectomized Wistar rats were divided in to five groups. Groups 1-3 received different doses of estradiol valerate (0.5, 2.5 and 10 mg/kg/week) in sesame oil for 4 weeks, and at the end of week 3, a single dose of CP (7 mg/kg, intraperitoneal [IP]) was administrated. Group 4 (positive control) received the same regimen as group 1-3 without estradiol without vehicle. The negative control group (Group 5) received sesame oil during the study. The animals were sacrificed 1 week after CP injection for histopathological studies.Results:The serum level of blood urea nitrogen and creatinine, kidney tissue damage score (KTDS), kidney weight and percentage of body weight change in CP-treated groups significantly increased (P < 0.05), however, there were no significant differences detected between the estrogen-treated groups (Groups 1-3) and the positive control group (Group 4). Although, estradiol administration enhanced the serum level of nitrite, it was not affected by CP. Finally, significant correlation between KTDS and kidney weight was detected (r2 = 0.63, P < 0.01).Conclusion:Estrogen is not nephron-protective against CP-induced nephrotoxicity. Moreover, it seems that the mechanism may be related to estrogen-induced oxidative stress in the kidney, which may promote the nephrotoxicity.