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Introduction: The nephroprotective effect of co-administration of vitamin C and losartan as prophylaxis against cisplatin-induced nephrotoxicity (CIN) was evaluated., Materials and Methods: Co-administration of vitamin C and losartan was compared with losartan (10 mg/kg), vitamin C (250 mg/kg), and placebo in 4 groups of rats with CIN. The prophylactic agents were injected daily for a period of 4 days, and on day 3, a single dose (6 mg/kg) of cisplatin was administrated. The animals were sacrificed 7 days later for pathological examination of the kidneys., Results: Cisplatin prevented the animals' weight gain. The serum levels of creatinine and blood urea nitrogen increased within the groups with CIN, but no significant difference was observed between the groups. The prophylaxis has no effect on serum osmolality, total protein, or nitrite concentrations. The kidney tissue damage was scored, and losartan provided a lower damage score than vitamin C and a combination of vitamin C and losartan., Conclusions: We concluded that co-administration of vitamin C and losartan was not more effective than the administration of vitamin C or losartan alone.

Background: Cisplatin (cis-diamminedichloroplatinum II; CDDP) is used widely as an antitumor drug in clinics, but is accompanied with renal toxicity. The present study was designed to compare the effect of losartan and vitamin E as prophylaxes against CDDP-induced nephrotoxicity., Methods: Thirty-two Wistar rats were divided into 5 groups: group 1 receiving losartan 10 mg/kg; group 2, vitamin E in almond oil 1 g/kg; group 3, combination of group 1 and 2 regimens; group 4, almond oil; and group 5, negative control group. All groups were treated for a 4-day period, but at day 3, groups 1-4 received a single dose (6 mg/kg) of CDDP. The animals were sacrificed 1 week after CDDP administration., Results: Animals' weight did not change significantly, but increasing blood urea nitrogen and malondialdehyde levels were observed statistically in all CDDP-treated animals. No detectable change was observed in nitrite level, but serum osmolality in groups 1, 2 and 4 was different from that for group 5 (p<0.05). Kidney damage scoring showed no significant difference between group 2 and the negative control group (group 2: 1.0 ± 0.24; group 5: 0.40 ± 0.10; p>0.05) but a statistically significant difference from the positive control group (p<0.05). The tubular damage score of group 1 also was not statistically significantly different from that of the negative control group., Conclusions: Although vitamin E or losartan as prophylaxes demonstrated some protective effects, the combination of losartan and vitamin E did not protect against CDDP-induced nephrotoxicity, for unknown reasons which may relate to pharmacokinetic or pharmacodynamic drug interactions.

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.