The role of the renin-angiotensin system in cisplatin nephrotoxicity
| Autor: | Michael P. Ryan, Patricia M. Deegan, Cearuil Nolan, Mark M. Jones, Mark A. Basinger, K. R. Hande |
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| Rok vydání: | 1995 |
| Předmět: |
Male
medicine.medical_specialty Renal function Tetrazoles Antineoplastic Agents Critical Care and Intensive Care Medicine Kidney Kidney Function Tests Losartan Nephrotoxicity Blood Urea Nitrogen Rats Sprague-Dawley Renin-Angiotensin System chemistry.chemical_compound Internal medicine medicine Animals Drug Interactions Blood urea nitrogen Cisplatin Creatinine Dose-Response Relationship Drug business.industry Angiotensin II Biphenyl Compounds Imidazoles Kidney metabolism General Medicine Rats Disease Models Animal Endocrinology chemistry Nephrology business Injections Intraperitoneal medicine.drug |
| Zdroj: | Renal failure. 17(6) |
| ISSN: | 0886-022X |
| Popis: | The role of the renin-angiotensin system (RAS) in the pathogenesis of cisplatin nephrotoxicity was evaluated in an experimental rat model using a specific, nonpeptide angiotensin II(AII) receptor blocker, losartan. Rats were treated with a single dose of losartan (at 10 mg/kg and 30 mg/kg, i.p.) or saline, 2 h prior to cisplatin administration (5 mg/kg, i.p.). Renal function was assessed 3 and 7 days after cisplatin treatment. A second group of rats received losartan (10 mg/kg, i.p.) or saline, 2 h prior to cisplatin administration (5 mg/kg, i.p.), and losartan (10 mg/kg, i.p.) or saline daily for 6 days after cisplatin treatment. Renal function was assessed on day 7. Neither high- nor low-dose losartan pretreatment prevented development of cisplatin-induced nephrotoxicity. Blood urea nitrogen (BUN) and plasma creatinine values at 7 days were similar to those of animals receiving cisplatin alone (BUN: 17.12 +/- 1.1 and 22.17 +/- 2.2 vs. 20.58 +/- 2.4 mg/dL; creatinine: 1.04 +/- 0.05 and 0.82 +/- 0.09 vs. 0.84 +/- 0.06 mg/dL). A significant reduction in creatinine clearance with cisplatin treatment was seen 3 days after therapy, which was not prevented by pretreatment with losartan (GFR in controls: 2.1 +/- 0.16 mL/min; cisplatin: 0.24 +/- 0.05; cisplatin plus low-dose losartan: 0.05 +/- 0.03 and cisplatin plus high-dose losartan: 0.37 +/- 0.05). All groups of cisplatin-treated rats displayed systemic signs of cisplatin toxicity: reduced food intake and body weight. Rats receiving chronic losartan treatment had more rapid weight gain and lower BUN and plasma creatinine levels on day 7 than rats receiving cisplatin alone (BUN: 24.0 +/- 2.64 vs. 36.4 +/- 0.91 mg/dL; p < 0.05; plasma creatinine: 0.86 +/- 0.06 vs. 1.15 +/- 0.07 mg/dL; p < 0.05). Acute blockade of the AII receptor with losartan does not alter the onset or severity of cisplatin nephrotoxicity. Chronic blockade of the AII receptor may improve the rate of recovery of renal function in cisplatin-treated rats. |
| Databáze: | OpenAIRE |
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