Effect of smoking on cyclosporin A-induced chronic nephrotoxicity in rats

• Grant number: 07/05837-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): March 01, 2008
• Effective date (End): February 28, 2009
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Emmanuel de Almeida Burdmann
• Grantee: Rafael Paula e Silva Felici de Souza
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

Cyclosporine A (CSA) is a potent immunosuppressive drug that improved the survival rate of the transplanted tissue and the patients quality of life. However, it causes important side effects, including acute and chronic nephrotoxicity. Frequently, the transplant recipient presents risk factors for renal injury such as age, mellitus diabetes, hypertension, dyslipidemia and cigarette smoking. Out of those, cigarette smoking is associated with the progression of chronic kidney disease. Other studies have shown that nicotine causes important renal and systemic modifications like elevated blood pressure and renal hemodynamic and morphological changes. Since CSA causes functional and structural kidney damage, and cigarette also produces or worse renal injury, it is possible that the association of them (CSA and cigarette) will potentiate the renal injury effects of both. The purpose of the present study is to evaluate the action of cigarette smoking on the CSA-induced chronic nephrotoxicity in rats. It will be used male Munich-Wistar rats, weighting around 200g, divided in 3 groups: Control (vehicle), CSA (2.5 mg/28 days) and CSA + smoking (2.5 mg/28 days + 16 weeks at the smoking box). At the end of the treatment the following parameters will be analyzed: sodium, potassium, blood and urine creatinine, urine albumin, glomerular filtration rate using inulin depuration and renal histology.