Full text
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| Author(s): |
Camile Alba Pereira
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2007-08-29 |
| Examining board members: |
Irene de Lourdes Noronha;
Mirian Aparecida Boim;
Marilda Mazzali
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| Advisor: | Irene de Lourdes Noronha |
| Abstract | |
Considering it importance of the mechanism of fibrosis in the chronic progressive renal disease, the present project aimed at to study the effect of pirfenidone, potentially antifibrotic drug, in the renal injury in experimental model of progressive renal disease. The experimental model of progressive renal disease was used, through the chronic inhibition of the synthesis of nitric oxide. The induction of the renal disease was made using male Wistar rats that had received L-NAME (200 mg/L in the water of the water through) and high salt diet (3.2% Na+) during 30 days. After the period of treatment (30 days) the degree of renal injury measured by the albuminuria and serum creatinine, and the interstitial degree of glomerulosclerosis and fibrosis was evaluated. The effect of pirfenidone on metaloproteinases MMP2 e MMP9 was investigaed by zymography. The effect of pirfenidone in the local of inflammation was also analyzed by evaluating of the cellular components (macrophages, lymphocytes and myofibroblasts) and the analysis of the proliferative activity (PCNA), by means of immunohistochemistry. Besides analyzing the isolated effect of pirfenidone in the experimental chronic model of progressive renal disease, the present project analyzed the effect of the association of pirfenidone to losartan, mycophenolate mofetil (MMF) and hidralazine, aiming at the effective blockade of the progression of the renal disease. The results demonstrated that in experimental chronic progressive renal the monotherapy with pirfenidona presents an important renoprotector effect. The association of this drug, with antifibrotic effect, to losartan in, MMF and hidralazine presented a marked rennoprotector effect, demonstrating that the association of drugs that act in different mechanisms, can represent an important alternative of treatment for the progression of the renal disease (AU) | |