L-arginine administration : the effect on myocardial fibrosis and increase of the carcinogenesis in mice mdx / Administração de L-arginina : efeitos sobre a fibrose miocardica e aumento da carcinogenese em camundongos mdx

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

The Duchenne Muscle Dystrophy (DMD) is a myopathy characterized by dystrophin absence, which is a structural protein of the plasma membrane. The dystrophin absence leads to functional alterations followed by necrosis in the skeletal and cardiac muscle fiber. As the patients grow older, about 40% of them develop cardiomyopathy due to progressive myocardial fibrosis (MF), and eventually die because of this. Therefore, a treatment that avoids the MF progression is very important to DMD patients. The mouse mdx, animal model of dystrophy, also presents progressive FM and thus, has been used as an experimental model for cardiomyopathy in DMD. The MF in mice mdx has been partially attributed to the deficiency of nitric oxide. This way, therapies based on the exogenous administration of nitric oxide have been quoted and the L-arginine, which is a substrate of the synthase nitric, has been revealed to be a strong candidate to these therapies. The aim of this current project is evaluating the effect of long-term administration of L-arginine on the progression of MF in mice mdx. The animals were treated with L-arginine for 60 weeks. The hearts were taken out and prepared for histomorphometric evaluation of the myocardial fibrosis through the colouring with Masson`s trichrome. Slides stained with hematoxilin and eosin (H&E) were used for histological observation and quantification of the density of inflamatory cells. Hearts of mice mdx at the same age of those ones treated with L-arginine were used as control. Our results show that the average area of MF in mice which received L-arginine wasn`t different (p>0,05) from the area of the control group (29,5 ± 2,5% for the control vs 31,4 ± 2% for the L-arginine). On the other hand, the density of inflamatory cells was significantly smaller in mice which received L-arginine compared to the control (169.3 ± 6.7 cells/mm² in the control vs 102 ± 6 cells/mm² in L-arginine). Based on this, we can conclude that the long-term administration of L-arginine is not enough to prevent the MF, suggesting that the use of L-arginine may not be effective to prevent the MF in DMD. During the research achievement, we could verify that the L-arginine administration increases the already known susceptibility of mice mdx of developing tumors. About 40% of the mice mdx which received L-arginine for a long time presented tumors whose histopathological analysis, including the MyoD expression, reveals them to be rhabdomyosarcomas. A further analysis reveals that most of them is the embrionic kind and one is the alveolar kind. These results are important since this protocol can be used to induce this kind of cancer and consequently serve as an experimental model for it.

ASSUNTO(S)

fibrose endomiocardica distrofia muscular de duchenne arginine mdx mice endomyocardial fibrosis camundongo mdx miocardio - doenças arginina duchenne muscular dystrophy miocardium diseases

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