Myocardial Fibrosis is Unaltered by Long-Term Administration of L-Arginine in Dystrophin Deficient Mdx Mice: A Histomorphometric Analysis
Cardiac failure secondary to myocardial fibrosis (MF) significantly contributes to death in Duchenne muscular dystrophy (DMD), a fatal form of muscle disease. In aging, the mdx mice, an animal model of DMD, MF is similar to that observed in humans. Nitric oxide-based therapy has been proposed to retard MF in DMD and a candidate is L-arginine (L-arg). In this study we evaluated the effects of long-term therapy with L-arg in the MF of mdx mice. Mdx mice (6 months old) were treated with L-arg in drinking water. Control mdx mice received water only. After 15 months of treatment, hearts were stained with Masson’s trichrome for analysis of MF and with hematoxilyn and eosin for analysis of inflammation and cardiomyocyte damage. We observed that MF was not affected (29.5 ±2.5% of MF area for control vs 31.4±2% for L-arginine-treated animals; P>0.05). The density of inflammatory cells was reduced (169±12 cells/mm2 in control vs 102±9 cells/mm2 in L-arg-treated; P<0.05). The present study shows that long-term administration of L-arg is not effective in retarding MF in mdx dystrophinopathy
KeywordsCardiac failure cardiac fibrosis cardiomyopathy Duchenne muscular dystrophy
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This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grants 95/6110-2, 01/00570-4 and 04/15526-9). H. S. N. and M. J. M. are recipients of fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grants 301386/07-2, 302006/09-5 and 474708/06-3). A.P.T.T. is the recipient of a CNPq fellowship.
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