Myocardial fibrosis is unaltered by long-term administration of l-arginine in dystrophin deficient mdx mice: a histomorphometric analysis

Acta Biologica Hungarica 61(2), pp. 168–174 (2010)
DOI: 10.1556/ABiol.61.2010.2.5

Myocardial fibrosis is unaltered by long-terM adMinistration of l-arginine in dystrophin deficient mDx Mice: a histoMorphoMetric analysis
Maria Julia Marques, isabel Cristina Chagas barbin, ana Paula tieMi taniguti, Daniela silva Oggian,
r. Ferretti and h. santO netO*
Departamento de Anatomia, Instituto de Biologia Celular, Fisiologia e Biofisica, universidade estadual de campinas (unicaMp), cp 6109, 13083-970, campinas, sp, brazil
(Received: May 27, 2009; accepted: July 27, 2009)
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.
Keywords: Cardiac failure – cardiac fibrosis – cardiomyopathy – Duchenne muscular dystrophy

introduction
Duchenne muscular dystrophy (DMD) is the most common X-linked disease, affecting 1 in 3,500 newborn males. It is a fatal form of muscular dystrophy caused by the absence of dystrophin, a