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/mm 2 in control vs 102 +/- 9 cells/mm 2 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.
Universidade Estadual de Campinas (UNICAMP) Departamento de Anatomia, Instituto de Biologia Celular, Fisiologia e Biofisica CP 6109 13083-970 Campinas, SP Brazil.
Maria Julia
MJ
Marques
Isabel Cristina Chagas
IC
Barbin
Ana Paula Tiemi
AP
Taniguti
Daniela Silva
DS
Oggian
R
R
Ferretti
H
H
Santo Neto
D000818:Animals; D001120:Arginine / Q000378:metabolism; D009202:Cardiomyopathies / Q000473:pathology; D016189:Dystrophin / Q000235:genetics / Q000502:physiology*; D005355:Fibrosis / Q000473:pathology*; D007249:Inflammation; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D009132:Muscles / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D013997:Time Factors
D016189:Dystrophin; D009569:Nitric Oxide; D001120:Arginine