Hydroxy group requirement for halofuginone-dependent inhibition of muscle fibrosis and improvement of histopathology in the mdx mouse model for Duchenne muscular dystrophy.

Hydroxy group requirement for halofuginone-dependent inhibition of muscle fibrosis and improvement of histopathology in the mdx mouse model for Duchenne muscular dystrophy. Histol Histopathol. 2019 Jan 10;:18083 Authors: Wellner G, Mordechay S, Evans P, Genin O, Pines M, Halevy O Abstract In Duchenne muscular dystrophy (DMD), the progressive loss of muscle and its ability to function is associated with significant fibrosis, representing the major disease complication in patients. Halofuginone, a halogenated analog of the naturally occurring febrifugine, has been shown to prevent fibrosis in various animal models, including those of muscular dystrophies. Here, two optically active enantiomers of deoxyhalofuginone-a halofuginone analogue in which the hydroxy group in position 3 was removed from the piperidinyl entity-were evaluated with respect to their effect on muscle histopathology in mdx mice. Male mdx mice were treated with either deoxyhalofuginone (as single enantiomers or in racemic form), or halofuginone, for 10 weeks, starting at the age of 4 weeks. Halofuginone caused a significant reduction in total collagen content, degenerative areas, as well as in utrophin and phosphorylated-Smad3 levels in the mdx diaphragms. However, neither the deoxyhalofuginone enantiomers, nor its racemic form had any effect on these parameters. A positive effect of the deoxyhalofuginone (+)-enantiomer was observed on myofiber diameters; however, it ...
Source: Histology and Histopathology - Category: Cytology Tags: Histol Histopathol Source Type: research