Title

 

Authors

A. Bitto¹, D. Altavilla¹, S. Messina², F. Polito³, N. Irrera², H. Marini³, F. Squadrito¹.

¹Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina
²Department of Neuroscience, Psychiatry and Anaesthesiology, University of Messina
³Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition University of Messina 

 

Abstract

Genistein has been reported to have pro-proliferative effects, promoting G1/S cell phase transition through the induction of cyclin D1, and anti-apoptotic properties. Apoptosis and the exhaustion of muscle regenerative capacity are implicated in Duchenne muscular dystrophy (DMD) pathogenesis and therefore relevant therapeutic targets. We tested whether genistein could have beneficial effects on functional, morphological and biochemical pattern in mdx mice. Five-week old mdx and wild type mice received for five weeks genistein (2 mg/kg i.p. daily) or vehicle. Genistein treatment 1) increased forelimb strength and strength normalized to weight; 2) reduced muscle necrosis and enhanced regeneration with an augmented number of myogenin-positive satellite cells and myonuclei; 3) increased cyclin D1 expression and 4) showed an antiapoptotic effect, modulating the expression of BAX and Bcl-2. Our results suggest  that this isoflavone might promote the regenerative spurt in mdx mice muscle promoting G1/S phase transition in muscle cell and inhibiting apoptosis. Further studies are needed to investigate the underlying mechanisms of suchencouraging results taking into account that this supplement could be easily introduced in the daily diet of patients with DMD.