P.321 - Ultrasonography evaluation of long-term taurine effects on cardiac and skeletal muscles of mdx mice

Abstract

Taurine (Tau) is the most abundant free amino acid in heart and skeletal muscle. In these tissues Tau is involved in normal contractile function by regulating the calcium homeostasis and the calcium sensitivity of the contractile proteins. Preclinical studies in mdx mice disclosed promising effects of Tau as a countermeasure for the early alterations of skeletal muscle in Duchenne muscular dystrophy (DMD). DMD is a rare disease caused by the absence of sub-sarcolemmal protein dystrophin, progressively leading to skeletal muscle wasting and heart failure via altered calcium homeostasis abnormal inflammation and profibrotic signaling. We presently focused on the potential effectiveness of Tau supplementation on later cardiac muscle dysfunction in DMD, since this has never been investigated up to now. Tau was orally administered (1g/kg/daily) in male wild type (WT) and mdx mice at an initial age of 6 months. The treatment duration was 6 months. Tau effects were tested on WT and mdx mice by measuring body mass, in vivo force and resistance to treadmill exercise. In parallel, by using an UBM system (Vevo 2100; VisualSonics, Canada), ultrasound evaluation of the left ventricular function and hindlimb volume (V) and percentage of vascularization (%V) were also performed. Our results showed a significant reduction of stroke volume (SV; -30%), ejection fraction (EF; -18.4%) and fractional shortening (FS; -23%) in 12 months old untreated mdx mice with respect to the age-matched untreated WT. Interestingly, Tau treatment significantly and selectively counteracted the alterations of SV, EF and SF in mdx mice as the values were similar to those of untreated WT mice. No significant effects were observed on the V and %V of hindlimb skeletal muscle as well as on the other functional parameters in response to Tau. This study provide the new evidence that long term Tau supplementation could be an effective specific countermeasure for DMD cardiomyopathy (DPP-NL and PRIN-MIUR).