Effects of the Combination of β-Hydroxy-β-Methyl Butyrate and R(+) Lipoic Acid in a Cellular Model of Sarcopenia

Sarcopenia is a clinical problem associated with several pathological and non-pathological conditions. The aim of the present research is the evaluation of the pharmacological profile of the leucine metabolite &beta
hydroxy-&beta
methyl butyrate (HMB) associated with the natural R(+) stereoisomer of lipoic acid (R(+)LA) in a cellular model of muscle wasting. The C2C12 cell line is used as myoblasts or is differentiated in myotubes, sarcopenia is induced by dexamethasone (DEX). A Bonferroni significant difference procedure is used for a post hoc comparison. DEX toxicity (0.01&ndash
300 &micro
M concentration range) is evaluated in myoblasts to measure cell viability and caspase 3 activation after 24 h and 48 h
cell incubation with 1 &micro
M DEX for 48 h is chosen as optimal treatment for decreasing cell viability and increasing caspase 3 activity. R(+)LA or HMB significantly prevents DEX-induced cell mortality
the efficacy is improved when 100 &micro
M R(+)LA is combined with 1 mM HMB. Regarding myoblasts, this combination significantly reduces DEX-evoked O2&minus
production and protein oxidative damage. During the early phase of myotube formation, the mixture preserves the number of myogenin-positive cells, whereas it completely prevents the DEX-dependent damage in a later phase of myotube differentiation (7 days), as evaluated by cell diameter and percentage of multinucleated cells. R(+)LA in association with HMB is suggested for sarcopenia therapy.