Effects of the Combination of β-Hydroxy-β-Methyl Butyrate and R(+) Lipoic Acid in a Cellular Model of Sarcopenia
Lorenzo Di Cesare Mannelli,
Laura Micheli,
Elena Lucarini,
Carmen Parisio,
Alessandra Toti,
Barbara Tenci,
Matteo Zanardelli,
Jacopo Junio Valerio Branca,
Alessandra Pacini,
Carla Ghelardini
Affiliations
Lorenzo Di Cesare Mannelli
Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence. Viale Pieraccini 6, 50139 Florence, Italy
Laura Micheli
Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence. Viale Pieraccini 6, 50139 Florence, Italy
Elena Lucarini
Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence. Viale Pieraccini 6, 50139 Florence, Italy
Carmen Parisio
Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence. Viale Pieraccini 6, 50139 Florence, Italy
Alessandra Toti
Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence. Viale Pieraccini 6, 50139 Florence, Italy
Barbara Tenci
Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence. Viale Pieraccini 6, 50139 Florence, Italy
Matteo Zanardelli
Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence. Viale Pieraccini 6, 50139 Florence, Italy
Jacopo Junio Valerio Branca
Department of Experimental and Clinical Medicine, Anatomy Section, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
Alessandra Pacini
Department of Experimental and Clinical Medicine, Anatomy Section, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
Carla Ghelardini
Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence. Viale Pieraccini 6, 50139 Florence, Italy
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 β-hydroxy-β-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 (0.01–300 µM concentration range) is evaluated in myoblasts to measure cell viability and caspase 3 activation after 24 h and 48 h; cell incubation with 1 µM 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 µM R(+)LA is combined with 1 mM HMB. Regarding myoblasts, this combination significantly reduces DEX-evoked O2− 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.
