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

Autor: Di Cesare Mannelli L; Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy., Micheli L; Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy., Lucarini E; Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy., Parisio C; Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy., Toti A; Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy., Tenci B; Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy., Zanardelli M; Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy., Branca JJV; Department of Experimental and Clinical Medicine, Anatomy Section, University of Florence, Largo Brambilla 3, 50134 Florence, Italy., Pacini A; Department of Experimental and Clinical Medicine, Anatomy Section, University of Florence, Largo Brambilla 3, 50134 Florence, Italy., Ghelardini C; Department of Neurosciences, Psychology, Drug Research and Child Health-Neurofarba-Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2020 Apr 30; Vol. 25 (9). Date of Electronic Publication: 2020 Apr 30.
DOI: 10.3390/molecules25092117
Abstrakt: : 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 O 2 - 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.
Competing Interests: The authors declare no conflict of interest
Databáze: MEDLINE
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