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

Autor: Carmen Parisio, Carla Ghelardini, Barbara Tenci, Elena Lucarini, Alessandra Toti, Alessandra Pacini, Jacopo Junio Valerio Branca, Laura Micheli, Lorenzo Di Cesare Mannelli, Matteo Zanardelli
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Sarcopenia
Muscle Fibers
Skeletal
Cell
Fluorescent Antibody Technique
Pharmaceutical Science
Dexamethasone
Analytical Chemistry
Myoblasts
Mice
chemistry.chemical_compound
0302 clinical medicine
thioctic acid
Drug Discovery
oxidative stress
Cells
Cultured
0303 health sciences
musculoskeletal system
Myotube differentiation
Muscular Atrophy
Lipoic acid
medicine.anatomical_structure
Chemistry (miscellaneous)
Molecular Medicine
leucine
C2C12
Cell Survival
030209 endocrinology & metabolism
Caspase 3
Butyrate
macromolecular substances
Article
Cell Line
lcsh:QD241-441
03 medical and health sciences
lcsh:Organic chemistry
Valerates
medicine
Animals
Viability assay
Physical and Theoretical Chemistry
Muscle
Skeletal
030304 developmental biology
Organic Chemistry
muscle wasting
medicine.disease
Molecular biology
chemistry
myotube
human activities
Biomarkers
Zdroj: Molecules
Volume 25
Issue 9
Molecules, Vol 25, Iss 2117, p 2117 (2020)
ISSN: 1420-3049
DOI: 10.3390/molecules25092117
Popis: 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 µ
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 µ
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 µ
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.
Databáze: OpenAIRE
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