Title:N-Acetyl Cysteine Attenuates the Sarcopenia and Muscle Apoptosis Induced by Chronic Liver Disease
VOLUME: 20 ISSUE: 1
Author(s):Johanna Abrigo, Tabita Marín, Francisco Aguirre, Franco Tacchi, Cristian Vilos, Felipe Simon, Marco Arrese, Daniel Cabrera and Claudio Cabello-Verrugio*
Affiliation:Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago, Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago, Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago, Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago, Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago, Millennium Institute on Immunology and Immunotherapy, Santiago, Departamento de Gastroenterologia, Facultad de Medicina. Pontificia Universidad Catolica de Chile, Santiago, Departamento de Gastroenterologia, Facultad de Medicina. Pontificia Universidad Catolica de Chile, Santiago, Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago
Keywords:Sarcopenia, chronic liver disease, hepatotoxin, UPP oxidative stress, apoptosis.
Abstract:
Background: Sarcopenia is characterized by the loss of muscle mass and
strength (muscle atrophy) because of aging or chronic diseases, such as chronic liver
disease (CLD). Different mechanisms are involved in skeletal muscle atrophy, including
decreased muscle fibre diameter and myosin heavy chain levels and increased
ubiquitin–proteasome pathway activity, oxidative stress and myonuclear apoptosis. We
recently found that all these mechanisms, except myonuclear apoptosis, which was not
evaluated in the previous study, were involved in muscle atrophy associated with
hepatotoxin 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced CLD.
Objective: In the present study, we evaluated the involvement of myonuclear apoptosis
in CLD-associated sarcopenia and the effect of N-acetyl cysteine (NAC) treatment on
muscle strength and apoptosis, using a DDC-supplemented diet-fed mouse model.
Methods: Four-month-old male C57BL6 mice were fed with a standard or DDCsupplemented
diet for six weeks in the absence or presence of NAC treatment.
Results: Our results showed that NAC attenuated the decrease in muscle fibre diameter
and muscle strength associated with CLD-induced muscle wasting in gastrocnemius
(GA) muscle of DDC-supplemented diet-fed mice. In addition, in GA muscle of the mice
fed with DDC-supplemented diet-induced CLD showed increased myonuclear apoptosis
compared with the GA muscle of the control diet-fed mice, as evidenced by increased
apoptotic nuclei number, caspase-8 and caspase-9 expression, enzymatic activity of
caspase-3 and BAX/BCL-2 ratio. NAC treatment inhibited all the mechanisms
associated with myonuclear apoptosis in the GA muscle.
Conclusion: To our knowledge, this is the first study which reports the redox regulation
of muscle strength and myonuclear apoptosis in CLD-induced sarcopenia.
