Browsing by Author "Marzuca-Nassr GN"

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Changes in Skeletal Muscle Protein Metabolism Signaling Induced by Glutamine Supplementation and Exercise.
(MDPI (Basel, Switzerland), 2023-11-07) Rodrigues Junior CF; Murata GM; Gerlinger-Romero F; Nachbar RT; Marzuca-Nassr GN; Gorjão R; Vitzel KF; Hirabara SM; Pithon-Curi TC; Curi R; Lemon PWR
AIM: To evaluate the effects of resistance exercise training (RET) and/or glutamine supplementation (GS) on signaling protein synthesis in adult rat skeletal muscles. METHODS: The following groups were studied: (1) control, no exercise (C); (2) exercise, hypertrophy resistance exercise training protocol (T); (3) no exercise, supplemented with glutamine (G); and (4) exercise and supplemented with glutamine (GT). The rats performed hypertrophic training, climbing a vertical ladder with a height of 1.1 m at an 80° incline relative to the horizontal with extra weights tied to their tails. The RET was performed three days a week for five weeks. Each training session consisted of six ladder climbs. The extra weight load was progressively increased for each animal during each training session. The G groups received daily L-glutamine by gavage (one g per kilogram of body weight per day) for five weeks. The C group received the same volume of water during the same period. The rats were euthanized, and the extensor digitorum longus (EDL) muscles from both hind limbs were removed and immediately weighed. Glutamine and glutamate concentrations were measured, and histological, signaling protein contents, and mRNA expression analyses were performed. RESULTS: Supplementation with free L-glutamine increased the glutamine concentration in the EDL muscle in the C group. The glutamate concentration was augmented in the EDL muscles from T rats. The EDL muscle mass did not change, but a significant rise was reported in the cross-sectional area (CSA) of the fibers in the three experimental groups. The levels of the phosphorylated proteins (pAkt/Akt, pp70S6K/p70S6K, p4E-BP1/4E-BP1, and pS6/S6 ratios) were significantly increased in EDL muscles of G rats, and the activation of p4E-BP1 was present in T rats. The fiber CSAs of the EDL muscles in T, G, and GT rats were increased compared to the C group. These changes were accompanied by a reduction in the 26 proteasome activity of EDL muscles from T rats. CONCLUSION: Five weeks of GS and/or RET induced muscle hypertrophy, as indicated by the increased CSAs of the EDL muscle fibers. The increase in CSA was mediated via the upregulated phosphorylation of Akt, 4E-BP1, p70S6k, and S6 in G animals and 4E-BP1 in T animals. In the EDL muscles from T animals, a decrease in proteasome activity, favoring a further increase in the CSA of the muscle fibers, was reported.
Characterization of muscle mass, strength and mobility of critically ill patients with SARS-CoV-2 pneumonia: Distribution by sex, age, days on mechanical ventilation, and muscle weakness.
(Frontiers Media S.A., 2023-02-10) Silva-Gutiérrez A; Artigas-Arias M; Alegría-Molina A; Guerra-Vega P; Navarrete P; Venegas Á; Montecinos C; Vásquez L; Moraga K; Rubilar C; Villagrán G; Parada R; Vitzel KF; Marzuca-Nassr GN; Mathur S
Objective: Quantify and categorize by sex, age, and time spent on mechanical ventilation (MV), the decline in skeletal muscle mass, strength and mobility in critically ill patients infected with SARS-CoV-2 and requiring mechanical ventilation while at intensive care unit (ICU). Design: Prospective observational study including participants recruited between June 2020 and February 2021 at Hospital Clínico Herminda Martin (HCHM), Chillán, Chile. The thickness of the quadriceps muscle was evaluated by ultrasonography (US) at intensive care unit admission and awakening. Muscle strength and mobility were assessed, respectively, through the Medical Research Council Sum Score (MRC-SS) and the Functional Status Score for the Intensive Care Unit Scale (FSS-ICU) both at awakening and at ICU discharge. Results were categorized by sex (female or male), age (<60 years old or ≥60 years old) and time spent on MV (≤10 days or >10 days). Setting: Intensive care unit in a public hospital. Participants: 132 participants aged 18 years old or above (women n = 49, 60 ± 13 years; men n = 85, 59 ± 12 years) admitted to intensive care unit with a confirmed diagnosis of severe SARS-CoV-2 and requiring MV for more than 48 h were included in the study. Patients with previous physical and or cognitive disorders were excluded. Interventions: Not applicable. Results: Muscle thickness have significantly decreased during intensive care unit stay, vastus intermedius (-11%; p = 0.025), rectus femoris (-20%; p < 0.001) and total quadriceps (-16%; p < 0.001). Muscle strength and mobility were improved at intensive care unit discharge when compared with measurements at awakening in intensive care unit (time effect, p < 0.001). Patients ≥60 years old or on MV for >10 days presented greater muscle loss, alongside with lower muscle strength and mobility. Conclusion: Critically ill patients infected with SARS-CoV-2 and requiring MV presented decreased muscle mass, strength, and mobility during their intensive care unit stay. Factors associated with muscle mass, such as age >60 years and >10 days of MV, exacerbated the critical condition and impaired recovery.
Editorial: Molecular and cellular mechanisms involved in inflammation, metabolism and oxidative stress induced by coronaviruses.
(Frontiers Media S.A., 2023-03-22) Hirabara SM; Gorjao R; Marzuca-Nassr GN; Vitzel KF; Vinolo MAR; Masi LN; Cloeckaert A
Editorial: Spotlight on aging: physiology, prevention, and management of skeletal muscle atrophy.
(Frontiers Media S.A., 2023-12-05) Marzuca-Nassr GN; Peñailillo L; Valladares-Ide D; Martinez-Huenchullan S; Curi R; Hirabara SM; Vitzel KF; D'Antona G
Endoplasmic Reticulum Stress and Autophagy Markers in Soleus Muscle Disuse-Induced Atrophy of Rats Treated with Fish Oil
(MDPI (Basel, Switzerland), 2021-07) Marzuca-Nassr GN; Kuwabara WMT; Vitzel KF; Murata GM; Torres RP; Mancini-Filho J; Alba-Loureiro TC; Curi R
Endoplasmic reticulum stress (ERS) and autophagy pathways are implicated in disuse muscle atrophy. The effects of high eicosapentaenoic (EPA) or high docosahexaenoic (DHA) fish oils on soleus muscle ERS and autophagy markers were investigated in a rat hindlimb suspension (HS) atrophy model. Adult Wistar male rats received daily by gavage supplementation (0.3 mL per 100 g b.w.) of mineral oil or high EPA or high DHA fish oils (FOs) for two weeks. Afterward, the rats were subjected to HS and the respective treatments concomitantly for an additional two-week period. After four weeks, we evaluated ERS and autophagy markers in the soleus muscle. Results were analyzed using two-way analysis of variance (ANOVA) and Bonferroni post hoc test. Gastrocnemius muscle ω-6/ω-3 fatty acids (FAs) ratio was decreased by both FOs indicating the tissue incorporation of omega-3 fatty acids. HS altered (p < 0.05) the protein content (decreasing total p38 and BiP and increasing p-JNK2/total JNK2 ratio, and caspase 3) and gene expressions (decreasing BiP and increasing IRE1 and PERK) of ERS and autophagy (decreasing Beclin and increasing LC3 and ATG14) markers in soleus. Both FOs attenuated (p < 0.05) the increase in PERK and ATG14 expressions induced by HS. Thus, both FOs could potentially attenuate ERS and autophagy in skeletal muscles undergoing atrophy.
Medium-Frequency Neuromuscular Electrical Stimulation in Critically Ill Patients Promoted Larger Functional Capacity Improvement During Recovery than Low-Frequency Neuromuscular Electrical Stimulation: Randomized Clinical Trial
(MDPI (Basel, Switzerland), 2025-07-31) Guerra-Vega P; Guzmán R; Betancourt C; Grage M; Vera C; Artigas-Arias M; Muñoz-Cofré R; Vitzel KF; Marzuca-Nassr GN; Axer H
Background/Objectives: This study aimed to compare the effects of low- and medium-frequency NMES, combined with a standard physical therapy (SPT) program, on functional capacity in critically ill patients. Methods: Fifty-four critically ill patients admitted into Intensive Care Unit (ICU) and on mechanical ventilation participated in this randomized, single-blinded, experimental study. Participants were randomly assigned to a Control group, who received a lower limb SPT program; the Low-frequency NMES group received lower limb SPT + NMES at 100 Hz; and the Medium-frequency NMES group received lower limb SPT + NMES at 100 Hz with a carrier frequency of 2500 Hz. The outcomes, encompassing functional capacity in the hospital, included muscle strength, handgrip strength, functional status, degree of independence for activities of daily living, functional and dynamic mobility, quality of life, and total days hospitalized. Results: Both NMES protocols combined with SPT improved functional capacity compared to the control group. Medium-frequency NMES provided additional benefits on dynamic balance, in the degree of independence to perform activities of daily living and quality of life (all p < 0.001) prior to hospital discharge. It also promoted larger gains on functional status prior to ICU discharge and on knee extension strength (both p < 0.05) prior to intermediate care unit discharge. Medium-frequency NMES also enhanced handgrip strength earlier than low-frequency NMES when compared to the control group. Notably, medium-frequency NMES was the only intervention associated with a significant reduction in total hospital stay duration (p < 0.05). Conclusions: Medium-frequency NMES, along with an SPT program in critically ill patients, showed greater benefits on functional capacity during recovery than low-frequency NMES. (Trial registration: This trial is registered on ClinicalTrials.gov: NCT05287919). Implications for rehabilitation: 1. Medium-frequency NMES may enhance physical functionality and quality of life in critically ill patients with ICU-acquired weakness. 2. Medium-frequency NMES can reduce the number of hospitalization days. 3. NMES combined with SPT represents a feasible and effective option for patients unable to engage in active rehabilitation during critical illness.
Molecular and cellular mechanisms involved in tissue-specific metabolic modulation by SARS-CoV-2
(Frontiers Media SA, 2022) dos Santos AAC; Rodrigues LE; Alecrim-Zeza AL; de Araújo Ferreira L; Trettel CDS; Gimenes GM; da Silva AF; Sousa-Filho CPB; Serdan TDA; Levada-Pires AC; Hatanaka E; Borges FT; de Barros MP; Cury-Boaventura MF; Bertolini GL; Cassolla P; Marzuca-Nassr GN; Vitzel KF; Pithon-Curi TC; Masi LN; Curi R; Gorjao R; Hirabara SM
Coronavirus disease 2019 (COVID-19) is triggered by the SARS-CoV-2, which is able to infect and cause dysfunction not only in lungs, but also in multiple organs, including central nervous system, skeletal muscle, kidneys, heart, liver, and intestine. Several metabolic disturbances are associated with cell damage or tissue injury, but the mechanisms involved are not yet fully elucidated. Some potential mechanisms involved in the COVID-19-induced tissue dysfunction are proposed, such as: (a) High expression and levels of proinflammatory cytokines, including TNF-α IL-6, IL-1β, INF-α and INF-β, increasing the systemic and tissue inflammatory state; (b) Induction of oxidative stress due to redox imbalance, resulting in cell injury or death induced by elevated production of reactive oxygen species; and (c) Deregulation of the renin-angiotensin-aldosterone system, exacerbating the inflammatory and oxidative stress responses. In this review, we discuss the main metabolic disturbances observed in different target tissues of SARS-CoV-2 and the potential mechanisms involved in these changes associated with the tissue dysfunction.
Skeletal muscle mass, strength, and physical performance gains are similar between healthy postmenopausal women and postmenopausal breast cancer survivors after 12 weeks of resistance exercise training.
(Springer Nature, 2024-11-23) Artigas-Arias M; Alegría-Molina A; Vidal-Seguel N; Muñoz-Cofre R; Carranza-Leiva J; Sepúlveda-Lara A; Vitzel KF; Huard N; Sapunar J; Salazar LA; Curi R; Marzuca-Nassr GN
Purpose Resistance exercise training (RET) effectively increases skeletal muscle mass and strength in healthy postmenopausal women. However, its effects on these parameters in postmenopausal breast cancer survivors are controversial or limited. Therefore, the aim of this study was to compare the effects of a 12-week progressive whole-body RET program on skeletal muscle mass, strength, and physical performance in healthy postmenopausal women versus postmenopausal women who survived breast cancer. Methods Thirteen healthy postmenopausal women (HEA, 54 ± 3 years, BMI 26.6 ± 2.7 kg·m2, n = 13) and eleven postmenopausal breast cancer survivors (BCS, 52 ± 5 years, BMI 26.8 ± 2.1 kg·m2, n = 11) participated in the study. Before and after the RET program, evaluations were performed on quadriceps muscle thickness, one-repetition maximum strength (1RM) for various exercises, grip strength, and physical performance. Results Both groups showed significant improvements in quadriceps muscle thickness (time effect, P < 0.001); 1RM strength for leg extension, leg press, chest press, horizontal row, and elbow extension (time effect, all P < 0.001); as well as handgrip strength (time effect, P = 0.035) and physical performance (time effect, all P < 0.001) after the 12-week RET program. There were no significant differences between the groups in response to RET for any of the outcomes measured. Conclusion Twelve weeks of RET significantly increases skeletal muscle mass, strength, and physical performance in postmenopausal women. No differences were observed between healthy postmenopausal women and postmenopausal breast cancer survivors. These findings point out that this study’s RET promotes skeletal muscle mass, strength, and performance gains regardless of breast cancer. Pre-Print Platform Research Square: https://doi.org/10.21203/rs.3.rs-4145715/v1; https://www.researchsquare.com/article/rs-4145715/v1 Clinical trial registration: NCT05690295.