RESUMEN

Zinc plays a crucial role in cell structure and functionality. Neurodegenerative Duchenne muscular dystrophy (DMD) alters muscle membrane structure, leading to a loss of muscle mass and strength. The objective of this study was to evaluate the changes in phase angle (PA) and bioelectrical impedance vector analysis (BIVA) results in patients with DMD after oral zinc supplementation. This clinical trial included 33 boys aged 5.6 to 24.5 years diagnosed with DMD. They were divided into three groups according to age (G1, G2, and G3) and supplemented with oral zinc. The mean serum zinc concentration was 74 µg/dL, and 29% of patients had concentrations below the reference value. The baseline values (mean (standard deviation)) of the bioelectrical impedance parameters PA, resistance (R), and reactance (Xc) were 2.59° (0.84°), 924.36 (212.31) Ω, and 39.64 (8.41) Ω, respectively. An increase in R and a decrease in PA and lean mass proportional to age were observed, along with a negative correlation (r = -0.614; p < 0.001) between age and PA. The average cell mass in G1 was greater than that in G3 (p = 0.012). There were no significant differences in serum zinc levels or bioelectrical impedance parameters before and after zinc supplementation. We conclude that this population is at risk of zinc deficiency and the proposed dosage of zinc supplementation was not sufficient to alter serum zinc levels, PA and BIVA results.

Asunto(s)

Suplementos Dietéticos , Impedancia Eléctrica , Distrofia Muscular de Duchenne , Zinc , Humanos , Distrofia Muscular de Duchenne/tratamiento farmacológico , Zinc/administración & dosificación , Zinc/sangre , Zinc/deficiencia , Masculino , Adolescente , Niño , Adulto Joven , Preescolar , Composición Corporal/efectos de los fármacos , Administración Oral , Músculo Esquelético/efectos de los fármacos

RESUMEN

BACKGROUND/OBJECTIVES: The oral administration of hydrolyzed collagen peptides is a scientifically validated intervention for enhancing skeletal muscle health and performance. This integrative review consolidates the evidence supporting the use of low molecular weight collagen peptides (2000-3500 daltons) for their superior bioavailability and absorption. Our objective was to review the effects of collagen peptide or hydrolyzed collagen supplementation on muscle damage, recovery, and construction related to physical exercise. METHODS: A bibliographic search was conducted in major English-language databases, including PubMed/Medline, using terms like "Peptides Collagen and Damage" and "collagen peptides AND Soreness Muscle". This review followed PRISMA guidelines, with bias risk assessed via the PEDro scale. The inclusion criteria were (a) randomized clinical trials, (b) randomized studies in humans with a control or placebo group, (c) studies assessing muscle damage or delayed onset muscle soreness via physiological markers or strength performance tests, and (d) studies using hydrolyzed collagen or collagen peptides. RESULTS: Initially, 752 articles were identified. After applying the inclusion and exclusion criteria, including duplicate removal, eight articles with 286 participants were included. Of these, 130 participants received collagen peptide supplementation, while 171 received a placebo or control. CONCLUSION: This integrative review supports the potential of collagen peptide supplementation to mitigate muscle stress from acute strenuous resistance training. However, due to the methodological heterogeneity among the studies, further clinical trials are needed to clarify the mechanisms underlying muscle improvement with collagen supplementation.

Asunto(s)

Colágeno , Suplementos Dietéticos , Músculo Esquelético , Mialgia , Humanos , Músculo Esquelético/efectos de los fármacos , Mialgia/tratamiento farmacológico , Péptidos/farmacología , Péptidos/administración & dosificación , Entrenamiento de Fuerza , Fatiga Muscular/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Fuerza Muscular/efectos de los fármacos , Masculino , Adulto , Femenino , Ejercicio Físico

RESUMEN

Soft tissue engineering and regenerative medicine aim to address the intricate relationship between tissue architecture and biomechanical performance. The traditional technique used to analyze muscular architectures is histology. However, optical coherence tomography is a novel non-destructive, non-invasive imaging tool that provides real-time, high-resolution visualization of tissue microstructure, making it applicable to soft tissues. High-quality images, minimized light scattering, and different clearing agents, such as propylene glycol and iodixanol, have been employed. A stress-relaxation test was performed to characterize the effects of clearing agents on rat extensor digitorum longus and soleus muscles. Additionally, muscle fiber structure images obtained using optical correlation tomography were compared with histological images to corroborate the high precision of the optical method. The results showed that iodixanol is a promising clearing agent for characterizing muscles as it provides good quality images and a satisfactory reversibility process with no permanent damage to the extracellular matrix or muscle fiber structure of the tissue.

Asunto(s)

Músculo Esquelético , Propilenglicol , Tomografía de Coherencia Óptica , Ácidos Triyodobenzoicos , Animales , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/diagnóstico por imagen , Ácidos Triyodobenzoicos/farmacología , Ácidos Triyodobenzoicos/química , Ácidos Triyodobenzoicos/administración & dosificación , Propilenglicol/química , Propilenglicol/farmacología , Ratas , Masculino , Ratas Sprague-Dawley

RESUMEN

BACKGROUND: This study examines whether creatine supplementation combined with strength training mitigates muscle mass loss in women during early rehabilitation post-bariatric surgery, as its effectiveness remains untested in this context. METHODS: Fifteen women (37.8 ± 9.6 years; BMI, 38.8 ± 5.6 kg/m2) completed the intervention (creatine group = 7; placebo group = 8). Both groups followed a strength training program three times a week for 8 weeks. The dosage for both the creatine and placebo was 8 g prior to each exercise session. Body weight, skeletal muscle mass, fat mass, handgrip strength, and physical activity levels were measured before and after the intervention. RESULTS: The creatine group showed a reduction of 9.5 ± 1.5 kg in body weight, with a 0.72 ± 0.6 kg decrease in muscle mass and an 8.64 ± 1.2 kg reduction in fat mass. The placebo group had a reduction of 9.6 ± 3.5 kg in body weight, with a 0.6 ± 1.2 kg decrease in muscle mass and an 8.88 ± 3.2 kg reduction in fat mass, without significant differences between groups (p > 0.05). CONCLUSION: The pre-session strength exercise training creatine supplementation is not superior to placebo regarding body weight and fat mass losses and the attenuation of muscle mass loss during the first weeks of rehabilitation following bariatric surgery.

Asunto(s)

Cirugía Bariátrica , Creatina , Suplementos Dietéticos , Músculo Esquelético , Entrenamiento de Fuerza , Humanos , Femenino , Creatina/administración & dosificación , Proyectos Piloto , Adulto , Entrenamiento de Fuerza/métodos , Músculo Esquelético/efectos de los fármacos , Pérdida de Peso , Obesidad Mórbida/cirugía , Fuerza de la Mano , Persona de Mediana Edad , Fuerza Muscular/fisiología , Fuerza Muscular/efectos de los fármacos

RESUMEN

OBJECTIVE: To identify whether there is an association between body composition phenotypes and toxicity to chemoradiotherapy in women with cervical cancer. METHODS: This is a prospective cohort study that included 330 adult patients with cervical cancer treated with chemoradiotherapy. Computed tomography images were used to assess skeletal muscle index (SMI) and radiodensity (SMD), total adipose tissue index, and visceral adipose tissue index. Chemoradiotherapy toxicity was assessed weekly, and toxicity-induced modification of treatment (TIMT) was considered as any severe adverse event resulting in treatment interruption, delay, or dose reduction. RESULTS: Approximately 45% of the patients presented at least one unfavorable body composition parameter (lower SMI, lower SMD, higher total adipose tissue index, or higher visceral adipose tissue index), 23% had two conditions, and 3% had three conditions. The incidence of toxicity ≥ grade 3 and TIMT was 55% and 30%, respectively. For adverse events ≥ grade 3, lower SMI was the determining factor for worse outcomes when evaluated alone or combined with lower SMD and normal adiposity. All body composition phenotypes were associated with TIMT, increasing the risk when both conditions were present. CONCLUSIONS: Lower SMI was an independent factor for the higher number of adverse events, as it remained a risk factor when analyzed in isolation or in association with adipose tissue. Women with excess adipose tissue associated with lower muscle mass had a risk approximately 4 times higher of delaying or interrupting chemoradiotherapy. Furthermore, for the sum of unfavorable conditions, there was a progressive increase in the risk of TIMT.

Asunto(s)

Composición Corporal , Quimioradioterapia , Fenotipo , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Persona de Mediana Edad , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Estudios Prospectivos , Adulto , Grasa Intraabdominal/diagnóstico por imagen , Anciano , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/efectos de la radiación , Tomografía Computarizada por Rayos X/métodos , Factores de Riesgo

RESUMEN

This study aimed to investigate the effects of caffeine ingestion by chewing gum (GUMCAF) combined with priming exercise on pulmonary oxygen uptake (V˙O2) and near-infrared spectroscopy-derived muscle oxygen extraction (HHb + Mb) kinetics during cycling performed in a severe-intensity domain. Fifteen trained cyclists completed four visits: two under a placebo gum (GUMPLA) and two under GUMCAF ingestion. Each visit consisted of two square-wave cycling bouts at Δ70 intensity (70% of difference between the V˙O2 at first ventilatory threshold and V˙O2max) with duration of 6 min each and 5 min of passive rest between the bouts. The GUMPLA or GUMCAF (400 mg) was chewed for 5 min, 12 min before the first Δ70 bout in a randomized double-blind procedure. The fundamental phase and slow component of HHb + Mb and V˙O2 kinetics were evaluated. For HHb + Mb kinetics, regardless of ingested gum, priming exercise effects occurred on the time constant (GUMCAF 16.0 ± 4.0 vs. 13.9 ± 2.9 s; GUMPLA 15.7 ± 6.1 vs. 13.2 ± 2.5 s), amplitude, slow component, time delay, and mean response time parameters (p ≤ .032). For V˙O2 kinetics, there were significant effects of bouts on the amplitude, slow component, end V˙O2, and the gain kinetics parameters (p < .017). Baseline V˙O2 was higher during GUMCAF than GUMPLA (p = .020). No significant effects occurred for the interaction between gum and bout in any parameter of V˙O2 or HHb + Mb kinetics. Therefore, unlike the priming exercise in severe-intensity exercise, GUMCAF is not an effective strategy for improving V˙O2 or HHb + Mb kinetics acceleration.

Asunto(s)

Ciclismo , Cafeína , Goma de Mascar , Estudios Cruzados , Músculo Esquelético , Consumo de Oxígeno , Espectroscopía Infrarroja Corta , Humanos , Método Doble Ciego , Ciclismo/fisiología , Adulto , Masculino , Cafeína/administración & dosificación , Cafeína/farmacología , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Adulto Joven , Cinética , Ejercicio Físico/fisiología

RESUMEN

The aim was to investigate the long-term effects of metformin ingestion on high-intensity interval training on performance, glycogen concentration (GC), GLUT-4 content, and metabolomics outcomes in rats. Fifty male Wistar rats were randomly divided into baseline, metformin (500 mg daily), and control groups. Training consisted of 4 sets of 10 jumps with 30 s of passive recovery per day, 5 days/week for 8 weeks. The intensity equivalent was 50% of body mass (BM) in the first four weeks and 70% of BM in the last four weeks. The animals were submitted to a weekly jump test until exhaustion at 50% of BM. Serum and tissues were collected at baseline and after 4 and 8 weeks for biochemical and metabolomics analysis. The number of jumps increased in the Control group without a significant difference between groups at 4 and 8 weeks. GLUT4 was lower in the gastrocnemius muscle in the Metformin at the fourth week compared to Control (P=0.03) and compared to Metformin (P=0.02) and Control (P=0.01) at eight weeks. Hepatic and soleus GC were not altered by metformin. Gastrocnemius GC was lower after 8 weeks in the Metformin group compared to Control (P=0.01). Significantly lower levels of pyruvate and phenylalanine and higher levels of ethanol, formate, betaine, very low-density lipoprotein, low-density lipoprotein, and creatine were found in the Metformin compared to the Control. Although chronic administration of metformin decreased food intake and negatively influenced the synthesis of muscle glycogen, it did not significantly change physical performance compared to the Control.

Asunto(s)

Transportador de Glucosa de Tipo 4 , Glucógeno , Entrenamiento de Intervalos de Alta Intensidad , Hipoglucemiantes , Metabolómica , Metformina , Condicionamiento Físico Animal , Animales , Masculino , Ratas , Transportador de Glucosa de Tipo 4/metabolismo , Glucógeno/metabolismo , Glucógeno/análisis , Entrenamiento de Intervalos de Alta Intensidad/métodos , Hipoglucemiantes/farmacología , Hipoglucemiantes/administración & dosificación , Espectroscopía de Resonancia Magnética/métodos , Metformina/farmacología , Metformina/administración & dosificación , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Condicionamiento Físico Animal/fisiología , Rendimiento Físico Funcional , Distribución Aleatoria , Ratas Wistar , Factores de Tiempo

RESUMEN

Omega-3 (n3) is a polyunsaturated fatty acid well known for its anti-inflammatory and neuroprotective properties. Obesity is linked to chronic inflammation that disrupts metabolism, the intestine physiology and the central nervous system functioning. This study aims to determine if n3 supplementation can interfere with the effects of obesity on the mitochondrial activity, intestinal barrier, and neurotransmitter levels in the brain of Wistar rats that received cafeteria diet (CAF). We examined adipose tissue, skeletal muscle, plasma, intestine, and the cerebral cortex of four groups: CT (control diet), CTn3 (control diet with n3 supplementation), CAF, and CAFn3 (CAF and n3). Diets were offered for 13 weeks, with n3 supplementation in the final 5 weeks. Adipose tissue Electron Transport Chain complexes I, II, and III showed higher activity in CAF groups, as did complexes III and IV in skeletal muscle. Acetate levels in plasma were reduced in CAF groups, and Lipopolysaccharide (LPS) was higher in the CAF group but reduced in CAFn3 group. Claudin-5 in the intestine was lower in CAF groups, with no n3 supplementation effect. In the cerebral cortex, dopamine levels were decreased with CAF, which was reversed by n3. DOPAC, a dopamine metabolite, also showed a supplementation effect, and HVA, a diet effect. Serotonin levels increased in the CAF group that received supplementation. Therefore, we demonstrate disturbances in mitochondria, plasma, intestine and brain of rats submitted to CAF and the potential benefit of n3 supplementation in endotoxemia and neurotransmitter levels.

Asunto(s)

Ácidos Grasos Omega-3 , Obesidad , Ratas Wistar , Transmisión Sináptica , Animales , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/metabolismo , Obesidad/metabolismo , Masculino , Transmisión Sináptica/efectos de los fármacos , Ratas , Suplementos Dietéticos , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos

RESUMEN

To evaluate the effects of red and infrared wavelengths, separately and combined, on the inflammatory process and collagen deposition in muscle damage caused by B. leucurus venom. 112 mice were inoculated with diluted venom (0.6mg/kg) in the gastrocnemius muscle. The animals were divided into four groups: one control (CG) and three treatments, namely: 1) red laser (λ=660 nm) (RG), 2) infrared laser (λ=808 nm) (IG) and 3) red laser (λ=660 nm) + infrared (λ=808 nm) (RIG). Each group was subdivided into four subgroups, according to the duration of treatment application (applications every 24 hours over evaluation times of up to 144 hours). A diode laser was used (0.1 W, CW, 1J/point, ED: 10 J/cm2). Both wavelengths reduced the intensity of inflammation and the combination between them significantly intensified the anti-inflammatory response. Photobiomodulation also changed the type of inflammatory infiltrate observed and RIG had the highest percentage of mononuclear cells in relation to the other groups. Hemorrhage intensity was significantly lower in treated animals and RIG had the highest number of individuals in which this variable was classified as mild. As for collagen deposition, there was a significant increase in RG in relation to CG, in RIG in relation to CG and in RIG in relation to IG. Photobiomodulation proved to be effective in the treatment of inflammation and hemorrhage caused by B. leucurus venom and stimulated collagen deposition. Better results were obtained with the combined wavelengths.

Asunto(s)

Bothrops , Colágeno , Venenos de Crotálidos , Hemorragia , Inflamación , Terapia por Luz de Baja Intensidad , Músculo Esquelético , Animales , Ratones , Terapia por Luz de Baja Intensidad/métodos , Músculo Esquelético/efectos de la radiación , Músculo Esquelético/efectos de los fármacos , Hemorragia/patología , Colágeno/metabolismo , Colágeno/análisis , Venenos de Crotálidos/toxicidad , Rayos Infrarrojos , Masculino , Láseres de Semiconductores/uso terapéutico , Mordeduras de Serpientes/radioterapia

RESUMEN

The production and release of cortisol during stress responses are key regulators of growth in teleosts. Understanding the molecular responses to cortisol is crucial for the sustainable farming of rainbow trout (Oncorhynchus mykiss) and other salmonid species. While several studies have explored the genomic and non-genomic impacts of cortisol on fish growth and skeletal muscle development, the long-term effects driven by epigenetic mechanisms, such as cortisol-induced DNA methylation, remain unexplored. In this study, we analyzed the transcriptome and genome-wide DNA methylation in the skeletal muscle of rainbow trout seven days after cortisol administration. We identified 550 differentially expressed genes (DEGs) by RNA-seq and 9059 differentially methylated genes (DMGs) via whole-genome bisulfite sequencing (WGBS) analysis. KEGG enrichment analysis showed that cortisol modulates the differential expression of genes associated with nucleotide metabolism, ECM-receptor interaction, and the regulation of actin cytoskeleton pathways. Similarly, cortisol induced the differential methylation of genes associated with focal adhesion, adrenergic signaling in cardiomyocytes, and Wnt signaling. Through integrative analyses, we determined that 126 genes showed a negative correlation between up-regulated expression and down-regulated methylation. KEGG enrichment analysis of these genes indicated participation in ECM-receptor interaction, regulation of actin cytoskeleton, and focal adhesion. Using RT-qPCR, we confirmed the differential expression of lamb3, itga6, limk2, itgb4, capn2, and thbs1. This study revealed for the first time the molecular responses of skeletal muscle to cortisol at the transcriptomic and whole-genome DNA methylation levels in rainbow trout.

Asunto(s)

Metilación de ADN , Hidrocortisona , Músculo Esquelético , Oncorhynchus mykiss , Estrés Fisiológico , Transcriptoma , Animales , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/metabolismo , Hidrocortisona/metabolismo , Hidrocortisona/farmacología , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Estrés Fisiológico/genética , Epigénesis Genética , Epigenómica/métodos , Perfilación de la Expresión Génica , Proteínas de Peces/genética , Proteínas de Peces/metabolismo

RESUMEN

Muscular dystrophies (MDs) are a heterogeneous group of diseases of genetic origin characterized by progressive skeletal muscle degeneration and weakness. There are several types of MDs, varying in terms of age of onset, severity, and pattern of the affected muscles. However, all of them worsen over time, and many patients will eventually lose their ability to walk. In addition to skeletal muscle effects, patients with MDs may present cardiac and respiratory disorders, generating complications that could lead to death. Interdisciplinary management is required to improve the surveillance and quality of life of patients with an MD. At present, pharmacological therapy is only available for Duchene muscular dystrophy (DMD)-the most common type of MD-and is mainly based on the use of corticosteroids. Other MDs caused by alterations in dystrophin-associated proteins (DAPs) are less frequent but represent an important group within these diseases. Pharmacological alternatives with clinical potential in patients with MDs and other proteins associated with dystrophin have been scarcely explored. This review focuses on drugs and molecules that have shown beneficial effects, mainly in experimental models involving alterations in DAPs. The mechanisms associated with the effects leading to promising results regarding the recovery or maintenance of muscle strength and reduction in fibrosis in the less-common MDs (i.e., with respect to DMD) are explored, and other therapeutic targets that could contribute to maintaining the homeostasis of muscle fibers, involving different pathways, such as calcium regulation, hypertrophy, and maintenance of satellite cell function, are also examined. It is possible that some of the drugs explored here could be used to affordably improve the muscular function of patients until a definitive treatment for MDs is developed.

Asunto(s)

Distrofias Musculares , Humanos , Distrofias Musculares/tratamiento farmacológico , Distrofias Musculares/fisiopatología , Distrofina , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Distrofia Muscular de Duchenne/tratamiento farmacológico , Distrofia Muscular de Duchenne/fisiopatología , Complejo de Proteínas Asociado a la Distrofina

RESUMEN

Sarcopenia in cancer patients often negatively impacts various outcomes. Carboplatin, a first-line chemotherapy for non-small cell lung cancer (NSCLC), is dosed based on body weight, which doesn't account for sarcopenia. This study evaluated the association between sarcopenia and carboplatin-related toxicity in NSCLC patients. Patients with locally advanced or metastatic NSCLC treated with carboplatin were included. Toxicity events during the first two cycles of treatment were recorded. Sarcopenia was assessed using pretreatment computed tomography scans analyzed with Slice-O-Matic V4.2 software, defining sarcopenia as a skeletal muscle index (SMI) of <52.4 cm2/m2 for men and <38.5 cm2/m2 for women. Among 146 patients, 52% had sarcopenia. Hematological toxicity occurred in 71.2% of all patients and 77.6% of those with sarcopenia. The fat-free mass index (FFMI) was independently associated with hematological toxicity and dose-limiting toxicity (DLT), which was observed in 55.5% of patients. Sarcopenia significantly correlates with hematological toxicity and DLT during carboplatin treatment in NSCLC patients. Given its prevalence and noninvasive detection, further research is needed to understand its impact on treatment outcomes.

Asunto(s)

Carboplatino , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Sarcopenia , Humanos , Carboplatino/efectos adversos , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Sarcopenia/inducido químicamente , Femenino , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Persona de Mediana Edad , Antineoplásicos/efectos adversos , Tomografía Computarizada por Rayos X , Estudios Retrospectivos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Músculo Esquelético/diagnóstico por imagen

RESUMEN

Alloxan-induced diabetic rats present with hypothyroidism. When treated with triiodothyronine (T3), glycemia and proinflammatory cytokine expression are downregulated, improving insulin sensitivity. The effectiveness of associating T3 with insulin (replacement dose [6 U] and [3 U]) in controlling glycemia was investigated in this experimental model. Male Wistar rats were made diabetic by alloxan injection and sorted into groups treated or not with insulin (3 or 6 U) associated or not with T3 (1.5 µg 100 g-1 BW) for 28 days. Nondiabetic rats constituted the control group. Fasting glycemia, glucose decay rate, and thyrotropin (TSH) were measured in the blood/serum of all animals. Immunoblotting was used to assess total GLUT4 expression in skeletal muscles and epididymal white adipose tissue. Cytokine and nuclear factor-κB (NF-κB) expression were measured in these tissues and liver. Diabetic rats presented with increased fasting glycemia, inflammatory cytokines, and NF-κB expression, TSH levels, and insulin resistance. In diabetic rats treated with T3 and/or insulin, these parameters were decreased, whereas GLUT4 and anti-inflammatory cytokine expression were increased. T3 combined with 3-U insulin restored the parameters to values of the control group and was more effective at controlling glycemia than 6-U insulin. Thus, a combination of T3 and insulin might represent a promising strategy for diabetes management since it reduces the insulin requirement by half and improves glycemic control of diabetic rats, which could postpone insulin resistance that develops with chronic insulin administration. These findings open a perspective for using thyroid analogues that provide tissue-specific effects, which might result in a potentially more effective treatment of diabetes.

Asunto(s)

Glucemia , Diabetes Mellitus Experimental , Transportador de Glucosa de Tipo 4 , Insulina , FN-kappa B , Ratas Wistar , Triyodotironina , Animales , Masculino , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Triyodotironina/sangre , Triyodotironina/farmacología , Ratas , Transportador de Glucosa de Tipo 4/metabolismo , Glucemia/metabolismo , Glucemia/efectos de los fármacos , FN-kappa B/metabolismo , Resistencia a la Insulina , Aloxano , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Tirotropina/sangre , Citocinas/metabolismo , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico

RESUMEN

Increasing evidence hints that DNA hypermethylation may mediate the pathogenic response to cardiovascular risk factors. Here, we tested a corollary of that hypothesis, that is, that the DNA methyltransferase inhibitor decitabine (Dec) ameliorates the metabolic profile of mice fed a moderately high-animal fat and protein diet (HAFPD), a proxy of cardiovascular risk-associated Western-type diet. HAFPD-fed mice were exposed to Dec or vehicle for eight weeks (8W set, 4-32/group). To assess any memory of past exposure to Dec, we surveyed a second mice set treated as 8W but HAFPD-fed for further eight weeks without any Dec (16W set, 4-20/group). In 8W, Dec markedly reduced HAFPD-induced body weight gain in females, but marginally in males. Characterization of females revealed that Dec augmented skeletal muscle lipid content, while decreasing liver fat content and increasing plasma nonesterified fatty acids, adipose insulin resistance, and-although marginally-whole blood acylcarnitines, compared to HAFPD alone. Skeletal muscle mitochondrial DNA copy number was higher in 8W mice exposed to HAFPD and Dec, or in 16W mice fed HAFPD only, relative to 8W mice fed HAFPD only, but Dec induced a transcriptional profile indicative of ameliorated mitochondrial function. Memory of past Dec exposure was tissue-specific and sensitive to both duration of exposure to HAFPD and age. In conclusion, Dec redirected HAFPD-induced lipid accumulation toward the skeletal muscle, likely due to augmented mitochondrial functionality and increased lipid demand. As caveat, Dec induced adipose insulin resistance. Our findings may help identifying strategies for prevention and treatment of lipid dysmetabolism.

Asunto(s)

Decitabina , Dieta Alta en Grasa , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Femenino , Decitabina/farmacología , Masculino , Ratones Endogámicos C57BL , Proteínas en la Dieta/farmacología , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Metilación de ADN/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Resistencia a la Insulina

RESUMEN

Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain accompanied by fatigue and muscle atrophy. Although its etiology is not known, studies have shown that FM patients exhibit altered function of the sympathetic nervous system (SNS), which regulates nociception and muscle plasticity. Nevertheless, the precise SNS-mediated mechanisms governing hyperalgesia and skeletal muscle atrophy in FM remain unclear. Thus, we employed two distinct FM-like pain models, involving intramuscular injections of acidic saline (pH 4.0) or carrageenan in prepubertal female rats, and evaluated the catecholamine content, adrenergic signaling and overall muscle proteolysis. Subsequently, we assessed the contribution of the SNS to the development of hyperalgesia and muscle atrophy in acidic saline-injected rats treated with clenbuterol (a selective ß2-adrenergic receptor agonist) and in animals maintained under baseline conditions and subjected to epinephrine depletion through adrenodemedullation (ADM). Seven days after inducing an FM-like model with acidic saline or carrageenan, we observed widespread mechanical hyperalgesia along with loss of strength and/or muscle mass. These changes were associated with reduced catecholamine content, suggesting a common underlying mechanism. Notably, treatment with a ß2-agonist alleviated hyperalgesia and prevented muscle atrophy in acidic saline-induced FM-like pain, while epinephrine depletion induced mechanical hyperalgesia and increased muscle proteolysis in animals under baseline conditions. Together, the results suggest that reduced sympathetic activity is involved in the development of pain and muscle atrophy in the murine model of FM analyzed.

Asunto(s)

Clenbuterol , Modelos Animales de Enfermedad , Fibromialgia , Hiperalgesia , Atrofia Muscular , Sistema Nervioso Simpático , Animales , Femenino , Fibromialgia/patología , Fibromialgia/fisiopatología , Atrofia Muscular/patología , Atrofia Muscular/fisiopatología , Hiperalgesia/fisiopatología , Hiperalgesia/patología , Sistema Nervioso Simpático/fisiopatología , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/patología , Clenbuterol/farmacología , Ratas , Carragenina/toxicidad , Ratas Sprague-Dawley , Dolor/patología , Dolor/fisiopatología , Epinefrina , Músculo Esquelético/patología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Catecolaminas/metabolismo , Agonistas Adrenérgicos beta/farmacología

RESUMEN

This study aimed to evaluate the effect of including soybean molasses (SM) on performance, blood parameters, carcass traits, meat quality, fatty acid, and muscle (longissimus thoracis) transcriptomic profiles of castrated lambs. Twenty Dorper × Santa Inês lambs (20.06 ±â€…0.76 kg body weight [BW]) were assigned to a randomized block design, stratified by BW, with the following treatments: CON: 0 g/kg of SM and SM20: 200 g/kg of SM on dry matter basis, allocated in individual pens. The diet consisted of 840 g/kg concentrate and 160 g/kg corn silage for 76 d, with the first 12 d as an adaptation period and the remaining 64 d on the finishing diet. The SM20 diet increased blood urea concentration (P = 0.03) while reduced glucose concentration (P = 0.04). Lambs fed SM showed higher subcutaneous fat deposition (P = 0.04) and higher subcutaneous adipocyte diameter (P < 0.01), in addition to reduced meat lipid oxidation (P < 0.01). SM reduced the quantity of branched-chain fatty acids in longissimus thoracis (P = 0.05) and increased the quantity of saturated fatty acids (P = 0.01). In the transcriptomic analysis, 294 genes were identified as differentially expressed, which belong to pathways such as oxidative phosphorylation, citric acid cycle, and monosaccharide metabolic process. In conclusion, diet with SM increased carcass fat deposition, reduced lipid oxidation, and changed the energy metabolism, supporting its use in ruminant nutrition.

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This study investigated the effects of incorporating soybean molasses (SM) into the diet of castrated lambs on various aspects of their performance and meat quality. Twenty lambs were divided into two groups: one was fed a control diet without SM whereas the other was fed a similar diet but containing 20% of SM. The feeding trial lasted for 76 d. Results showed that the SM inclusion in the diet led to increased blood urea levels and decreased glucose concentrations. SM inclusion also resulted in lambs with higher levels of subcutaneous fat and larger adipocytes, while reducing meat lipid oxidation. Moreover, SM altered fatty acid composition in the meat, decreasing branched-chain fatty acids and increasing saturated fatty acids. In agreement with these findings, transcriptomic analysis revealed a significant change in the expression of genes related to energy metabolism in the muscle of lambs fed SM. In conclusion, incorporating SM in lamb's diet increased fat deposition, improved meat quality, and induced a transcriptomic change in the muscle energy metabolism, supporting its potential use in ruminant nutrition.

Asunto(s)

Alimentación Animal , Dieta , Glycine max , Metabolismo de los Lípidos , Carne , Melaza , Grasa Subcutánea , Animales , Alimentación Animal/análisis , Dieta/veterinaria , Glycine max/química , Grasa Subcutánea/metabolismo , Grasa Subcutánea/efectos de los fármacos , Masculino , Carne/análisis , Metabolismo de los Lípidos/efectos de los fármacos , Ovinos , Fenómenos Fisiológicos Nutricionales de los Animales , Ácidos Grasos/metabolismo , Distribución Aleatoria , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Oxidación-Reducción , Oveja Doméstica , Suplementos Dietéticos/análisis

RESUMEN

The use of creatine monohydrate (Cr) in professional soccer is widely documented. However, the effect of low doses of Cr on the physical performance of young soccer players is unknown. This study determined the effect of a low dose of orally administered Cr on muscle power after acute intra-session fatigue in young soccer players. Twenty-eight young soccer players (mean age = 17.1 ± 0.9 years) were randomly assigned to either a Cr (n = 14, 0.3 g·kg-1·day-1 for 14 days) or placebo group (n = 14), using a two-group matched, double-blind, placebo-controlled design. Before and after supplementation, participants performed 21 repetitions of 30 m (fatigue induction), and then, to measure muscle power, they performed four repetitions in half back squat (HBS) at 65% of 1RM. Statistical analysis included a two-factor ANOVA (p ˂ 0.05). Bar velocity at HBS, time: p = 0.0006, ŋp2 = 0.22; group: p = 0.0431, ŋp2 = 0.12, time × group p = 0.0744, ŋp2 = 0.02. Power at HBS, time: p = 0.0006, ŋp2 = 0.12; group: p = 0.16, ŋp2 = 0.06, time × group: p = 0.17, ŋp2 = 0.009. At the end of the study, it was found that, after the induction of acute intra-session fatigue, a low dose of Cr administered orally increases muscle power in young soccer players.

Asunto(s)

Creatina , Suplementos Dietéticos , Fatiga Muscular , Fuerza Muscular , Fútbol , Humanos , Fútbol/fisiología , Creatina/administración & dosificación , Adolescente , Método Doble Ciego , Masculino , Fatiga Muscular/efectos de los fármacos , Administración Oral , Fuerza Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Rendimiento Atlético/fisiología , Atletas

RESUMEN

Camelid single-domain antibodies (VHH) represent a promising class of immunobiologicals for therapeutic applications due to their remarkable stability, specificity, and therapeutic potential. To enhance the effectiveness of antivenoms for snakebites, various methods have been explored to address limitations associated with serum therapy, particularly focusing on mitigating local damage and ensuring sustainable production. Our study aimed to characterize the pharmacological profile and neutralization capacity of anti-Phospholipase A2 (PLA2) monomeric VHH (Genbank accessions: KC329718). Using a post-envenoming mouse model, we used intravital microscopy to assess leukocyte influx, measured CK and LDH levels, and conducted a histopathology analysis to evaluate VHH KC329718's ability to neutralize myotoxic activity. Our findings demonstrated that VHH KC329718 exhibited heterogeneous distribution in muscle tissue. Treatment with VHH KC329718 reduced leukocyte influx caused by BthTX-I (a Lys-49 PLA2) by 28 %, as observed through intravital microscopy. When administered at a 1:10 ratio [venom or toxin:VHH (w/w)], VHH KC329718 significantly decreased myotoxicity, resulting in a 35-40 % reduction in CK levels from BthTX-I and BthTX-II (an Asp-49 PLA2) and a 60 % decrease in CK levels from B. jararacussu venom. LDH levels also showed reductions of 60%, 80%, and 60% induced by BthTX-I, BthTX-II, and B. jararacussu venom, respectively. Histological analysis confirmed the neutralization potential, displaying a significant reduction in tissue damage and inflammatory cell count in mice treated with VHH KC329718 post B. jararacussu venom inoculation. This study underscores the potential of monomeric anti-PLA2 VHH in mitigating myotoxic effects, suggesting a promising avenue for the development of new generation antivenoms to address current therapeutic limitations.

Asunto(s)

Antivenenos , Bothrops , Fosfolipasas A2 , Anticuerpos de Dominio Único , Mordeduras de Serpientes , Animales , Anticuerpos de Dominio Único/inmunología , Mordeduras de Serpientes/tratamiento farmacológico , Mordeduras de Serpientes/inmunología , Antivenenos/farmacología , Antivenenos/uso terapéutico , Ratones , Fosfolipasas A2/metabolismo , Venenos de Crotálidos/inmunología , Venenos de Crotálidos/toxicidad , Masculino , Modelos Animales de Enfermedad , Músculo Esquelético/patología , Músculo Esquelético/efectos de los fármacos , Leucocitos/efectos de los fármacos , Leucocitos/inmunología , Humanos , Creatina Quinasa/sangre

RESUMEN

Cadmium (Cd) is a heavy metal that acts as endocrine disrupting chemical (EDC). Few studies have investigated the effects of Cd exposure on metabolic dysfunctions, such as type 1 and 2 diabetes mellitus (T1DM and T2DM). Thus, we assessed whether subacute Cd exposure at occupational levels causes abnormalities in white adipose tissue (WAT), liver, pancreas, and skeletal muscle. We administered cadmium chloride (CdCl2) (100 ppm in drinking water for 30 days) to female rats and evaluated Cd levels in serum and metabolic organs, morphophysiology, inflammation, oxidative stress, fibrosis, and gene expression. High Cd levels were found in serum, WAT, liver, pancreas, and skeletal muscle. Cd-exposed rats showed low adiposity, dyslipidemia, insulin resistance, systemic inflammation, and oxidative stress compared to controls. Cd exposure reduced adipocyte size, hyperleptinemia, increased cholesterol levels, inflammation, apoptosis and fibrosis in WAT. Cd-exposed rats had increased liver cholesterol levels, insulin receptor beta (IRß) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1α) expression, karyomegaly, inflammation, and fibrosis. Cd exposure reduced insulin levels and pancreatic islet size and increased inflammation and fibrosis. Cd exposure reduced skeletal muscle fiber diameter and increased IR expression and inflammation. Finally, strong positive correlations were observed between serum, tissue Cd levels, abnormal morphology, tissue inflammation and fibrosis. Thus, these data suggest that subacute Cd exposure impairs WAT, liver, pancreas and skeletal muscle function, leading to T1DM and T2DM features and other complications in female rats.

Asunto(s)

Cadmio , Diabetes Mellitus Tipo 2 , Hígado , Animales , Femenino , Diabetes Mellitus Tipo 2/inducido químicamente , Ratas , Cadmio/toxicidad , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Estrés Oxidativo/efectos de los fármacos , Diabetes Mellitus Tipo 1/inducido químicamente , Ratas Wistar , Páncreas/efectos de los fármacos , Páncreas/patología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Disruptores Endocrinos/toxicidad

RESUMEN

High sodium intake is decisive in the incidence increase and prevalence of hypertension, which has an impact on skeletal muscle functionality. Diazoxide is an antihypertensive agent that inhibits insulin secretion and is an opener of KATP channels (adosine triphosphate sensitive potasium channels). For this reason, it is hypothesized that moderate-intensity exercise and diazoxide improve skeletal muscle function by reducing the oxidants in hypertensive rats. Male Wistar rats were assigned into eight groups: control (CTRL), diazoxide (DZX), exercise (EX), exercise + diazoxide (EX + DZX), hypertension (HTN), hypertension + diazoxide (HTN + DZX), hypertension + exercise (HTN + EX), and hypertension + exercise + diazoxide (HTN + EX + DZX). To induce hypertension, the rats received 8% NaCl dissolved in water orally for 30 days; in the following 8 weeks, 4% NaCl was supplied to maintain the pathology. The treatment with physical exercise of moderate intensity lasted 8 weeks. The administration dose of diazoxide was 35 mg/kg intraperitoneally for 14 days. Tension recording was performed on the extensor digitorum longus and the soleus muscle. Muscle homogenates were used to measure oxidants using fluorescent probe and the activity of antioxidant systems. Diazoxide and moderate-intensity exercise reduced oxidants and increased antioxidant defenses.

Asunto(s)

Antioxidantes , Diazóxido , Hipertensión , Músculo Esquelético , Condicionamiento Físico Animal , Ratas Wistar , Animales , Diazóxido/farmacología , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Hipertensión/metabolismo , Hipertensión/fisiopatología , Condicionamiento Físico Animal/fisiología , Ratas , Antioxidantes/metabolismo , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Oxidantes/metabolismo