GILSON MASAHIRO MURATA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
9 resultados
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- Effects of Resistance Exercise on Slow-Twitch Soleus Muscle of Infarcted Rats(2023) SOUZA, Lidiane Moreira; GOMES, Mariana Janini; BRANDAO, Bruna Brasil; PAGAN, Luana Urbano; GATTO, Mariana; DAMATTO, Felipe Cesar; RODRIGUES, Eder Anderson; PONTES, Thierres Hernani Dias; BORIM, Patricia Aparecida; FERNANDES, Ana Angelica Henrique; MURATA, Gilson Masahiro; ZORNOFF, Leonardo Antonio Mamede; AZEVEDO, Paula Schmidt; OKOSHI, Katashi; OKOSHI, Marina PolitiAlthough current guidelines recommend resistance exercise in combination with aerobic training to increase muscle strength and prevent skeletal muscle loss during cardiac remodeling, its effects are not clear. In this study, we evaluated the effects of resistance training on cardiac remodeling and the soleus muscle in long-term myocardial infarction (MI) rats. Methods: Three months after MI induction, male Wistar rats were assigned to Sham (n = 14), MI (n = 9), and resistance exercised MI (R-MI, n = 13) groups. The rats trained three times a week for 12 weeks on a climbing ladder. An echocardiogram was performed before and after training. Protein expression of the insulin-like growth factor (IGF)-1/protein kinase B (Akt)/rapamycin target complex (mTOR) pathway was analyzed by Western blot. Results: Mortality rate was higher in MI than Sham; in the R-MI group, mortality rate was between that in MI and Sham and did not differ significantly from either group. Exercise increased maximal load capacity without changing cardiac structure and left ventricular function in infarcted rats. Infarction size did not differ between infarcted groups. Catalase activity was lower in MI than Sham and glutathione peroxidase lower in MI than Sham and R-MI. Protein expression of p70S6K was lower in MI than Sham and p-FoxO3 was lower in MI than Sham and R-MI. Energy metabolism did not differ between groups, except for higher phosphofrutokinase activity in R-MI than MI. Conclusion: Resistance exercise is safe and increases muscle strength regardless structural and functional cardiac changes in myocardial-infarcted rats. This exercise modality attenuates soleus glycolytic metabolism changes and improves the expression of proteins required for protein turnover and antioxidant response.
- Influence of Isolated Resistance Exercise on Cardiac Remodeling, Myocardial Oxidative Stress, and Metabolism in Infarcted Rats(2023) RODRIGUES, Eder Anderson; LIMA, Aline Regina Ruiz; GOMES, Mariana Janini; SOUZA, Lidiane Moreira; PONTES, Thierres Hernani Dias; PAGAN, Luana Urbano; MURATA, Gilson Masahiro; DAMATTO, Felipe Cesar; DEPRA, Igor Carvalho; REGO, Amanda Bergamo Goncalves Castro; REYES, David Rafael Abreu; ZORNOFF, Leonardo Antonio Mamede; OKOSHI, Katashi; OKOSHI, Marina PolitiIntroduction: Exercise is an important therapeutic strategy for preventing and treating myocardial infarction (MI)-induced cardiac remodeling and heart failure. However, the myocardial effects of resistance exercise on infarcted hearts are not completely established. In this study, we investigated the effects of resistance exercise on structural, functional, and molecular cardiac alterations in infarcted rats. Methods: Three months after MI induction or simulated surgery, Wistar rats were assigned into three groups: Sham (n = 14); MI (n = 9); and exercised MI (MI-Ex, n = 13). Exercised rats performed, 3 times a week for 12 weeks, four climbs on a ladder with progressive loads. Cardiac structure and left ventricle (LV) function were analyzed by echocardiogram. Myocyte diameters were evaluated in hematoxylin- and eosin-stained histological sections as the smallest distance between borders drawn across the nucleus. Myocardial energy metabolism, lipid hydroperoxide, malondialdehyde, protein carbonylation, and antioxidant enzyme activities were evaluated by spectrophotometry. Gene expressions of NADPH oxidase subunits were evaluated by RT-PCR. Statistical analyses were performed using ANOVA and Tukey or Kruskal-Wallis and Dunn's test. Results: Mortality did not differ between the MI-Ex and MI groups. MI had dilated left atrium and LV, with LV systolic dysfunction. Exercise increased the maximum load-carrying capacity, with no changes in cardiac structure or LV function. Myocyte diameters were lower in MI than in Sham and MI-Ex. Lactate dehydrogenase and creatine kinase activity were lower in MI than in Sham. Citrate synthase and catalase activity were lower in MI and MI-Ex than in Sham. Lipid hydroperoxide concentration was lower in MI-Ex than in MI. Nox2 and p22phox gene expressions were higher in MI-Ex than in Sham. Gene expression of Nox4 was higher in MI and MI-Ex than in Sham, and p47phox was lower in MI than in Sham. Conclusion: Late resistance exercise was safe in infarcted rats. Resistance exercise improved maximum load-carrying capacity, reduced myocardial oxidative stress, and preserved myocardial metabolism, with no changes in cardiac structure or left ventricle function in infarcted rats.
- The influence of dapagliflozin on cardiac remodeling, myocardial function and metabolomics in type 1 diabetes mellitus rats(2023) RODRIGUES, Eder Anderson; ROSA, Camila Moreno; CAMPOS, Dijon Henrique Salome; DAMATTO, Felipe Cesar; MURATA, Gilson Masahiro; SOUZA, Lidiane Moreira; PAGAN, Luana Urbano; GATTO, Mariana; BROSLER, Jessica Yumi; SOUZA, Hebreia Oliveira Almeida; MARTINS, Mario Machado; BASTOS, Luciana Machado; TANNI, Suzana Erico; OKOSHI, Katashi; OKOSHI, Marina PolitiBackgroundSodium-glucose cotransporter (SGLT)2 inhibitors have displayed beneficial effects on the cardiovascular system in diabetes mellitus (DM) patients. As most clinical trials were performed in Type 2 DM, their effects in Type 1 DM have not been established.ObjectiveTo evaluate the influence of long-term treatment with SGLT2 inhibitor dapagliflozin on cardiac remodeling, myocardial function, energy metabolism, and metabolomics in rats with Type 1 DM.MethodsMale Wistar rats were divided into groups: Control (C, n = 15); DM (n = 15); and DM treated with dapagliflozin (DM + DAPA, n = 15) for 30 weeks. DM was induced by streptozotocin. Dapagliflozin 5 mg/kg/day was added to chow. Statistical analysis: ANOVA and Tukey or Kruskal-Wallis and Dunn.ResultsDM + DAPA presented lower glycemia and higher body weight than DM. Echocardiogram showed DM with left atrium dilation and left ventricular (LV) hypertrophy, dilation, and systolic and diastolic dysfunction. In LV isolated papillary muscles, DM had reduced developed tension, +dT/dt and -dT/dt in basal condition and after inotropic stimulation. All functional changes were attenuated by dapagliflozin. Hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) activity was lower in DM than C, and PFK and PK activity higher in DM + DAPA than DM. Metabolomics revealed 21 and 5 metabolites positively regulated in DM vs. C and DM + DAPA vs. DM, respectively; 6 and 3 metabolites were negatively regulated in DM vs. C and DM + DAPA vs. DM, respectively. Five metabolites that participate in cell membrane ultrastructure were higher in DM than C. Metabolites levels of N-oleoyl glutamic acid, chlorocresol and N-oleoyl-L-serine were lower and phosphatidylethanolamine and ceramide higher in DM + DAPA than DM.ConclusionLong-term treatment with dapagliflozin attenuates cardiac remodeling, myocardial dysfunction, and contractile reserve impairment in Type 1 diabetic rats. The functional improvement is combined with restored pyruvate kinase and phosphofructokinase activity and attenuated metabolomics changes.
- A short-term high-sugar diet is an aggravating factor in experimental allergic contact dermatitis(2023) COELHO, Leila F.; CASARO, Mateus B.; RIBEIRO, Willian R.; MENDES, Eduardo; MURATA, Gilson; XANDER, Patricia; LINO-DOS-SANTOS-FRANCO, Adriana; OLIVEIRA, Fernando A.; FERREIRA, Caroline M.Allergic contact dermatitis (ACD) is an inflammatory skin reaction whose incidence has increased and has been associated with a dietary pattern rich in saturated fats and refined sugars. Considering the increased incidence of ACD and the lack of research about the influence of a short-term high-sugar diet on dermatitis, our aim is to improve understanding of the influence of a high-sugar diet on ACD. We introduced a diet rich in sugar fifteen days before inducing contact dermatitis with oxazolone, in mice, and maintained it until the end of the experiment, which lasted three weeks in total. The dermatitis model increased cholesterol and triglycerides in the liver, and the combination of diet and dermatitis increased weight and worsened liver cholesterol measurements. Furthermore, the high-sugar diet increased the production of IL-6, IFN-gamma and TNF alpha in the skin, which may be involved in the increase in epithelial skin thickness observed in experimental ACD.
- Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure(2023) SANT'ANA, Paula Grippa; TOMASI, Loreta Casquel de; MURATA, Gilson Masahiro; VILEIGAS, Danielle Fernandes; MOTA, Gustavo Augusto Ferreira; SOUZA, Sergio Luiz Borges de; SILVA, Vitor Loureiro; CAMPOS, Livia Paschoalino de; OKOSHI, Katashi; PADOVANI, Carlos Roberto; CICOGNA, Antonio CarlosIn pathological cardiac hypertrophy, the heart is more dependent on glucose than fatty acids. This shift in energy metabolism occurs due to several factors, including the oxygen deficit, which activates hypoxia-inducible factor-1a (HIF-1a), a critical molecule related to glucose metabolism. However, there are gaps regarding the behavior of key proteins in the glycolytic pathway and HIF-1a during the transition from hypertrophy to heart failure (HF). This study assesses the hypothesis that there is an early change and enhancement of HIF-1a and the glycolytic pathway, as well as an association between them during cardiac remodeling. Sham and aortic stenosis Wistar rats were analyzed at 2, 6, and 18 weeks and in HF (n = 10-18). Cardiac structure and function were investigated by echocardiogram. Myocardial glycolysis, the aerobic and anaerobic pathways and glycogen were analyzed by enzymatic assay, Western blot, and enzyme-linked immunosorbent assay (ELISA). The following were observed: increased left ventricular hypertrophy; early diastolic function change and severe systolic and diastolic dysfunction in HF; increased HIF-1a in the 2nd week and in HF; precocious alteration and intensification of glycolysis with a shift to anaerobic metabolism from the 6th week onwards; association between HIF-1a, glycolysis, and the anaerobic pathway. Our hypothesis was confirmed as there was an early change and intensification in glucose metabolism, alteration in HIF-1a, and an association between data during the progression from hypertrophy to heart failure.
- Estradiol Protects Female ApoE KO Mice against Western-Diet-Induced Non-Alcoholic Steatohepatitis(2023) ARAUJO, Layanne C. C.; CRUZ, Alessandra G.; CAMARGO, Felipe N.; SUCUPIRA, Felipe G.; MOREIRA, Gabriela V.; MATOS, Sandro L.; AMARAL, Andressa G.; MURATA, Gilson Masahiro; CARVALHO, Carla R. O.; CAMPOREZ, Joao PauloThe prevalence of non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), is higher in men than in women of reproductive age, and postmenopausal women are especially susceptible to developing the disease. Aim: we evaluated if female apolipoprotein E (ApoE) KO mice were protected against Western-diet (WD)-induced NASH. Methods: Female ovariectomized (OVX) ApoE KO mice or sham-operated (SHAM) mice were fed either a WD or a regular chow (RC) for 7 weeks. Additionally, OVX mice fed a WD were treated with either estradiol (OVX + E2) or vehicle (OVX). Results: Whole-body fat, plasma glucose, and plasma insulin were increased and associated with increased glucose intolerance in OVX mice fed a WD (OVX + WD). Plasma and hepatic triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) hepatic enzymes were also increased in the plasma of OVX + WD group, which was associated with hepatic fibrosis and inflammation. Estradiol replacement in OVX mice reduced body weight, body fat, glycemia, and plasma insulin associated with reduced glucose intolerance. Treatment also reduced hepatic triglycerides, ALT, AST, hepatic fibrosis, and inflammation in OVX mice. Conclusions: These data support the hypothesis that estradiol protects OVX ApoE KO mice from NASH and glucose intolerance.
- Novel Nutraceutical (silymarin, yeast & beta;-glucan, prebiotics, and minerals) shifts gut microbiota and restores large intestine histology of diet-induced metabolic syndrome mice(2023) NEHMI-FILHO, Victor; FREITAS, Jessica Alves de; FRANCO, Lucas Augusto Moyses; FONSECA, Joyce Vanessa da Silva; MARTINS, Roberta Cristina Ruedas; SANTAMARINA, Aline Boveto; MURATA, Gilson Masahiro; SABINO, Ester Cerdeira; SOUZA, Erica; FERREIRA, Matthew Thomas; OTOCH, Jose Pinhata; PESSOA, Ana Flavia MarcalGut dysbiosis contributes to chronic inflammation and oxidative stress associated with metabolic syndrome, and non-pharmacological, health-promoting supplements like nutraceuticals have been studied and used as a way to prevent or treat several illnesses. Thus, male C57BL/6 mice were divided into the following groups: control (CTL) _Vehicle and CTL_Nutraceutical; high-fat diet (HFD)_Vehicle, HFD_Nutraceutical, HFD_Nutraceutical_S, and isolated compounds. The vehicle and experimental formulations were administered by gavage once a day for four weeks with a high-fat diet simultaneously. In addition, we evaluated the composition of the fecal microbiota by partial 16S rRNA sequences directly amplified using a bacterial/archaeal primer set 515F/806R, and large intestine histomorphology was examined by H & E (Hematoxylin and Eosin), Masson's trichrome (MT), and PAS-AB (Periodic Acid Schiff-Alcian Blue) stains in these groups of mice. After four weeks of supplementation, only the Novel Nutraceutical supplement was able to increase & alpha; and & beta;-diversities, modulate the relative abundance in gut microbiota, decrease Firmicutes, and increase Bacteroidetes bacteria, meanwhile recovering the large intestine's (colon) histomorphology in CTL and HFD groups.
- Changes in Skeletal Muscle Protein Metabolism Signaling Induced by Glutamine Supplementation and Exercise(2023) JR, Carlos Flores Rodrigues; MURATA, Gilson Masahiro; GERLINGER-ROMERO, Frederico; NACHBAR, Renato Tadeu; MARZUCA-NASSR, Gabriel Nasri; GORJAO, Renata; VITZEL, Kaio Fernando; HIRABARA, Sandro Massao; PITHON-CURI, Tania Cristina; CURI, RuiAim: 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 degrees 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.
- Effects of early exercise on cardiac function and lipid metabolism pathway in heart failure(2023) SOUZA, Sergio Luiz Borges de; MOTA, Gustavo Augusto Ferreira; SILVA, Vitor Loureiro da; VILEIGAS, Danielle Fernandes; SANT'ANA, Paula Grippa; GREGOLIN, Cristina Schmitt; FIGUEIRA, Rebeca Lopes; BATAH, Sabrina Setembre; FABRO, Alexandre Todorovic; MURATA, Gilson Masahiro; BAZAN, Silmeia Garcia Zanati; OKOSHI, Marina Politi; CICOGNA, Antonio CarlosWe employed an early training exercise program, immediately after recovery from surgery, and before severe cardiac hypertrophy, to study the underlying mechanism involved with the amelioration of cardiac dysfunction in aortic stenosis (AS) rats. As ET induces angiogenesis and oxygen support, we aimed to verify the effect of exercise on myocardial lipid metabolism disturbance. Wistar rats were divided into Sham, trained Sham (ShamT), AS and trained AS (AST). The exercise consisted of 5-week sessions of treadmill running for 16 weeks. Statistical analysis was conducted by anova or Kruskal-Wallis test and Goodman test. A global correlation between variables was also performed using a two-tailed Pearson's correlation test. AST rats displayed a higher functional capacity and a lower cardiac remodelling and dysfunction when compared to AS, as well as the myocardial capillary rarefaction was prevented. Regarding metabolic properties, immunoblotting and enzymatic assay raised beneficial effects of exercise on fatty acid transport and oxidation pathways. The correlation assessment indicated a positive correlation between variables of angiogenesis and FA utilisation, as well as between metabolism and echocardiographic parameters. In conclusion, early exercise improves exercise tolerance and attenuates cardiac structural and functional remodelling. In parallel, exercise attenuated myocardial capillary and lipid metabolism derangement in rats with aortic stenosis-induced heart failure.