RESUMO
The major risk factors to fatal outcome in COVID-19 patients, i.e., elderliness and pre-existing metabolic and cardiovascular diseases (CVD), share in common the characteristic of being chronic degenerative diseases of inflammatory nature associated with defective heat shock response (HSR). The molecular components of the HSR, the principal metabolic pathway leading to the physiological resolution of inflammation, is an anti-inflammatory biochemical pathway that involves molecular chaperones of the heat shock protein (HSP) family during homeostasis-threatening stressful situations (e.g., thermal, oxidative and metabolic stresses). The entry of SARS coronaviruses in target cells, on the other hand, aggravates the already-jeopardized HSR of this specific group of patients. In addition, cellular counterattack against virus involves interferon (IFN)-mediated inflammatory responses. Therefore, individuals with impaired HSR cannot resolve virus-induced inflammatory burst physiologically, being susceptible to exacerbated forms of inflammation, which leads to a fatal "cytokine storm". Interestingly, some species of bats that are natural reservoirs of zoonotic viruses, including SARS-CoV-2, possess an IFN-based antiviral inflammatory response perpetually activated but do not show any sign of disease or cytokine storm. This is possible because bats present a constitutive HSR that is by far (hundreds of times) more intense and rapid than that of human, being associated with a high core temperature. Similarly in humans, fever is a physiological inducer of HSR while antipyretics, which block the initial phase of inflammation, impair the resolution phase of inflammation through the HSR. These findings offer a rationale for the reevaluation of patient care and fever reduction in SARS, including COVID-19.
Assuntos
Betacoronavirus/fisiologia , Quirópteros/imunologia , Infecções por Coronavirus/imunologia , Resposta ao Choque Térmico , Pneumonia Viral/imunologia , Animais , Betacoronavirus/genética , COVID-19 , Quirópteros/virologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/genética , Infecções por Coronavirus/fisiopatologia , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/imunologia , Humanos , Interferons/imunologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/genética , Pneumonia Viral/fisiopatologia , SARS-CoV-2RESUMO
PURPOSE OF REVIEW: Heat therapy, such as sauna and hot tub, has become an increasingly regular therapeutical practice around the world since several studies have shown benefits of heat therapy in metabolic and cardiovascular diseases. The use of heat therapy in people with type 2 diabetes mellitus revealed a striking reduction of 1% unit in the glycated hemoglobin, suggesting this therapy for the treatment of diabetes. Herein, we shall discuss the use of heat therapy and the mechanisms involved, and suggest a provisional guide for the use of heat therapy in obesity and diabetes. RECENT FINDINGS: Human studies indicate that heat therapy reduces fasting glycemia, glycated hemoglobin, body weight, and adiposity. Animal studies have indicated that nitric oxide and the increase in heat shock protein 70 expression is involved in the improvements induced by heat therapy on insulin sensitivity, adiposity, inflammation, and vasomotricity. SUMMARY: Heat therapy is a promising and inexpensive tool for the treatment of obesity and diabetes. We proposed that transient increments in nitric oxide and heat shock protein 70 levels may explain the benefits of heat therapy. We suggest that heat therapy (sauna: 80-100°C; hot tub: at 40°C) for 15 min, three times a week, for 3 months, is a safe method to test its efficiency.
Assuntos
Diabetes Mellitus Tipo 2/terapia , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adiposidade , Animais , Glicemia/metabolismo , Peso Corporal , Modelos Animais de Doenças , Jejum , Regulação da Expressão Gênica , Hemoglobinas Glicadas/metabolismo , Temperatura Alta , Humanos , Resistência à Insulina , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Obesidade/terapia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Banho a Vapor/métodosRESUMO
Hot flashes, which involve a tiny rise in core temperature, are the most common complaint of peri- and post-menopausal women, being tightly related to decrease in estrogen levels. On the other hand, estradiol (E2) induces the expression of HSP72, a member of the 70 kDa family of heat shock proteins (HSP70), which are cytoprotective, cardioprotective, and heat inducible. Since HSP70 expression is compromised in age-related inflammatory diseases, we argued whether the capacity of triggering a robust heat shock (HS) response would be still present after E2 withdrawal. Hence, we studied the effects of HS treatment (hot tub) in female Wistar rats subjected to bilateral ovariectomy (OVX) after a 7-day washout period. Twelve h after HS, the animals were killed and aortic arches were surgically excised for molecular analyses. The results were compared with oxidative stress markers in the plasma (superoxide dismutase, catalase, and lipoperoxidation) because HSP70 expression is also sensitive to redox regulation. Extracellular (plasma) to intracellular HSP70 ratio, an index of systemic inflammatory status, was also investigated. The results showed that HS response was preserved in OVX animals, as inferred from HSP70 expression (up to 40% rise, p < 0.01) in the aortas, which was accompanied by no further alterations in oxidative stress, hematological parameters, and glycemic control either. This suggests that the lack of estrogen per se could not be solely ascribed as the unique source of low HSP70 expression as observed in long-term post-menopausal individuals. As a consequence, periodic evaluation of HSP70 status (iHSP70 vs. eHSP70) may be of clinical relevance because decreased HS response capacity is at the center of the onset of menopause-related dysfunctions.
Assuntos
Biomarcadores/metabolismo , Estrogênios/deficiência , Resposta ao Choque Térmico , Estresse Oxidativo , Animais , Aorta/metabolismo , Feminino , Proteínas de Choque Térmico HSP70/metabolismo , Temperatura Alta , Ovariectomia , RatosRESUMO
The inducible expression of the 70-kDa heat shock proteins (HSP70) is associated with homeostatically stressful situations. Stresses involving sympathetic nervous system (SNS) activation, including α1-adrenergic agonists and physical exercise, are capable of inducing HSP70 expression and release of the HSP70 inducible form, HSP72. However, whether hypoglycaemia is capable of influencing HSP70 status under a stressful situation such as insulin-induced hypoglycaemia (IIH), which also involves SNS activation, is unsettled. Hence, we decided to investigate whether the predominant signal for HSP70 expression and delivery into the blood comes from either low glucose, high insulin, or both during short-term IIH (STIIH) and long-term IIH (LTIIH). Our data indicated that low glucose level (up to 1.56 ± 0.14 mM), but not insulin, is the triggering factor responsible for a dramatic rise in HSP72 plasma concentrations (from 0.15 ± 0.01 in fed state to 0.77 ± 0.13 ng/mL during hypoglycaemic episodes). This was observed in parallel with up to 7-fold increases in interleukin-6 (IL-6) but not interleukin-10 (IL-10) or tumour necrosis factor-α (TNF-α) at STIIH. Together, the observations may suggest that HSP72 is released under hypoglycaemic conditions as a part of the homeostatic stress response, whereas at long-term, both hypoglycaemia and insulin may influence HSP72 expression in the liver, but not in kidneys. Secreted extracellular HSP72 (eHSP72) may be purely a danger signal to all the tissues of the body for the enhancement of immune and metabolic surveillance state or actively participates in glycaemic control under stressful situations.
Assuntos
Proteínas de Choque Térmico HSP72/sangue , Hipoglicemia/sangue , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Interleucina-10/sangue , Interleucina-6/sangue , Fígado/metabolismo , Fator de Necrose Tumoral alfa/sangue , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Glyphosate-based herbicides (GBHs) are the most worldwide used pesticides. The wide application of GBHs contaminates the soil and, consequently, water and food resources reaching human consumption. GBHs induce oxidative stress in non-target organisms, leading to a pro-inflammatory and pro-apoptotic cellular status, promoting tissue dysfunction and, thus, metabolic and neurobehavioral changes. This review presents evidence of oxidative damage induced by GBHs and the mechanism of cell damage and health consequences. To summarize, exposure to GBHs may induce disorders in calcium homeostasis related to the activation of ion channels. Also, alterations in pathways related to redox state regulation must have a primordial role in oxidative stress caused by GBHs.
Assuntos
Cálcio , Herbicidas , Humanos , Herbicidas/toxicidade , Estresse Oxidativo , Homeostase , GlifosatoRESUMO
Obesity and particulate air pollutant (PM2.5) are important risk factors for cardiometabolic diseases. PM2.5 exacerbates insulin resistance and lipid ectopic deposition in obese animals. The inorganic fraction of PM2.5, the Residual Oil Fly Ash (ROFA), is related to cardiovascular events, by enhancing the generation of reactive species, inflammatory cytokines, and leukocyte activation. However, the synergistic effects of ROFA and a high-fat diet (HFD) are still poorly described, and the studies were mainly conducted with males. AIMS: To investigate if ROFA could potentiate the cardiometabolic effects of diet-induced obesity in female rats. MATERIAL AND METHODS: Wistar female rats were divided into four groups: Control (n = 6), Polluted (n = 6), HFD (n = 6), and HFD + Polluted (n = 6). HFD and HFD + Polluted received a high-fat diet (HFD) (58.3 % as fats), whilst Control and Polluted groups received a standard diet (Nuvilab CR-1). In addition, Polluted and HFD + Polluted groups received intranasal instillation of ROFA (250 µg/50 µL), while Control and HFD groups received saline solution (50 µL) daily, five days per week. Both interventions occurred 24 weeks after the animals were euthanized. KEY FINDINGS: HFD combined with ROFA exposure impaired lipid profile challenged systemic and cardiac antioxidant defense, and presented a synergistic effect in inducing an immune-inflammatory condition. We found that the lipid profile disturbance is associated with HFD-induced hepatic, but not cardiac, deposition of triglycerides in female animals. SIGNIFICANCE: Our results support the hypothesis that ROFA exposure combined with bad feeding can exacerbate metabolic and cardiovascular diseases.
Assuntos
Poluição do Ar , Doenças Cardiovasculares , Masculino , Ratos , Feminino , Animais , Estresse Oxidativo , Ratos Wistar , Poluição do Ar/efeitos adversos , Cinza de Carvão/farmacologia , Obesidade , Lipídeos/farmacologia , Dieta Hiperlipídica/efeitos adversos , Material ParticuladoRESUMO
Obesity and exposure to fine particulate matter (PM2.5) are risk factors for insulin resistance, to which physical exercise is the most powerful non-pharmacological strategy. However, public concern over whether exercise could be protective in a polluted environment exists. Therefore, evaluating the possible benefits of exercise in polluted conditions in different contexts (age, gender, and cardiometabolic health) is imperative. In this sense, muscle plays a major role in maintaining glucose homeostasis, and its oxidative status is closely affected during exercise. This study tested whether moderate aerobic training could alleviate the metabolic and oxidative impairment in the gastrocnemius induced by the combination of a high-fat diet (HFD) and PM2.5 exposure. Female mice (B6129SF2/J) received HFD (58.3% of fat) or standard diet, intranasal instillation of 20 µg residual oil fly ash (ROFA: inorganic portion of PM2.5), or saline seven times per week for 19 weeks. In the 13th week, animals were submitted to moderate training or remained sedentary. Trained animals followed a progressive protocol for 6 weeks, ending at swimming with 5% body weight of workload for 60 min, while sedentary animals remained in shallow water. Aerobic moderate training attenuated weight gain and glucose intolerance and prevented muscle and pancreatic mass loss induced by a HFD plus ROFA exposure. Interestingly, a HFD combined with ROFA enhanced the catalase antioxidant activity, regardless of physical exercise. Therefore, our study highlights that, even in polluted conditions, moderate training is the most powerful non-pharmacological treatment for obesity and insulin resistance.
Assuntos
Poluição do Ar , Intolerância à Glucose , Resistência à Insulina , Camundongos , Feminino , Animais , Dieta Hiperlipídica/efeitos adversos , Obesidade , Antioxidantes , Material Particulado , Camundongos Endogâmicos C57BLRESUMO
The 70-kDa heat shock proteins (HSP70) may provide relevant information about the endothelial dysfunction in cardiovascular diseases. Located in the intracellular milieu (iHSP70), they are essential chaperones that inhibit nuclear factor kappa B activation, stimulate nitric oxide production and superoxide dismutase activity, and inhibit apoptosis. However, under stressful conditions, HSP70 can be released into the extracellular medium (eHSP70) and act as an inflammatory mediator. Although studies have reported the vasoprotective role of iHSP70, the evidence regarding eHSP70 is contradictory. eHSP70 can activate NFκB and activator protein-1, thus stimulating the release of inflammatory cytokines and production of reactive oxygen species. Due to the antagonistic nature of HSP70 according to its location, the eHSP70/iHSP70 ratio (Heck index) has been proposed as a better marker of inflammatory status; however, more studies are required to confirm this hypothesis. Therefore, this review summarises studies that, together, describe the role of HSP70 in endothelial dysfunction.
Assuntos
Aterosclerose , Proteínas de Choque Térmico HSP70 , Biomarcadores , Citocinas , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , NF-kappa B/metabolismoRESUMO
The Murine Sepsis Score (MSS) is used to assess the severity of sepsis in rats and mice based on observational characteristics. The quantitative variables of glycemia, body weight, and temperature are predictors of severity in experimental models of sepsis. Therefore, our study sought to adapt the MSS with the same variables to indicate earlier the severity of the disease in murine models of the disease. Sepsis mice presented hypoglycemia, weight loss, and hypothermia. Therefore, these variables were included in the Adapted Murine Sepsis Score (A-MSS). The A-MASS presented 100% specificity and 87.5% sensibility been able to differentiate the early sepsis symptoms and its severity. The A-MSS allows an early and more complete diagnosis of sepsis in mice and might be considered as a procedure to improve the analysis of systemic sepsis dysfunction in murine experimental models.
Assuntos
Hipotermia , Sepse , Animais , Peso Corporal , Modelos Animais de Doenças , Camundongos , Modelos Teóricos , Ratos , Sepse/diagnósticoRESUMO
Decreased estrogen levels in menopause are associated with anthropometric, metabolic, and inflammatory impairments, predisposing women to cardiometabolic risk factors such as diabetes. Menopause and type two diabetes (DM2) are marked by altered heat shock response (HSR), shown by decreased expression of the 70-kDa heat shock protein in the intracellular milieu (iHSP70). While iHSP70 plays an anti-inflammatory role, extracellular HSP70 (eHSP70) may mediate pro-inflammatory pathways and has been associated with insulin resistance in DM2. Considering the roles of these proteins according to localization, the eHSP70-to-iHSP70 ratio (H-index) has been proposed as a biomarker for HSR. We, therefore, evaluated whether this biomarker is associated with glycemic and inflammatory status in postmenopausal women. In this transversal study, 36 postmenopausal women were grouped according to fasting glycemia status as either the control group (normoglycemic, ≤ 99 mg/dL) or DM2 (prediabetic and diabetic, glycemia ≥ 100 mg/dL). DM2 group showed higher triglyceride/glucose (TyG) index and plasma atherogenic index (PAI), both of which are indicators of cardiometabolic risk. In addition, we found that the eHSP70-to-iHSP70 ratio (plasma/peripheral blood mononuclear cells-PBMC ratio) was higher in the DM2 group, compared with the control group. Furthermore, blood leukocyte and glycemia levels were positively correlated with the eHSP70-to-iHSP70 ratio in women that presented H-index values above 1.0 (a.u.). Taken together, our results highlight the eHSP70-to-iHSP70 ratio as a biomarker of altered HSR in DM2 postmenopausal women.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Proteínas de Choque Térmico HSP70 , Pós-Menopausa , Estado Pré-Diabético , Biomarcadores/metabolismo , Glicemia , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Estrogênios , Feminino , Proteínas de Choque Térmico HSP110/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Estado Pré-Diabético/complicações , Estado Pré-Diabético/metabolismo , TriglicerídeosRESUMO
Physical exercise has acute and chronic effects on inflammatory balance, metabolic regulation, and redox status. Exercise-induced adaptations are mediated by enhanced 70-kDa heat shock protein (HSP70) levels and an improved heat shock response (HSR). Therefore, exercise could be useful against disease conditions [obesity, diabetes mellitus (DM), and exposure to atmospheric pollutants] marked by an impaired HSR. However, exercise performed by obese or diabetic subjects under pollution conditions might also be dangerous at certain intensities. Intensity correlates with an increase in HSP70 levels during physical exercise until a critical point at which the effort becomes harmful and impairs the HSR. Establishing a unique biomarker able to indicate the exercise intensity on metabolism and cellular fatigue is essential to ensure adequate and safe exercise recommendations for individuals with obesity or DM who require exercise to improve their metabolic status and live in polluted regions. In this review, we examined the available evidence supporting our hypothesis that HSP70 could serve as a biomarker for determining the optimal exercise intensity for subjects with obesity or diabetes when exposed to air pollution and establishing the fine threshold between anti-inflammatory and pro-inflammatory exercise effects.
Assuntos
Poluição do Ar/efeitos adversos , Exercício Físico/efeitos adversos , Proteínas de Choque Térmico HSP70/sangue , Inflamação/sangue , Biomarcadores/sangue , Complicações do Diabetes/sangue , Complicações do Diabetes/complicações , Complicações do Diabetes/terapia , Resposta ao Choque Térmico/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Obesidade/sangue , Obesidade/complicações , Obesidade/terapia , Estresse Oxidativo/efeitos dos fármacosRESUMO
Women live approximately one-third of their lives in postmenopause. Among postmenopausal women, type 2 diabetes mellitus (DM2) is one of the most prevalent chronic diseases. These conditions promote alterations in the oxidative, metabolic, and immune-inflammatory profiles marked by higher extracellular 72 kDa-heat shock protein (eHSP72). Here, we investigated whether the time of menopause is associated with oxidative cellular stress marker levels in postmenopausal women with DM2. Sixty-four women were recruited (56.7 ± 12.6 years old) in the pre- (n = 22) and postmenopause (n = 42) period, with (n = 19) or without DM2 (n = 45), and a fasting blood collection was made for the evaluation of metabolic, oxidative, and inflammatory markers. We found that menopause and DM2 influenced metabolic and oxidative parameters and presented synergistic effects on the plasma lipoperoxidation levels. Also, postmenopausal women had the highest eHSP72 concentration levels associated with the years in postmenopause. We conclude that the time of menopause impacts the markers of cellular stress and increases the risk of oxidative stress, mainly when it is associated with DM2.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Proteínas de Choque Térmico HSP72/sangue , Estresse Oxidativo , Pós-Menopausa/sangue , Adulto , Idoso , Brasil , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Fine particulate matter (PM2.5) has been considered a risk factor for cardiovascular diseases by inducing an oxidative and inflammatory phenotype. Besides, the reduction of 17ß-estradiol (E2) levels during menopause is a natural risk for cardiovascular outcomes. During the E2 downfall, there is a high requirement of the 70-kDa heat shock proteins (HSP70), which present essential antioxidant, anti-inflammatory, and anti-senescence roles. We investigated if the ovariectomy, an animal model for menopause, could induce additional effects in cardiac health by impairing oxidative and heat shock response parameters of female rats chronically exposed to residual oil fly ash (ROFA; an inorganic fraction of PM2.5). Thus, ROFA was obtained from São Paulo (Brazil) and solubilized it in saline. Further, female Wistar rats were exposed to 50 µL of saline (control group) or ROFA solution (250 µg) (polluted) by intranasal instillation, 5 days/week, 12 weeks. At the 12th week, animals were subdivided into four groups (n = 6 p/group): control, OVX, polluted, and polluted + OVX. Control and polluted were submitted to false surgery, while OVX and polluted + OVX were ovariectomized. ROFA or saline exposure continued for 12 weeks. Ovariectomy reduced the cardiac catalase activity and iHSP70 expression in female rats exposed to ROFA. Neither plasma eHSP72 levels nor H-index (eHSP72 to cardiac iHSP70 ratio) was affected. In conclusion, ovariectomy reduces the cardiac cytoprotection and antioxidant defense, and enhances the susceptibility to premature cellular senescence in rats exposed to ROFA.
Assuntos
Poluentes Atmosféricos , Animais , Brasil , Cinza de Carvão , Citoproteção , Feminino , Humanos , Ovariectomia , Estresse Oxidativo , Material Particulado , Ratos , Ratos WistarRESUMO
The coronavirus disease that emerged in 2019 (COVID-19) is highly contagious and has given way to a global pandemic. A present COVID-19 has high transmission rates worldwide, including in small Brazilian cities such as Ijuí. Located in the northwest part of the state of Rio Grande do Sul (RS) and with a population of 83,475, Ijuí was selected as the site of a population-based survey involving 2,222 subjects, from April to June 2020. Subjects were tested for the presence of antibodies against coronavirus (SARS-CoV-2) and answered questions regarding social distance adherence (SDA), daily preventive routines (DPR), comorbidities, and sociodemographic characteristics. In parallel, the local government registered the official COVID-19 cases in Ijuí, as well as the mobile social distancing index (MSDI). In this study, we demonstrate that there was a decrease in the levels of SDA, DPR and MSDI before the beginning of COVID-19 community transmission in Ijuí. Furthermore, we provide predictions for the number of COVID-19 cases, hospitalizations, and deaths in the city. We conclude that insufficient social distancing, as evidenced by different methods, may be related to the rapid increase of COVID-19 cases in Ijuí. Our study predicts an approaching outbreak of COVID-19 in Ijuí through community spread, which could be avoided or attenuated with increased levels of social distancing among the population.
Assuntos
COVID-19/transmissão , Pandemias/prevenção & controle , Distanciamento Físico , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude , Atitude Frente a Saúde , Brasil/epidemiologia , COVID-19/prevenção & controle , COVID-19/virologia , Cidades/epidemiologia , Transmissão de Doença Infecciosa/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quarentena/psicologia , SARS-CoV-2/isolamento & purificação , Inquéritos e Questionários , Adulto JovemRESUMO
Obesity and exposure to fine particulate matter (air pollutant PM2.5) are important risk factors for metabolic and cardiovascular diseases. They are also related to early menopause. The reduction of 17ß-estradiol (E2) levels during female climacteric, marked by menopause, is of significant concern because of its imminent influence on metabolism, redox and inflammatory status. This complex homeostasis-threatening scenario may induce a heat shock response (HSR) in cells, enhancing the expression of the 70 kDa heat shock protein (HSP70). A failure in this mechanism could predispose women to cardiovascular diseases. In this study, we evaluated if the climacteric could represent an additional risk among obese rats exposed to PM2.5 by worsening lipid, oxidative, and inflammatory parameters and HSP70 in cardiac tissue. We induced obesity in female Wistar rats using a high-fat diet (HFD) (58.3% as fats) and exposed them to 50 µL of saline 0.9% (control, n = 15) or 250 µg residual oil fly ash (ROFA, the inorganic portion of PM2.5) (polluted, n = 15) by intranasal instillation, 5 days/w for 12 weeks. At the 12th week, we subdivided these animals into four groups: control (n = 6), OVX (n = 9), polluted (n = 6) and polluted + OVX (n = 9). OVX and polluted + OVX were submitted to a bilateral ovariectomy (OVX), a surgical model for menopause, while control and polluted received a false surgery (sham). ROFA exposure and HFD consumption were continued for 12 additional weeks, after which the animals were euthanized. ROFA enhanced the susceptibility to ovariectomy-induced dyslipidemia, while ovariectomy predisposed female rats to the ROFA-induced decrease of cardiac iHSP70 expression. Ovariectomy also decreased the IL-6 levels and IL-6/IL-10 in obese animals, reinforcing a metabolic impairment and a failure to respond to unfavorable conditions. Our results support the hypothesis that obese ovariectomized animals are predisposed to a metabolic worsening under polluted conditions and are at higher risk of cardiovascular diseases.
Assuntos
Dieta Hiperlipídica , Material Particulado , Animais , Dieta Hiperlipídica/efeitos adversos , Feminino , Resposta ao Choque Térmico , Humanos , Ovariectomia , Oxirredução , Estresse Oxidativo , Material Particulado/toxicidade , Ratos , Ratos WistarRESUMO
Sepsis is a systemic infection that causes multiple organ dysfunction. HSP70 is a protein responsive to cell stress, in particular oxidative stress. Therefore, this literature review sought to investigate the roles of HSP70 and oxidative stress in the pathophysiology of sepsis and the possibility of HSP70 as a therapeutic target. HSP70 exerts a protective effect when located in cells (iHSP70), and its decrease, as well as its increase in the extracellular environment (eHSP70), under oxidative stress is a biomarker of sepsis severity. In addition, therapies that increase iHSP70 and treatment with HSP70 promote sepsis improvement.
A sepse é uma infecção sistêmica que acarreta disfunção múltipla dos órgãos. A HSP70 é uma proteína responsiva ao estresse celular, assim como o estresse oxidativo. Esta revisão da literatura buscou investigar a HSP70 e o estresse oxidativo quanto à fisiopatologia da sepse e ao papel da HSP70 como possível alvo terapêutico. A HSP70 exerce efeito protetor quando localizada na célula (iHSP70), e sua diminuição, assim como seu aumento no ambiente extracelular (eHSP70) e o estresse oxidativo, é um biomarcador de gravidade na sepse. Além disso, terapias que aumentam a iHSP70 ou o próprio tratamento com HSP70 promovem a melhora na sepse.
Assuntos
Proteínas de Choque Térmico HSP70 , Sepse , Biomarcadores/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Estresse OxidativoRESUMO
INTRODUCTION: The 72kDa heat shock protein, HSP72, located intracellularly provides cochlear cytoprotective and anti-inflammatory roles in the inner ear during stressful noise challenges. The expression of intracellular HSP72 (iHSP72) can be potentiated by alanyl-glutamine dipeptide supplementation. Conversely, these proteins act as pro-inflammatory signals in the extracellular milieu (eHSP72). OBJECTIVE: We explore whether noise-induced hearing loss promotes both intracellular and extracellular HSP72 heat shock response alterations, and if alanyl-glutamine dipeptide supplementation could modify heat shock response and prevent hearing loss. METHODS: Female 90 day-old Wistar rats (n=32) were randomly divided into four groups: control, noise-induced hearing loss, treated with alanyl-glutamine dipeptide and noise-induced hearing loss plus alanyl-glutamine dipeptide. Auditory brainstem responses were evaluated before noise exposure (124dB SPL for 2h) and 14days after. Cochlea, nuclear cochlear complex and plasma samples were collected for the measurement of intracellular HSP72 and extracellular HSP72 by a high-sensitivity ELISA kit. RESULTS: We found an increase in both iHSP72 and eHSP72 levels in the noise-induced hearing loss group, which was alleviated by alanyl-glutamine dipeptide treatment. Furthermore, H-index of HSP72 (plasma/cochlea eHSP72/iHSP72 ratio) was increased in the noise-induced hearing loss group, but prevented by alanyl-glutamine dipeptide treatment, although alanyl-glutamine dipeptide had no effect on auditory threshold. CONCLUSIONS: Our data indicates that cochlear damage induced by noise exposure is accompanied by local and systemic heat shock response markers. Also, alanyl-glutamine reduced stress markers even though it had no effect on noise-induced hearing loss. Finally, plasma levels of 72kDa heat shock proteins can be used as a biomarker of auditory stress after noise exposure.
Assuntos
Perda Auditiva Provocada por Ruído , Animais , Suplementos Nutricionais , Dipeptídeos , Feminino , Perda Auditiva Provocada por Ruído/tratamento farmacológico , Perda Auditiva Provocada por Ruído/prevenção & controle , Proteínas de Choque Térmico , Resposta ao Choque Térmico , Ratos , Ratos WistarRESUMO
High levels of extracellular 72 kDa heat shock protein (eHSP72) can be detected in the serum of septic patients and are associated with increased oxidative profiles and elevated rates of mortality among these patients. However, a possible immunomodulatory role for this protein, resulting in tissue protection during sepsis, has never been assessed. In this study, we investigated whether eHSP72 administration could attenuate the severity of sepsis in a mouse peritonitis model. Animals (90-day-old male C57BL/6J mice) were divided into Sepsis (n = 8) and Sepsis + eHSP72 (n = 9) groups, which both received injections of 20% fecal solution [1 mg/g body weight (wt), intraperitoneal (i.p.)], to trigger peritonitis induced-sepsis, whereas a Control group (n = 7) received a saline injection. eHSP72 was administered (1.33 ng/g body wt) to the Sepsis+eHSP72 group, 12 h after sepsis induction. All animals were evaluated for murine sepsis score (MSS), hemogram, core temperature, and glycemia (before and 4, 12, and 24 h after sepsis induction). Treatment with eHSP72 promoted reduced sepsis severity 24 h after sepsis induction, based on MSS scores (Control = 1.14 ± 1.02; Sepsis = 11.07 ± 7.24, and Sepsis + eHSP72 = 5.62 ± 1.72, P < 0.001) and core temperatures (°C; Control = 37.48 ± 0.58; Sepsis = 35.17 ± 2.88, and Sepsis + eHSP72 = 36.94 ± 2.02; P = 0.006). eHSP72 treatment also limited the oxidative profile and respiratory dysfunction in mice with sepsis. Although sepsis modified glycemic levels and white and red blood cell counts, these variables were not influenced by eHSP72 treatment (P > 0.05). Finally, eHSP72 improved the survival rate after sepsis (P = 0.0371). Together, our results indicated that eHSP72 may ameliorate sepsis severity and possibly improve some sepsis indices in mice.
Assuntos
Proteínas de Choque Térmico HSP72/administração & dosagem , Peritonite/terapia , Sepse/terapia , Animais , Modelos Animais de Doenças , Imunomodulação , Infusões Intravenosas , Masculino , Camundongos Endogâmicos C57BL , Peritonite/imunologia , Sepse/imunologiaRESUMO
The subchronic exposure to fine particulate matter (PM2.5) and high-fat diet (HFD) consumption lead to glucose intolerance by different mechanisms involving oxidative stress and inflammation. Under stressful conditions, the cells exert a heat shock response (HSR), by releasing the 72-kDa heat shock proteins (eHSP72), fundamental chaperones. The depletion of the HSR can exacerbate the chronic inflammation. However, there are few studies about the early effects of the association of HFD consumption and exposure to low concentrations of PM2.5 in the oxidative stress and HSR, in the genesis of glucose intolerance. Thus, we divided 23 male B6129SF2/J mice into control (n = 6), polluted (n = 6), HFD (n = 6), and high-fat diet + polluted (HFD + polluted) (n = 5) groups. Control and polluted received a standard diet (11.4% of fats), while HFD and HFD + polluted received HFD (58.3% of fats). Simultaneously, polluted and HFD + polluted received 5 µg/10 µL of PM2.5, daily, 7×/week, while control and HFD were exposed to 10 µL of saline solution 0.9% for 12 weeks. At the 12th week, animals were euthanized. We collected the metabolic tissues to analyze oxidative parameters, total blood to the hematological parameters, and plasma to eHSP72 measurement. The association of HFD and PM2.5 impaired glucose tolerance in the 12th week. Besides, it triggered an antioxidant defense by the adipose tissue, which was negatively correlated with eHSP72 levels. In conclusion, a low concentration of PM2.5 exposure associated with HFD consumption leads to glucose intolerance, by impairing adipose tissue antioxidant defense and systemic eHSP72 levels.
Assuntos
Intolerância à Glucose , Resistência à Insulina , Tecido Adiposo , Animais , Antioxidantes , Dieta Hiperlipídica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Material ParticuladoRESUMO
Low estrogen levels may predispose women to increased bodyweight and dyslipidemia. Previous studies from our laboratory suggest an involvement of depressed heat shock response (HSR) in this scenario because estrogen potently stimulates HSR. As heat treatment induces the expression of the anti-inflammatory heat shock proteins of the 70-kDa family (HSP70) and its accompanying HSR, we aimed to investigate whether chronic heat treatment promotes beneficial effects on biometric, lipid profile, oxidative stress, and HSR in ovariectomized rats. Wistar adult female rats (n = 32) were divided into four groups: control (C, n = 7), ovariectomized (OVX, n = 9), heat-treated (HT, n = 9), and heat-treated ovariectomized rats (OVX+HT, n = 7). HT and OVX+HT rats were anesthetized and submitted to heat treatment (once a week for 12 weeks) in a water bath (41 °C) to increase rats' rectal temperature up to 41 °C for 15 min, while C and OVX animals were submitted to a 36 °C water bath. HT attenuated the weight gain induced by OVX and increased HDL cholesterol and triglyceride serum levels. Also, OVX rats showed increased total cholesterol and LDL cholesterol levels that were not influenced by HT. Interestingly, it was found that an overall trend for HT to decrease tissue catalase and superoxide dismutase antioxidant activities was paralleled by a decrease in malondialdehyde levels (indicative of lower lipoperoxidation), especially in the skeletal muscle. Surprisingly, OVX was not able to depress intracellular HSP70 expression in the skeletal muscle, as expected, and this remained unchanged with HT. However, chronic HT did enhance intracellular HSP70 contents in white adipose tissue of OVX animals. As both glucose and insulin tolerance tests were not affected by OVX, which was not modified by HT, we suppose that estrogen absence alone is not sufficient to determine a state of insulin resistance associated with low intramuscular HSP70 content.