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Article ; Online: Oxidative stress and decreased tissue HSP70 are involved in the genesis of sepsis: HSP70 as a therapeutic target.

Sulzbacher, Maicon Machado / Ludwig, Mirna Stela / Heck, Thiago Gomes

2020 Volume 32, Issue 4, Page(s) 585–591

Abstract: 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 ... ...

Title translation	Estresse oxidativo e diminuição de HSP70 tecidual envolvidos na gênese da sepse: HSP70 como alvo terapêutico.
Abstract	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.
MeSH term(s)	Biomarkers/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; Humans ; Oxidative Stress ; Sepsis
Chemical Substances	Biomarkers ; HSP70 Heat-Shock Proteins
Language	English
Publishing date	2020-12-03
Publishing country	Brazil
Document type	Journal Article ; Review
ZDB-ID	2732162-9
ISSN	1982-4335 ; 0103-507X
ISSN (online)	1982-4335
ISSN	0103-507X
DOI	10.5935/0103-507X.20200084
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Article ; Online: Moderate aerobic training is safe and improves glucose intolerance induced by the association of high fat diet and air pollution

dos Santos, Analú Bender / Costa-Beber, Lílian Corrêa / de Pelegrin Basso, Eloisa Gabriela / Donato, Yohanna Hannah / Sulzbacher, Maicon Machado / Sulzbacher, Lucas Machado / Ludwig, Mirna Stela / Heck, Thiago Gomes

Environ Sci Pollut Res. 2023 Jan., v. 30, no. 1 p.1908-1918

2023

Abstract: 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 ...

Abstract	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.
Keywords	air pollution ; antioxidant activity ; catalase ; exercise ; females ; fly ash ; glucose ; high fat diet ; homeostasis ; insulin resistance ; muscles ; obesity ; oils ; particulates ; risk ; weight gain
Language	English
Dates of publication	2023-01
Size	p. 1908-1918.
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	1178791-0
ISSN	1614-7499 ; 0944-1344
ISSN (online)	1614-7499
ISSN	0944-1344
DOI	10.1007/s11356-022-22196-5
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Article ; Online: Increased eHSP70-to-iHSP70 ratio in prediabetic and diabetic postmenopausal women: a biomarker of cardiometabolic risk.

Seibert, Priscila / Anklam, Carolain Felipin Vincensi / Costa-Beber, Lílian Corrêa / Sulzbacher, Lucas Machado / Sulzbacher, Maicon Machado / Sangiovo, Angela Maria Blanke / Dos Santos, Fernanda Knopp / Goettems-Fiorin, Pauline Brendler / Heck, Thiago Gomes / Frizzo, Matias Nunes / Ludwig, Mirna Stela

Cell stress & chaperones

2022 Volume 27, Issue 5, Page(s) 523–534

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Biomarkers/metabolism ; Blood Glucose ; Cardiovascular Diseases/diagnosis ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/metabolism ; Estrogens ; Female ; HSP110 Heat-Shock Proteins/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; Humans ; Leukocytes, Mononuclear/metabolism ; Postmenopause ; Prediabetic State/complications ; Prediabetic State/metabolism ; Triglycerides
Chemical Substances	Biomarkers ; Blood Glucose ; Estrogens ; HSP110 Heat-Shock Proteins ; HSP70 Heat-Shock Proteins ; HSPA4 protein, human ; Triglycerides
Language	English
Publishing date	2022-06-29
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1362749-1
ISSN	1466-1268 ; 1355-8145
ISSN (online)	1466-1268
ISSN	1355-8145
DOI	10.1007/s12192-022-01288-8
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Article ; Online: Moderate aerobic training is safe and improves glucose intolerance induced by the association of high fat diet and air pollution.

Dos Santos, Analú Bender / Costa-Beber, Lílian Corrêa / de Pelegrin Basso, Eloisa Gabriela / Donato, Yohanna Hannah / Sulzbacher, Maicon Machado / Sulzbacher, Lucas Machado / Ludwig, Mirna Stela / Heck, Thiago Gomes

Environmental science and pollution research international

2022

Abstract: Obesity and exposure to fine particulate matter ( ... ...

Abstract	Obesity and exposure to fine particulate matter (PM
Language	English
Publishing date	2022-08-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1178791-0
ISSN	1614-7499 ; 0944-1344
ISSN (online)	1614-7499
ISSN	0944-1344
DOI	10.1007/s11356-022-22196-5
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Article ; Online: Adapted Murine Sepsis Score: Improving the Research in Experimental Sepsis Mouse Model.

Sulzbacher, Maicon Machado / Sulzbacher, Lucas Machado / Passos, Felipe Rafael / Bilibio, Bruna Letícia Endl / de Oliveira, Kauana / Althaus, Wellington Felipe / Frizzo, Matias Nunes / Ludwig, Mirna Stela / Da Cruz, Ivana Beatrice Mânica / Heck, Thiago Gomes

BioMed research international

2022 Volume 2022, Page(s) 5700853

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Animals ; Body Weight ; Disease Models, Animal ; Hypothermia ; Mice ; Models, Theoretical ; Rats ; Sepsis/diagnosis
Language	English
Publishing date	2022-01-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2022/5700853
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Article ; Online: Effects of aerobic and resistance exercise training associated with carnosine precursor supplementation on maximal strength and V̇O

Stefani, Giuseppe Potrick / Capalonga, Lucas / da Silva, Lucas Ribeiro / Heck, Thiago Gomes / Frizzo, Matias Nunes / Sulzbacher, Lucas Machado / Sulzbacher, Maicon Machado / de Batista, Diovana / Vedovatto, Samlai / Bertoni, Ana Paula Santin / Wink, Márcia Rosângela / Dal Lago, Pedro

Life sciences

2021 Volume 282, Page(s) 119816

Abstract: Background: Combined exercise training (CET) has been associated with positive responses in the clinical status of patients with heart failure (HF). Other nonpharmacological tools, such as amino acid supplementation, may further enhance its adaptation. ... ...

Abstract	Background: Combined exercise training (CET) has been associated with positive responses in the clinical status of patients with heart failure (HF). Other nonpharmacological tools, such as amino acid supplementation, may further enhance its adaptation. The aim was to test whether CET associated with supplementing carnosine precursors could present better responses in the functional capacity and biochemical variables of rats with HF. Methods: Twenty-one male Wistar rats were subjected to myocardial infarction and allocated to three groups: sedentary (SED, n = 7), CET supplemented with placebo (CETP, n = 7), and CET with HF supplemented with β-alanine and L-histidine (CETS, n = 7). The trained animals were submitted to a strength protocol three times per week. Aerobic training was conducted twice per week. The supplemented group received β-alanine and L-histidine orally (250 mg/kg per day). Results: Maximum oxygen uptake, running distance, time to exhaustion and maximum strength were higher in the CET-P group than that in the SED group and even higher in the CET-S group than that in the CET-P group (P < 0.01). CET-S showed lower oxidative stress and inflammation markers and higher heat shock protein 72 kDa content and mRNA expression for calcium transporters in the skeletal muscle compared to SED. Conclusion: CET together with β-alanine and L-histidine supplementation in rats with HF can elicit adaptations in both maximum oxygen uptake, running distance, time to exhaustion, maximum strength, oxidative stress, inflammation and mRNA expression. Carnosine may influence beneficial adjustments in the cell stress response in the skeletal muscle and upregulate the mRNA expression of calcium transporters.
MeSH term(s)	Animals ; Carnosine/pharmacology ; Disease Models, Animal ; Heart Failure/blood ; Heart Failure/drug therapy ; Heart Failure/physiopathology ; Histidine/pharmacology ; Male ; Oxygen/blood ; Physical Conditioning, Animal ; Rats ; Rats, Wistar ; beta-Alanine/pharmacology
Chemical Substances	beta-Alanine (11P2JDE17B) ; Histidine (4QD397987E) ; Carnosine (8HO6PVN24W) ; Oxygen (S88TT14065)
Language	English
Publishing date	2021-07-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2021.119816
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Article: Effects of aerobic and resistance exercise training associated with carnosine precursor supplementation on maximal strength and [formula omitted]O2max in rats with heart failure

Life sciences. 2021 Oct. 01, v. 282

2021

Abstract: Combined exercise training (CET) has been associated with positive responses in the clinical status of patients with heart failure (HF). Other nonpharmacological tools, such as amino acid supplementation, may further enhance its adaptation. The aim was ... ...

Abstract	Combined exercise training (CET) has been associated with positive responses in the clinical status of patients with heart failure (HF). Other nonpharmacological tools, such as amino acid supplementation, may further enhance its adaptation. The aim was to test whether CET associated with supplementing carnosine precursors could present better responses in the functional capacity and biochemical variables of rats with HF. Twenty-one male Wistar rats were subjected to myocardial infarction and allocated to three groups: sedentary (SED, n = 7), CET supplemented with placebo (CETP, n = 7), and CET with HF supplemented with β-alanine and L-histidine (CETS, n = 7). The trained animals were submitted to a strength protocol three times per week. Aerobic training was conducted twice per week. The supplemented group received β-alanine and L-histidine orally (250 mg/kg per day). Maximum oxygen uptake, running distance, time to exhaustion and maximum strength were higher in the CET-P group than that in the SED group and even higher in the CET-S group than that in the CET-P group (P < 0.01). CET-S showed lower oxidative stress and inflammation markers and higher heat shock protein 72 kDa content and mRNA expression for calcium transporters in the skeletal muscle compared to SED. CET together with β-alanine and L-histidine supplementation in rats with HF can elicit adaptations in both maximum oxygen uptake, running distance, time to exhaustion, maximum strength, oxidative stress, inflammation and mRNA expression. Carnosine may influence beneficial adjustments in the cell stress response in the skeletal muscle and upregulate the mRNA expression of calcium transporters.
Keywords	calcium ; carnosine ; gene expression ; heart failure ; heat shock proteins ; histidine ; inflammation ; males ; myocardial infarction ; oxidative stress ; oxygen ; peak oxygen uptake ; placebos ; skeletal muscle ; strength training ; stress response
Language	English
Dates of publication	2021-1001
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2021.119816
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Article ; Online: A single dose of eHSP72 attenuates sepsis severity in mice.

Sulzbacher, Maicon Machado / Sulzbacher, Lucas Machado / Passos, Felipe Rafael / Bilibio, Bruna Letícia Endl / Althaus, Wellington Felipe / Weizenmann, Luana / de Oliveira, Kauana / Frizzo, Matias Nunes / Ludwig, Mirna Stela / Heck, Thiago Gomes

Scientific reports

2020 Volume 10, Issue 1, Page(s) 9198

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Animals ; Disease Models, Animal ; HSP72 Heat-Shock Proteins/administration & dosage ; Immunomodulation ; Infusions, Intravenous ; Male ; Mice, Inbred C57BL ; Peritonitis/immunology ; Peritonitis/therapy ; Sepsis/immunology ; Sepsis/therapy
Chemical Substances	HSP72 Heat-Shock Proteins
Language	English
Publishing date	2020-06-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-66011-y
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Article ; Online: Subacute exposure to residual oil fly ash (ROFA) increases eHSP70 content and extracellular-to-intracellular HSP70 ratio: a relation with oxidative stress markers.

Baldissera, Fernanda Giesel / Dos Santos, Analú Bender / Sulzbacher, Maicon Machado / Goettems-Fiorin, Pauline Brendler / Frizzo, Matias Nunes / Ludwig, Mirna Stela / Rhoden, Claudia Ramos / Heck, Thiago Gomes

Cell stress & chaperones

2018 Volume 23, Issue 6, Page(s) 1185–1192

Abstract: The purpose of this study was to evaluate whether exposure to particles induces an imbalance in 70-kDa heat shock proteins (HSP70). Since intracellularly (iHSP70) it has anti-inflammatory roles whereas extracellularly (eHSP70) it has pro-inflammatory ... ...

Abstract	The purpose of this study was to evaluate whether exposure to particles induces an imbalance in 70-kDa heat shock proteins (HSP70). Since intracellularly (iHSP70) it has anti-inflammatory roles whereas extracellularly (eHSP70) it has pro-inflammatory roles, we evaluate the effect of residual oil fly ash (ROFA) exposure on eHSP70-to-iHSP70 ratio (H index), a biomarker of inflammatory status that is related to oxidative stress in plasma and lymphoid tissue. Wistar rats that received ROFA suspension for three consecutive days (750 μg) showed an increase in plasma eHSP70 levels (mainly the 72-kDa inducible form). Also, ROFA promoted alterations on plasma oxidative stress (increased protein carbonyl groups and superoxide dismutase activity, and decrease sulfhydryl groups). There was an increase in H index of the plasma/thymus with no changes in circulating leukocyte level, iHSP70, or oxidative stress markers in lymphoid tissues. Our results support the hypothesis that eHSP70 content and H index represent inflammatory and oxidative biomarkers.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Coal Ash/toxicity ; Environmental Exposure ; HSP70 Heat-Shock Proteins/metabolism ; Leukocytes/cytology ; Leukocytes/metabolism ; Lymphoid Tissue/metabolism ; Male ; Oxidative Stress ; Rats ; Rats, Wistar
Chemical Substances	Biomarkers ; Coal Ash ; HSP70 Heat-Shock Proteins
Language	English
Publishing date	2018-06-22
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1362749-1
ISSN	1466-1268 ; 1355-8145
ISSN (online)	1466-1268
ISSN	1355-8145
DOI	10.1007/s12192-018-0924-z
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