RESUMO
Here we have shown for the first time altered expression of the vascular smooth muscle (VSM) KATP channel subunits in segments of the human internal mammary artery (HIMA) in patients with type-2 diabetes mellitus (T2DM). Functional properties of vascular KATP channels in the presence of T2DM, and the interaction between its subunits and endogenous ligands known to relax this vessel, were tested using the potassium (K) channels opener, pinacidil. HIMA is the most commonly used vascular graft in cardiac surgery. Previously it was shown that pinacidil relaxes HIMA segments through interaction with KATP (SUR2B/Kir6.1) vascular channels, but it is unknown whether pinacidil sensitivity is changed in the presence of T2DM, considering diabetes-induced vascular complications commonly seen in patients undergoing coronary artery bypass graft surgery (CABG). KATP subunits were detected in HIMA segments using Western blot and immunohistochemistry analyses. An organ bath system was used to interrogate endothelium-independent vasorelaxation caused by pinacidil. In pharmacological experiments, pinacidil was able to relax HIMA from patients with T2DM, with sensitivity comparable to our previous results. All three KATP subunits (SUR2B, Kir6.1 and Kir6.2) were observed in HIMA from patients with and without T2DM. There were no differences in the expression of the SUR2B subunit. The expression of the Kir6.1 subunit was lower in HIMA from T2DM patients. In the same group, the expression of the Kir6.2 subunit was higher. Therefore, KATP channels might not be the only method of pinacidil-induced dilatation of T2DM HIMA. T2DM may decrease the level of Kir6.1, a dominant subunit in VSM of HIMA, altering the interaction between pinacidil and those channels.
RESUMO
The aims of this study were to examine the effects of pyridoxine administration on the activities of cardiac antioxidant stress enzymes superoxide dismutase (SOD) and catalase (CAT) and enzyme indicators of cardiometabolic status, lactate and malate dehydrogenase (LDH, MDH), as well as LDH and MDH isoforms' distribution in the cardiac tissue of healthy and diabetic Wistar male rats. Experimental animals were divided into five groups: C1-control (0.9% sodium chloride-NaCl-1 mL/kg, intraperitoneally (i.p.), 1 day); C2-second control (0.9% NaCl 1 mL/kg, i.p., 28 days); DM-diabetes mellitus (streptozotocin 100 mg/kg in 0.9% NaCl, i.p., 1 day); P-pyridoxine (7 mg/kg, i.p., 28 days); and DM + P-diabetes mellitus and pyridoxine (streptozotocin 100 mg/kg, i.p., 1 day and pyridoxine 7 mg/kg, i.p., 28 days). Pyridoxine treatment reduced CAT and MDH activity in diabetic rats. In diabetic rats, the administration of pyridoxine increased LDH1 and decreased LDH4 isoform activities, as well as decreased peroxisomal MDH and increased mitochondrial MDH activities. Our findings highlight the positive effects of pyridoxine administration on the complex interplay between oxidative stress, antioxidant enzymes, and metabolic changes in diabetic cardiomyopathy.
RESUMO
Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF-/- C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF-/-; MIF-/-+Bet; TAA group, which received TAA; TAA+Bet; MIF-/-+TAA; and MIF-/-+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-ß1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-ß1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice without MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-ß1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver.
RESUMO
The aim of this study was to investigate the effects of aerobic treadmill training regimen of four weeks duration on oxidative stress parameters, metabolic enzymes, and histomorphometric changes in the colon of hyperhomocysteinemic rats. Male Wistar albino rats were divided into four groups (n = 10, per group): C, 0.9% NaCl 0.2 mL/day subcutaneous injection (s.c.) 2x/day; H, homocysteine 0.45 µmol/g b.w./day s.c. 2x/day; CPA, saline (0.9% NaCl 0.2 mL/day s.c. 2x/day) and an aerobic treadmill training program; and HPA, homocysteine (0.45 µmol/g b.w./day s.c. 2x/day) and an aerobic treadmill training program. The HPA group had an increased level of malondialdehyde (5.568 ± 0.872 µmol/mg protein, p = 0.0128 vs. CPA (3.080 ± 0.887 µmol/mg protein)), catalase activity (3.195 ± 0.533 U/mg protein, p < 0.0001 vs. C (1.467 ± 0.501 U/mg protein), p = 0.0012 vs. H (1.955 ± 0.293 U/mg protein), and p = 0.0003 vs. CPA (1.789 ± 0.256 U/mg protein)), and total superoxide dismutase activity (9.857 ± 1.566 U/mg protein, p < 0.0001 vs. C (6.738 ± 0.339 U/mg protein), p < 0.0001 vs. H (6.015 ± 0.424 U/mg protein), and p < 0.0001 vs. CPA (5.172 ± 0.284 U/mg protein)) were detected in the rat colon. In the HPA group, higher activities of lactate dehydrogenase (2.675 ± 1.364 mU/mg protein) were detected in comparison to the CPA group (1.198 ± 0.217 mU/mg protein, p = 0.0234) and higher activities of malate dehydrogenase (9.962 (5.752-10.220) mU/mg protein) were detected in comparison to the CPA group (4.727 (4.562-5.299) mU/mg protein, p = 0.0385). Subchronic treadmill training in the rats with hyperhomocysteinemia triggers the colon tissue antioxidant response (by increasing the activities of superoxide dismutase and catalase) and elicits an increase in metabolic enzyme activities (lactate dehydrogenase and malate dehydrogenase). This study offers a comprehensive assessment of the effects of aerobic exercise on colonic tissues in a rat model of hyperhomocysteinemia, evaluating a range of biological indicators including antioxidant enzyme activity, metabolic enzyme activity, and morphometric parameters, which suggested that exercise may confer protective effects at both the physiological and morphological levels.
Assuntos
Antioxidantes , Hiper-Homocisteinemia , Ratos , Masculino , Animais , Catalase/metabolismo , Antioxidantes/farmacologia , Ratos Wistar , Malato Desidrogenase/metabolismo , Hiper-Homocisteinemia/induzido quimicamente , Hiper-Homocisteinemia/metabolismo , Solução Salina , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Homocisteína/metabolismo , Colo/metabolismoRESUMO
Osteoarthritis represents a leading cause of disability with limited treatment options. Furthermore, it is frequently accompanied by cardiovascular and cognitive disorders, which can be exacerbated by osteoarthritis or drugs used for its treatment. Here, we examined the behavioral and cardiac effects of the novel antidepressant vortioxetine in an osteoarthritis model, and compared them to duloxetine (an established osteoarthritis treatment). Osteoarthritis was induced in male and female rats with an intraarticular sodium-monoiodoacetate injection. Antidepressants were orally administered for 28 days following induction. During this period the acetone, burrowing and novel-object-recognition tests (NORT) were used to assess the effects of antidepressants on pain hypersensitivity (cold allodynia), animal well-being and cognitive performance, respectively. Following behavioral experiments, heart muscles were collected for assessment of redox status/histology. Antidepressant treatment dose-dependently reduced cold allodynia in rats with osteoarthritis. Duloxetine (but not vortioxetine) depressed burrowing behavior in osteoarthritic rats in a dose-related manner. Osteoarthritis induction reduced cognitive performance in NORT, which was dose-dependently alleviated by vortioxetine (duloxetine improved performance only in female rats). Furthermore, duloxetine (but not vortioxetine) increased oxidative stress parameters in the heart muscles of female (but not male) rats and induced histological changes in cardiomyocytes indicative of oxidative damage. Vortioxetine displayed comparable efficacy to duloxetine in reducing pain hypersensitivity. Furthermore, vortioxetine (unlike duloxetine) dose-dependently improved cognitive performance and had no adverse effect on burrowing behavior (animal surrogate of well-being) and cardiac redox status/histology. Our results indicate that vortioxetine could be a potential osteoarthritis treatment (with better characteristics compared to duloxetine).
Assuntos
Hipersensibilidade , Osteoartrite , Feminino , Animais , Ratos , Cloridrato de Duloxetina/farmacologia , Cloridrato de Duloxetina/uso terapêutico , Vortioxetina , Hiperalgesia , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Miócitos Cardíacos , Osteoartrite/tratamento farmacológico , CogniçãoRESUMO
The aim of this study was to examine the effects of hyperhomocysteinemia and aerobic physical activity on changes of cardiovascular biomarkers in sera, oxidative stress in cardiac tissue, and histomorphometric parameters of heart and aorta in rats. Experiments were conducted on male Wistar albino rats organized into four groups (n = 10, per group): C (control group): 0.9% NaCl 0.2 mL/day; H (homocysteine group): homocysteine 0.45 µmol/g b.w./day; CPA (control + physical activity group): 0.9% NaCl 0.2 mL/day and a program of physical activity on a treadmill; and HPA (homocysteine + physical activity group) homocysteine 0.45 µmol/g b.w./day and a program of physical activity on a treadmill. Substances were applied subcutaneously twice a day. Lipid peroxidation and relative activity of Mn-superoxide dismutase isoform were significantly higher in active hyperhomocysteinemic rats in comparison to sedentary animals. Atherosclerotic plaques were detected in aorta samples of active hyperhomocysteinemic rats and also, they had increased left ventricle wall and interventricular septum, and transverse diameter of cardiomyocytes compared to sedentary groups. Aerobic physical activity in the condition of hyperhomocysteinemia can lead to increased oxidative stress in cardiac tissue and changes in histomorphometric parameters of the heart and aorta, as well increased lipid parameters and cardiac damage biomarkers in sera of rats.
Assuntos
Hiper-Homocisteinemia , Animais , Ratos , Masculino , Solução Salina/farmacologia , Ratos Wistar , Estresse Oxidativo , Aorta/metabolismo , Exercício Físico , Biomarcadores/metabolismo , Homocisteína/farmacologiaRESUMO
Chronic stress has been implicated in the development and progression of heart disease. In the past decade, a link between chronic stress and cardiac fibrosis has been described. Here, we focused on investigating the effects of one of the key molecular effectors of the stress response-adrenocorticotropic hormone (ACTH) on cardiac histopathology. More importantly, as the literature data support interplay between magnesium (Mg) and the hypothalamo-pituitary-adrenal (HPA) stress system, we explored potential cardioprotective effects of Mg supplementation in a rat model of ACTH-induced cardiac remodeling. Protracted ACTH exposure in rats resulted in a prominent increase in proliferation of fibroblasts and excessive collagen deposition in the heart, accompanied by enhanced proliferation of cardiomyocytes and vascular endothelial cells. Our results show, for the first time, that administration of Mg in rats was effective in ameliorating the development of ACTH-evoked cardiac fibrosis, while facilitating cardiomyocyte proliferation. Furthermore, we propose that Mg supplementation attenuates ACTH-induced HPA axis hyperactivity, as one of the underlying plausible mechanisms, which may contribute to its cardioprotective effects.
Assuntos
Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Hormônio Adrenocorticotrópico , Animais , Proliferação de Células , Corticosterona , Células Endoteliais/metabolismo , Fibrose , Sistema Hipotálamo-Hipofisário/metabolismo , Magnésio , Miócitos Cardíacos/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , RatosRESUMO
BACKGROUND: During the last decades, the abuse of anabolic androgenic steroids (AASs) has become popular among professional and recreational athletes. The abuse of AASs leads to decreased levels of sex hormones, but the available literature a gives very small pool of data regarding the effects of swimming alone or combined with AASs on testicle tissue. The aim of this study was to investigate the effects of four-week administration of nandrolone decanoate and swimming training alone or in combination on morphometric parameters, androgen receptor (AR) and redox state in testicle tissue. The study included Wistar albino male rats, 10 weeks old, classified into 4 groups: control (T-N-), nandrolone (T-N+), swimming training (T+N-) and swimming training with nandrolone (T+N+). The rats from nandrolone (N+) groups received nandrolone decanoate 20 mg/kg b.w.once per week. The rats from training (T+) groups, swam 1 h/day 5 days/week. The isolated testicles were measured, left testicles were routinely processed for histological analysis, while right testicles were homogenized and prepared for the analysis of the following oxidative stress biomarkers: index of lipid peroxidation (TBARS), nitrites, catalase, superoxide dismutase (SOD), and reduced glutathione (GSH). RESULTS: Diameter, as well as cross-section area of seminiferous tubules were decreased by 10 % and 21 % (respectively) in the T-N+ group and by 15% and 41 % (respectively) in the T+N+ group compared to control. Interstitium of the testicles was decreased in all experimental groups. Reduction of immunoreactivity of AR in T-N+ group was 22 %, in T+N+ group was 9 % compared to control. TBARS levels were increased in T+N- and T+N+ groups. Nitrites were decreased in T+N+ group. Catalase activity was increased in all experimental groups. Swimming alone or combined with nandrolone decreased the level of GSH compared to control. SOD activity was decreased in T-N+ and T+N+ groups compared to control. CONCLUSIONS: Nandrolone alone or combined with swimming decreased morphometric parameters and amount of AR in testicle tissue. Changes in the redox state indicate reproductive dysfunction.
RéSUMé: CONTEXTE: Au cours des dernières décennies, l'abus de stéroïdes androgéniques anabolisants (SAA) est devenu populaire parmi les athlètes professionnels et récréatifs. L'abus des SAA conduit à une diminution des niveaux d'hormones sexuelles, mais la littérature sur les effets de la natation seule ou combinée avec des SAA sur les tissus testiculaires est encore très limité. Le but de cette étude était d'étudier les effets de l'administration de quatre semaines de décanoate de nandrolone et de l'entraînement à la natation seuls ou en combinaison sur les paramètres morphométriques, le récepteur aux androgènes (RA) et l'état redox dans le tissu testiculaire. L'étude a inclus des rats mâles Wistar albinos, âgés de 10 semaines, classés en 4 groupes: contrôle (T-N-), nandrolone (T-N+), entraînement à la natation (T+N-) et entraînement à la natation avec nandrolone (T+N+). Les rats des groupes nandrolone (N+) ont reçu du décanoate de nandrolone 20 mg/kg p.c. une fois par semaine. Les rats des groupes entraînement (T+) nageaient 1 h/jour 5 jours/semaine. Les testicules isolés ont été mesurés, les testicules gauches ont été systématiquement traités pour l'analyse histologique tandis que les testicules droits ont été homogénéisés et préparés pour l'analyse des biomarqueurs de stress oxydatif suivants: indice de peroxydation lipidique (TBARS), nitrites, catalase, superoxyde dismutase (SOD) et glutathion réduit (GSH). RéSULTATS: Le diamètre, ainsi que la section transversale des tubules séminifères ont été réduits de 10 % et 21 % (respectivement) dans le groupe T-N+ et de 15 % et 41 % (respectivement) dans le groupe T+N+ par rapport au groupe témoin. L'interstitium des testicules était diminué dans tous les groupes expérimentaux. La réduction de l'immunoréactivité de RA dans le groupe T-N+ était de 22 %, dans le groupe T+N+ était de 9 % par rapport au groupe témoin. Les niveaux de TBARS ont augmenté dans les groupes T+N- et T+N+. Les nitrites ont diminué dans le groupe T+N+. L'activité de la catalase a été augmentée dans tous les groupes expérimentaux. La natation seule ou combinée à la nandrolone a réduit le niveau de GSH par rapport au contrôle. L'activité de la SOD était diminuée dans les groupes T-N+ et T+N+ par rapport au contrôle. CONCLUSIONS: La nandrolone seule ou combinée à la natation a diminué les paramètres morphométriques et la quantité de RA dans le tissu testiculaire. Les changements de l'état redox indiquent un dysfonctionnement de la reproduction.
RESUMO
Nonalcoholic fatty liver disease (NAFLD) represents a hepatic manifestation of metabolic syndrome. The aim of this study was to examine the effect of betaine on ultrastructural changes in the mouse liver with methionine- and choline-deficient (MCD) diet-induced NAFLD. Male C57BL/6 mice were divided into groups: Control-fed with standard chow, BET-standard chow supplemented with betaine (1.5% w/v drinking water), MCD-fed with MCD diet, and MCD + BET-MCD diet with betaine supplementation for 6 weeks. Liver samples were taken for pathohistology and transmission electron microscopy. The MCD diet-induced steatosis, inflammation, and balloon-altered hepatocytes were alleviated by betaine. MCD diet induced an increase in mitochondrial size versus the control group (p < 0.01), which was decreased in the betaine-treated group. In the MCD diet-fed group, the total mitochondrial count decreased versus the control group (p < 0.01), while it increased in the MCD + BET group versus MCD (p < 0.01). Electron microscopy showed an increase in the number of autophagosomes in the MCD and MCD + BET group versus control, and a significant difference in autophagosomes number was detected in the MCD + BET group by comparison with the MCD diet-treated group (p < 0.05). Betaine decreases the number of enlarged mitochondria, alleviates steatosis, and increases the number of autophagosomes in the liver of mice with NAFLD.
Assuntos
Betaína/farmacologia , Colina/metabolismo , Dieta , Suplementos Nutricionais , Fígado/efeitos dos fármacos , Fígado/ultraestrutura , Metionina/deficiência , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Colágeno , Modelos Animais de Doenças , Hepatócitos/efeitos dos fármacos , Hepatócitos/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Voltage-gated potassium (Kv) channels are the largest superfamily of potassium (K) channels. A variety of Kv channels are expressed in the vascular smooth muscle cells (SMC). Studies have shown that gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) cause various changes in the human umbilical vein (HUV). Recently, we have shown that 4-AP, a nonspecific Kv1-4 channel inhibitor, significantly decreases vasorelaxation induced by K channel opener pinacidil in vascular SMCs of the HUVs from normal pregnancies, but not in GDM and PIH. The goal of this study was to provide more detailed insight in the Kv channel subtypes involved in pinacidil-induced vasodilation of HUVs, as well as to investigate potential alterations of their function and expression during GDM and PIH. Margatoxin, a specific blocker of Kv1.2 and Kv1.3 channels, significantly antagonized pinacidil-induced vasorelaxation in normal pregnancy, while in HUVs from GDM and PIH that was not the case, indicating damage of Kv1.2 and Kv1.3 channel function. Immunohistochemistry and Western blot revealed similar expression of Kv1.2 channels in all groups. The expression of Kv1.3 subunit was significantly decreased in PIH, while it remained unchanged in GDM compared to normal pregnancy. Phrixotoxin, specific blocker of Kv4.2 and Kv4.3 channels, did not antagonize response to pinacidil in any of the groups. The major novel findings show that margatoxin antagonized pinacidil-induced relaxation in normal pregnancy, but not in GDM and PIH. Decreased expression of Kv1.3 channels in HUV during PIH may be important pathophysiological mechanism contributing to an increased risk of adverse pregnancy outcomes.
Assuntos
Hipertensão Induzida pela Gravidez/metabolismo , Canal de Potássio Kv1.3/metabolismo , Músculo Liso Vascular/metabolismo , Veias Umbilicais/metabolismo , Adulto , Anti-Hipertensivos/farmacologia , Diabetes Gestacional/metabolismo , Feminino , Humanos , Canal de Potássio Kv1.2/metabolismo , Pinacidil/farmacologia , Gravidez , Adulto JovemRESUMO
Heart failure (HF) is one of the major cardiovascular causes of death worldwide. In this study, we explored the effects of folic acid (FA) on cardiometabolic, oxidative stress biomarker changes, and the activity of proliferation marker Ki67 in monocrotaline-induced HF. The research was conducted during a 4 week period using five experimental groups (eight animals per group): blank solution exposed controls (C1: 1 mL/kg physiological saline, 1 day; C2: 1 mL/kg physiological saline, 28 days), monocrotaline (MCT) induced HF (50 mg/kg MCT), FA (5 mg·kg-1·day-1 FA), and MCT+FA (50 mg/kg MCT, 5 mg·kg-1·day-1 FA). Superoxide dismutase and glutathione peroxidase activities together with total glutathione and parameters of oxidative damage of proteins were determined in cardiac tissue as well as cardiometabolic parameters in plasma or serum. The total glutathionylation was determined by Western blot and proliferation marker Ki67 was assessed by immunohistochemistry. The right ventricular (RV) wall hypertrophy and Ki67 positivity, accompanied by a significant increase of troponin T, has been shown in MCT-induced HF. The antioxidant effect of FA was reflected through superoxide dismutase activity, reduced Ki67 positivity in the RV wall, and a slightly decreased total glutathionylation level.
Assuntos
Antioxidantes/farmacologia , Metabolismo Energético/efeitos dos fármacos , Ácido Fólico/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Glutationa/metabolismo , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Masculino , Monocrotalina , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos Wistar , Remodelação Ventricular/efeitos dos fármacosRESUMO
Metallophilic macrophages (MMs) are a distinct cell type of the rodent thymus. Our previous research has focused on the morphological characteristics of MMs, as well as on the molecular mechanisms involved in the development and tissue positioning of these cells. However, the postnatal development of MMs has not been sufficiently studied. In the present study, we investigated the positioning of MMs in the rat thymus between postnatal day 0 (P0) and P30. On P0, MMs were evenly distributed all over the thymic tissue-that is, the cortex, cortico-medullary zone and medulla. From P0 to P15, the number of MMs in the thymic cortex significantly decreased, and after P15, this number did not change. Thus, the present study shows that on P15, MMs almost completely disappear from the thymic cortex and show their adult position in the cortico-medullary zone and in the medulla.
Assuntos
Macrófagos/citologia , Prata/metabolismo , Timo/citologia , Análise de Variância , Animais , Intervalos de Confiança , Feminino , Imuno-Histoquímica , Macrófagos/metabolismo , Masculino , Método de Monte Carlo , Ratos , Ratos Wistar , Análise de Regressão , Coloração pela Prata , Timo/crescimento & desenvolvimentoRESUMO
The aim of this study was to test the hypothesis that subchronic co-application of vitamins B6 and folic acid (FA) could affect heart failure (HF) induced by monocrotaline (MCT), with the modulation of oxidative stress parameters and cardiometabolic biomarkers. Biochemical and histomorphometric analyses were assessed in blank solution-exposed controls (C1 physiological saline 1 mL/kg, 1 day, n = 8; C2 physiological saline 1 mL/kg, 28 days, n = 8), MCT-induced HF (MCT 50 mg/kg, n = 8), B6+FA (vitamin B6 7 mg·kg-1·day-1, FA 5 mg·kg-1·day-1; n = 8), and MCT+B6+FA (MCT 50 mg/kg, vitamin B6 7 mg·kg-1·day-1, FA 5 mg·kg-1·day-1; n = 8) in male Wistar albino rats (body mass 160 g at the start). Superoxide dismutase and glutathione peroxidase activities, thiol-, carbonyl groups, and nitrotyrosine were determined in cardiac tissue. Echocardiography was performed to confirm MCT-induced HF. The right ventricular wall hypertrophy, accompanied with significant increase of troponin T and preserved renal and liver function, has been shown in MCT-induced HF. However, these effects were not related to antioxidant effects of vitamin B6 and FA, since several parameters of oxidative stress were more pronounced after treatment. In this study, co-application of vitamins B6 and FA did not attenuate hypertrophy of the right ventricle wall but aggravated oxidative stress, which is involved in HF pathogenesis.
Assuntos
Ácido Fólico/administração & dosagem , Ácido Fólico/farmacologia , Insuficiência Cardíaca/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Vitamina B 6/administração & dosagem , Vitamina B 6/farmacologia , Animais , Biomarcadores/metabolismo , Eletrocardiografia/efeitos dos fármacos , Coração/efeitos dos fármacos , Coração/fisiopatologia , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/fisiopatologia , Masculino , Monocrotalina/efeitos adversos , Ratos , Ratos Wistar , Fatores de TempoRESUMO
This study was conducted to explore the effects of sulfur containing amino acids on redox status and morphological parameters in the rat ileum tissue. Male Wistar albino rats were randomly divided into the following groups: Group K (saline (1 ml/day, i.p.)), Group M (methionine (0.8 mmol/kg/day, i.p.)), Group C (methionine (0.8 mmol/kg/day) + L-cysteine (7 mg/kg/day), i.p.) and Group N (methionine (0.8 mmol/kg/day) + N-acetyl-L-cysteine (50 mg/kg/day), i.p.). Activities of antioxidant enzymes in the ileum were analyzed to profile oxidative status. Morphometric analysis included measurement of villus height (µm), tunica mucosa thickness (µm), tunica muscularis thickness (µm), the total thickness of the ileal wall (µm) and the number of cells in the lamina propria (per 0.1 mm2 of tissue). Results showed that methionine treatment reduced the activity of antioxidant enzymes (SOD, GPx, CAT) and the GSH content compared to the control group (p > 0.05). The application of methionine reduced the following parameters statistically significant compared to the control group: length of the ileal villi (p < 0.01), tunica mucosa thickness (p < 0.01), and ileal wall thickness (p < 0.01). We concluded that methionine induced the changes in the gut redox status, which implied oxidative stress occurrence. L-cysteine and N-acetyl-L-cysteine both exhibited antioxidant properties.
Assuntos
Estresse Oxidativo , Animais , Íleo , Masculino , Metionina , Oxirredução , Ratos , Ratos WistarRESUMO
Gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) can jeopardize mother and/or fetus. Vascular ATP-sensitive potassium (KATP) channels most likely participate in the processes of diabetes and hypertension. The aim of this research was to examine whether GDM and PIH cause changes in the expression and function of KATP channels in vascular smooth muscle of human umbilical vein (HUV). Western blot and immunohistochemistry detected significantly decreased expression of Kir6.1 subunit of KATP channels in GDM and PIH, while the expression of SUR2B was unchanged. In GDM, a K+ channel opener, pinacidil caused reduced relaxation of the endothelium-denuded HUVs compared to normal pregnancy. However, its effects in HUVs from PIH subjects were similar to normal pregnancy. In all groups KATP channel blocker glibenclamide antagonized the relaxation of HUV induced by pinacidil without change in the maximal relaxations indicating additional KATP channel-independent mechanisms of pinacidil action. Iberiotoxin, a selective antagonist of large-conductance calcium-activated potassium channels, inhibited the relaxant effect of pinacidil in PIH, but not in normal pregnancy and GDM. Experiments performed in K+-rich solution confirmed the existence of K+-independent effects of pinacidil, which also appear to be impaired in GDM and PIH. Thus, the expression of KATP channels is decreased in GDM and PIH. In GDM, vasorelaxant response of HUV to pinacidil is reduced, while in PIH it remains unchanged. It is very likely that KATP channels modulation and more detailed insight in KATP channel-independent actions of pinacidil may be precious in the therapy of pathological pregnancies.
Assuntos
Trifosfato de Adenosina/metabolismo , Diabetes Gestacional/fisiopatologia , Hipertensão Induzida pela Gravidez/fisiopatologia , Canais KATP/metabolismo , Músculo Liso Vascular/metabolismo , Veias Umbilicais/metabolismo , Adulto , Feminino , Humanos , Músculo Liso Vascular/patologia , Gravidez , Veias Umbilicais/patologiaRESUMO
This study investigated different dietary strategies, high-fat (HFd), or standard diet (Sd) alone or in combination with standardized Aronia melanocarpa extract (SAE), as a polyphenol-rich diet, and their effects on lipids and fatty acids (FA) in rats with metabolic syndrome (MetS). Wistar albino rats were randomly divided into two groups: healthy and rats with MetS, and then depending on dietary patterns on six groups: healthy rats fed with Sd, healthy rats fed with Sd and SAE, rats with MetS fed with HFd, rats with MetS fed with HFd and SAE, rats with MetS fed with Sd, and rats with MetS fed with Sd and SAE. 4 weeks later, after an overnight fast (12-14 h), blood for determination of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), index of lipid peroxidation (measured as TBARS), and FA was collected. Increased FA and lipid concentration found in MetS rats were reduced when changing dietary habits from HFd to Sd with or without SAE consumption. Consumption of SAE slightly affects the FA profiles, mostly palmitoleic acid in healthy rats and PUFA in MetS + HFd rats. Nevertheless, in a high-fat diet, SAE supplementation significantly decreases n-6/n-3 ratio, thereby decreasing systemic inflammation. Further researches are warranted to confirm these effects in humans.
Assuntos
Dieta , Suplementos Nutricionais , Ácidos Graxos/sangue , Photinia/química , Extratos Vegetais/farmacologia , Animais , Ácidos Graxos Dessaturases/sangue , Elongases de Ácidos Graxos/sangue , Masculino , Ratos WistarRESUMO
The aim of this study was to examine the effects of folic acid administration on the antioxidant enzyme (superoxide dismutase (SOD) and catalase (CAT)) activities, lactate and malate dehydrogenase (LDH and MDH) activities, and certain LDH and MDH isoform distribution in the cardiac tissue of diabetic Wistar male rats. Diabetes mellitus (DM) was induced by streptozotocin (STZ). There were five groups: C1-control (physiological saline 1 ml/kg, i.p. one day), C2-control with daily physiological saline treatment (1 ml/kg, i.p. 28 days), DM-diabetes mellitus (STZ 100 mg/kg in physiological saline, i.p. one day), FA-folic acid (5 mg/kg in physiological saline, i.p. 28 days), and DM+FA-diabetes mellitus and folic acid group (STZ 100 mg/kg in physiological saline, i.p. one day, and folic acid 5 mg/kg in physiological saline, i.p. 28 days). After four weeks, animal hearts were isolated for measurement of enzyme activities, as well as for histomorphometry analyses. An elevated glucose level and a decreased insulin level were obtained in the DM group. SOD, CAT, and MDH activities were elevated in the DM group, while there was no difference in LDH activity among the groups. In all tested groups, four LDH and three MDH isoforms were detected in the heart tissue, but with differences in their relative activities among the groups. Left ventricular cardiomyocyte transversal diameters were significantly smaller in both diabetic groups. Folic acid treatment of diabetic rats induced a reduced glucose level and reduced CAT, SOD, and MDH activities and alleviated the decrease in cardiomyocyte diameters. In conclusion, increased activities of antioxidant enzymes and MDH may be the consequence of oxidative stress caused by DM. Administration of the folic acid has a protective effect since it leads to reduction in glycemia and activities of the certain examined enzymes in the rats with experimentally induced DM.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Ácido Fólico/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Glicemia/efeitos dos fármacos , Catalase/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Oxirredução/efeitos dos fármacos , Ratos , Ratos Wistar , Estreptozocina/toxicidade , Superóxido Dismutase/metabolismoRESUMO
Diabetes mellitus (DM) is a metabolic disorder that causes severe complications. Thus, the aims of this study were to investigate the influence of DM and folic acid treatment on liver and renal biomarkers, and heart remodeling through evaluation of cardiac matrix metalloproteinase (MMP) activity. There were 4 groups: control (physiological saline 1 mL/kg, i.p., 28 days), DM (streptozotocin [STZ] 100 mg/kg in physiological saline, i.p., 1 day), folic acid (FA; 5 mg/kg, i.p., 28 days), and DM+FA (STZ 100 mg/kg, i.p., 1 day and folic acid 5 mg/kg, i.p., 28 days). Our results demonstrated increased aminotransferase and alkaline phosphatase activity, urea and creatinine concentration, and decreased albumin and fibrinogen concentration in the DM group. MMP-2 relative activity was elevated in the DM and FA groups; MMP-9 was decreased in the DM and increased in the FA group. The folic acid treatment of diabetic rats did not change aminotransferase activity; it alleviated the increase in alkaline phosphatase and the decrease in albumin and fibrinogen concentration, and reduced MMP-2 activity; however, it increased urea and creatinine concentration. In conclusion, folic acid treatment of diabetic rats has cardio- and hepato-protective effects. However, its dosing should be carefully considered because of possible renal damage.
Assuntos
Diabetes Mellitus Experimental/enzimologia , Ácido Fólico/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , Miocárdio/enzimologia , Miocárdio/patologia , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Ácido Fólico/administração & dosagem , Rim/metabolismo , Fígado/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
We examined the effects of betaine, an endogenous and dietary methyl donor essential for the methionine-homocysteine cycle, on oxidative stress, inflammation, apoptosis, and autophagy in methionine-choline deficient diet (MCD)-induced non-alcoholic fatty liver disease (NAFLD). Male C57BL/6 mice received standard chow (control), standard chow and betaine (1.5% w/v in drinking water), MCD, or MCD and betaine. After six weeks, serum and liver samples were collected for analysis. Betaine reduced MCD-induced increase in liver transaminases and inflammatory infiltration, as well as hepatosteatosis and serum levels of low-density lipoprotein, while it increased that of high-density lipoprotein. MCD-induced hepatic production of reactive oxygen and nitrogen species was significantly reduced by betaine, which also improved liver antioxidative defense by increasing glutathione content and superoxide-dismutase, catalase, glutathione peroxidase, and paraoxonase activity. Betaine reduced the liver expression of proinflammatory cytokines tumor necrosis factor and interleukin-6, as well as that of proapoptotic mediator Bax, while increasing the levels of anti-inflammatory cytokine interleukin-10 and antiapoptotic Bcl-2 in MCD-fed mice. In addition, betaine increased the expression of autophagy activators beclin 1, autophagy-related (Atg)4 and Atg5, as well as the presence of autophagic vesicles and degradation of autophagic target sequestosome 1/p62 in the liver of NAFLD mice. The observed effects of betaine coincided with the increase in the hepatic phosphorylation of mammalian target of rapamycin (mTOR) and its activator Akt. In conclusion, the beneficial effect of betaine in MCD-induced NAFLD is associated with the reduction of liver oxidative stress, inflammation, and apoptosis, and the increase in cytoprotective Akt/mTOR signaling and autophagy.
Assuntos
Betaína/uso terapêutico , Deficiência de Colina/metabolismo , Metionina/deficiência , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Betaína/farmacologia , Deficiência de Colina/complicações , Fármacos Gastrointestinais/farmacologia , Fármacos Gastrointestinais/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in the methylation and transsulfuration pathways; methionine-rich diets were used to induce hyperhomocysteinemia, and cardiovascular pathology was often observed. Other sulfur amino acids interfere with this metabolism, i.e., L-cysteine (Cys) and N-aceyl-L-cysteine (NAC), and probably also affect cardiovascular system. Their effects are controversial due to their ability to act both as anti- or pro-oxidant. Thus, this study aimed to elucidate their influence on levels of homocysteine, folate and vitamin B12, levels of different haemostatic parameters (fibrinogen, D-dimer, vWF Ag, vWF Ac) in rat serum or plasma as well as their effects on cardiac and aortic tissue histology in subchronically methionine-treated rats. Wistar albino rats were divided into 4 experimental groups: (a) control group (0.9% sodium chloride 0.1-0.2 mL/day) (n = 10) (K); (b) DL-methionine (0.8 mmol/kg/bw/day) (n = 10) (M); (c) DL-methionine (0.8 mmol/kg/bw/day) + L-cysteine (7 mg/kg/bw/day) (n = 8) (C); (d) DL-methionine (0.8 mmol/ kg/bw/day) + N-acetyl-L-cysteine (50 mg/kg/bw/day) (n = 8) (N). All substances were applied i.p., treatment duration 3 weeks. Lower levels of vitamin B12 in all the groups were found. Folate was reduced only in N group. Decreased fibrinogen was noted in C and N groups and increased D-dimer only in C. VWF activity was reduced in M and C groups. Deleterious effects in heart were observed, especially after Cys and NAC application. Aortic tissue remained unchanged. In conclusion, it could be said that sulfur amino acids have the significant impact on cardiovascular system in subchronically methionine-treated rats. This study points out the relevance of their complex interactions and deleterious effects mediated by either direct influence or procoagulant properties.