Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
1.
J Proteome Res ; 15(10): 3872-3882, 2016 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-27604906

RESUMO

To obtain more information into the molecular mechanisms underlying ovarian cancer (OC), we proposed a comparative proteomic analysis in animals receiving long-term melatonin as therapy or only vehicle using multidimensional protein identification combined with mass spectrometry. To induce tumor, a single dose of 100 µg 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 µL of sesame oil was injected under the left ovarian bursa of 20 Fischer 344 rats. The right ovaries were injected with sesame oil only. After tumors were developed, half of the animals received intraperitoneal administration of melatonin (200 µg/100g body weight/day) for 60 days. Melatonin therapy promoted down-regulation in numerous proteins involved in OC signaling pathways. The most significant portion of these proteins are involved in several metabolic processes, mainly those associated with mitochondrial systems, generation of metabolites and energy, hypoxia-inducible factor-1 signaling, antigen processing and presentation, endoplasmic reticulum stress-associated pathways, and cancer-related proteoglycans. A small number of proteins that were overexpressed by melatonin therapy included ATP synthase subunit ß, fatty acid-binding protein, and 10-kDa heat shock protein. Taken together, our findings suggest that melatonin therapy efficiently modulated important signaling pathways involved in OC, and these proteins might be further targets that should be explored in new therapeutic opportunities for OC.


Assuntos
Melatonina/farmacologia , Redes e Vias Metabólicas/efeitos dos fármacos , Neoplasias Ovarianas/metabolismo , Proteômica/métodos , 9,10-Dimetil-1,2-benzantraceno , Animais , Modelos Animais de Doenças , Feminino , Melatonina/uso terapêutico , Proteínas de Neoplasias/efeitos dos fármacos , Neoplasias Ovarianas/induzido quimicamente , Ratos Endogâmicos F344 , Transdução de Sinais/efeitos dos fármacos
2.
Indian J Biochem Biophys ; 51(3): 215-22, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25204084

RESUMO

Alcoholism and obesity are strongly associated with several disorders including heart and liver diseases. This study evaluated the effects of rutin treatment in serum, heart and liver tissues of rats subjected to a combination of hypercaloric diet (HD) and chronic ethanol consumption. Rats were divided into three groups: Control: rats fed a standard diet and drinking water ad libitum; G1: rats fed the HD and receiving a solution of 10% (v/v) ethanol; and G2: rats fed the HD and ethanol solution, followed by injections of 50 mg/kg(-1) rutin as treatment. After 53 days of HD and ethanol exposure, the rutin was administered every three days for nine days. At the end of the experimental period (95 days), biochemical analyses were carried out on sera, cardiac and hepatic tissues. Body weight gain and food consumption were reduced in both the G1 and G2 groups compared to control animals. Rutin effectively reduced the total lipids (TL), triglycerides (TG), total cholesterol (TC), VLDL, LDL-cholesterol and glucose levels, while it increased the HDL-cholesterol in the serum of G2 rats, compared to G1. Although rutin had no effect on total protein, albumin, uric acid and cretinine levels, it was able to restore serum activities of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) in animals fed HD and receiving ethanol. Glycogen stores were replenished in both hepatic and cardiac tissues after rutin treatment. Moreover, rutin consistently reduced hepatic levels of TG and TC and cardiac AST, ALT and CK activities. Thus, rutin treatment was effective in reducing the risk factors for cardiac and hepatic disease caused by both HD and chronic ethanol consumption.


Assuntos
Biomarcadores/metabolismo , Dieta Hiperlipídica/efeitos adversos , Etanol/toxicidade , Índice Glicêmico/efeitos dos fármacos , Coração/efeitos dos fármacos , Lipídeos/análise , Fígado/efeitos dos fármacos , Rutina/farmacologia , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Depressores do Sistema Nervoso Central/toxicidade , Creatina Quinase/metabolismo , Coração/fisiologia , L-Lactato Desidrogenase/metabolismo , Fígado/citologia , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar
3.
Pathol Res Pract ; 253: 155056, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38183817

RESUMO

In addition to its highly aggressive nature and late diagnosis, hepatocellular carcinoma (HCC) does not respond effectively to available chemotherapeutic agents. The search is on for an ideal and effective compound with low cost and minimal side effects that can be used as an adjunct to chemotherapeutic regimens. One of the mechanisms involved in the pathology of HCC is the oxidative stress, which plays a critical role in tumor survival and dissemination. Our group has already demonstrated the antitumor potential of melatonin against HuH 7.5 cells. In the present study, we focused on the effects of melatonin on oxidative stress parameters and their consequences on cell metabolism. HuH 7.5 cells were treated with 2 and 4 mM of melatonin for 24 and 48 h. Oxidative stress biomarkers, antioxidant enzyme, mitochondrial membrane potential, formation of lipid bodies and autophagic vacuoles, cell cycle progression, cell death rate and ultrastructural cell alterations were evaluated. The treatment with melatonin increased oxidative stress biomarkers and reduced antioxidant enzyme activities of HuH 7.5 cells. Additionally, melatonin treatment damaged the mitochondrial membrane and increased lipid bodies and autophagic vacuole formation. Melatonin triggered cell cycle arrest and induced cell death by apoptosis. Our results indicate that the treatment of HuH 7.5 cells with melatonin impaired antioxidant defense systems, inhibited cell cycle progression, and caused metabolic stress, culminating in tumor cell death.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Melatonina , Humanos , Carcinoma Hepatocelular/patologia , Melatonina/farmacologia , Melatonina/uso terapêutico , Antioxidantes/uso terapêutico , Neoplasias Hepáticas/patologia , Estresse Oxidativo , Biomarcadores/metabolismo , Apoptose
4.
Reprod Biol Endocrinol ; 9: 108, 2011 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-21810236

RESUMO

BACKGROUND: Melatonin is associated with direct or indirect actions upon female reproductive function. However, its effects on sex hormones and steroid receptors during ovulation are not clearly defined. This study aimed to verify whether exposure to long-term melatonin is able to cause reproductive hormonal disturbances as well as their role on sex steroid receptors in the rat ovary, oviduct and uterus during ovulation. METHODS: Twenty-four adult Wistar rats, 60 days old (+/-250 g) were randomly divided into two groups. Control group (Co): received 0.9% NaCl 0.3 mL+95% ethanol 0.04 mL as vehicle; Melatonin-treated group (MEL): received vehicle+melatonin [100 µg/100 g BW/day] both intraperitoneally during 60 days. All animals were euthanized by decapitation during the morning estrus at 4 a.m. RESULTS: Melatonin significantly reduced the plasma levels of LH and 17 beta-estradiol, while urinary 6-sulfatoximelatonin (STM) was increased at the morning estrus. In addition, melatonin promoted differential regulation of the estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and melatonin receptor (MTR) along the reproductive tissues. In ovary, melatonin induced a down-regulation of ER-alpha and PRB levels. Conversely, it was observed that PRA and MT1R were up-regulated. In oviduct, AR and ER-alpha levels were down-regulated, in contrast to high expression of both PRA and PRB. Finally, the ER-beta and PRB levels were down-regulated in uterus tissue and only MT1R was up-regulated. CONCLUSIONS: We suggest that melatonin partially suppress the hypothalamus-pituitary-ovarian axis, in addition, it induces differential regulation of sex steroid receptors in the ovary, oviduct and uterus during ovulation.


Assuntos
Estradiol/sangue , Tubas Uterinas/metabolismo , Hormônio Luteinizante/sangue , Melatonina/farmacologia , Ovário/metabolismo , Receptores de Esteroides/metabolismo , Útero/metabolismo , Animais , Tubas Uterinas/efeitos dos fármacos , Feminino , Ovário/efeitos dos fármacos , Ovulação , Ratos , Ratos Wistar , Receptor MT1 de Melatonina/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Útero/efeitos dos fármacos
5.
Alcohol Clin Exp Res ; 35(8): 1498-508, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21438888

RESUMO

BACKGROUND: Chronic ethanol intake leads to reproductive damage including reactive oxygen species formation, which accelerates the oxidative process. Melatonin is known to regulate the reproductive cycle, food/liquid intake, and it may also act as a potent antioxidant indoleamine. The aim of this study was to verify the effects of alcoholism and melatonin treatment on overall feed efficiency and to analyze its protective role against the oxidative stress in the ovarian tissue of UChB rats (submitted to 10% [v/v] voluntary ethanol consumption). METHODS: Forty adult female rats (n = 10/group) were finally selected for this study: UChB Co: drinking water only; and UChB EtOH: drinking ethanol at 2 to 6 ml/100 g/d + water, both receiving 0.9% NaCl + 95% ethanol 0.04 ml as vehicle. Concomitantly, UChB Co + M and UChB EtOH + M groups were infused with vehicle + melatonin (100 µg/100 g body weight/d) intraperitoneally over 60 days. All animals were euthanized by decapitation during the morning estrus (4 am). RESULTS: Body weight gain was reduced with ethanol plus melatonin after 40 days of treatment. In both melatonin-treated groups, it was observed a reduction in food-derived calories and liquid intake toward the end of treatment. The amount of consumed ethanol dropped during the treatment. Estrous cycle was longer in rats that received both ethanol and melatonin, with prolonged diestrus. Following to oxidative status, lipid hydroperoxide levels were higher in the ovaries of ethanol-preferring rats and decreased after melatonin treatment. Additionally, antioxidant activities of superoxide dismutase, glutathione peroxidase activity, and glutathione reductase activity were increased in melatonin-treated groups. CONCLUSIONS: We suggest that melatonin is able to affect feed efficiency and, conversely, it protects the ovaries against the oxidative stress arising from ethanol consumption.


Assuntos
Antioxidantes/farmacologia , Melatonina/farmacologia , Ovário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Consumo de Bebidas Alcoólicas/patologia , Animais , Antioxidantes/administração & dosagem , Peso Corporal/efeitos dos fármacos , Depressores do Sistema Nervoso Central/farmacologia , Depressores do Sistema Nervoso Central/toxicidade , Ciclo Estral/efeitos dos fármacos , Etanol/farmacologia , Etanol/toxicidade , Comportamento Alimentar/efeitos dos fármacos , Feminino , Índice Glicêmico/efeitos dos fármacos , Injeções Intraperitoneais , Melatonina/administração & dosagem , Ovário/lesões , Substâncias Protetoras/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Fatores de Tempo
6.
Artigo em Inglês | MEDLINE | ID: mdl-19001480

RESUMO

This study was designed to determine whether N-acetylcysteine (NAC, C(5)H(9)-NO(3)S), a compound from Allium species may be used as a complementary therapeutic agent, to inhibit high-sucrose induced-obesity and its effects on glucose tolerance, in vivo low-density lipoprotein (LDL)-oxidation and serum oxidative stress in rats. Initially, 24 male Wistar rats were divided into two groups: controls receiving standard chow (C, n = 6) and those receiving high-sucrose diet (HS, n = 18). After 22 days, (HS) group was divided into three groups (n = 6/group); (HS-HS) continued to eat high-sucrose diet and water; (HS-N) continued to eat high-sucrose diet and received 2 mg l(-1)-NAC in its drinking water; (HS-CN) changing high-sucrose to standard chow and receiving 2 mg l(-1)-NAC in its drinking water. After 22 days of the HS-group division (44 days of experimental period) body weight, body mass index and surface area were enhanced in HS-HS rats (P < .001). HS-HS rats had glucose intolerance, increased serum triacylglycerol (TG), very low-density lipoprotein (VLDL), oxidized-LDL (ox-LDL) and lipid-hydroperoxide (LH) than the others (P < .01). NAC in HS-N and HS-CN rats reduced the obesity markers, feed efficiency, LH and ox-LDL, as well normalized glucose response, TG and VLDL (P < .01) in these groups compared with HS-HS. Total antioxidant substances, GSH/GSSG ratio and glutathione-reductase, were higher in HS-N than in HS-HS (P < .01). In conclusion, NAC improved high-sucrose diet-induced obesity and its effects on glucose tolerance, lipid profile, in vivo LDL-oxidation and serum oxidative stress, enhancing antioxidant defences. The application of this agent may be feasible and beneficial for high-sucrose diet-induced obesity, which certainly would bring new insights on obesity-related adverse effects control.

7.
Nutr J ; 9: 46, 2010 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-20958965

RESUMO

BACKGROUND: Olive oil and its minor constituents have been recommended as important dietary therapeutic interventions in preventive medicine. However, a question remains to be addressed: what are the effects of olive oil and its phenolic compounds on obesity-induced cardiac metabolic changes? METHODS: Male Wistar rats were divided into two groups (n = 24/group): (C) receiving standard-chow; (Ob) receiving hypercaloric-chow. After 21 days C and Ob groups were divided into four subgroups (n = 6/group):(C) standard-chow and saline; (C-Olive)standard-chow and olive-oil (3.0 g/kg.day); (C-Oleuropein)standard-chow and oleuropein (0.023 mg/kg/day); (C-Cafeic) standard-chow and cafeic-acid (2.66 mg/kg/day); (Ob)receiving hypercaloric-chow and saline;(Ob-Olive) hypercaloric-chow and olive-oil;(Ob-Oleuropein) hypercaloric-chow and oleuropein;(Ob-Cafeic) hypercaloric-chow and cafeic-acid. Treatments were given twice a week during 21 days. RESULTS: After 42 days, obesity was evidenced in Ob rats from enhanced body-weight, surface-area, and body-mass-index. Energy-expenditure, oxygen consumption(VO2) and fat-oxidation were lower in Ob-group than in C. Despite no morphometric changes, Ob-Olive, Ob-Oleuropein and Ob-Cafeic groups had higher VO2, fat-oxidation, myocardial beta-hydroxyacyl coenzyme-A dehydrogenase and lower respiratory-quotient than Ob. Citrate-synthase was highest in Ob-Olive group. Myocardial lipid-hydroperoxide(LH) and antioxidant enzymes were unaffected by olive-oil and its compounds in obesity condition, whereas LH was lower and total-antioxidant-substances were higher in C-Olive and C-Oleuropein than in C. CONCLUSIONS: The present study demonstrated for the first time that olive-oil, oleuropein and cafeic-acid enhanced fat-oxidation and optimized cardiac energy metabolism in obesity conditions. Olive oil and its phenolic compounds improved myocardial oxidative stress in standard-fed conditions.


Assuntos
Ácidos Cafeicos/farmacologia , Miocárdio/metabolismo , Obesidade/metabolismo , Óleos de Plantas/farmacologia , Piranos/farmacologia , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Animais , Calorimetria , Citrato (si)-Sintase/metabolismo , Glucosídeos Iridoides , Iridoides , Masculino , Obesidade/fisiopatologia , Azeite de Oliva , Fenóis/farmacologia , Ratos , Ratos Wistar
8.
Toxicol Rep ; 6: 244-252, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30911467

RESUMO

Bisphenol A (BPA) is an abundant raw material applied in the production of daily necessities, such as food cans, baby bottles, electronic and medical equipment. Phytotherapeutic use of plant preparations has long been known for multiple target medicinal uses. The species Bauhinia forficata is widely used as hypoglycemic, anti-inflammatory, antioxidant, diuretic and hypocholesterolemic agent. The aim of this study was to verify the effects of B. forficata extract in association with BPA exposure on serological parameters, hepatic antioxidant status and glycogen store capacity in Wistar rats. B. forficata was able to reduce BPA-induced glucose levels; it also prevented the early glucose elevation in control and BPA-exposed animals after the glucose provocative test. This effect was related to the hepatic glycogen content; while BPA reduced the hepatic glycogen deposits B. forficata treatment contributed to minimize it. BPA and B. forficata singly caused elevation in triacylglycerol and VLDL levels and reduction in cholesterol and LDL concentrations. BPA increased hepatic malondialdehyde levels and reduced catalase activity, thus inducing liver oxidative stress. Conversely, B. forficata treatment reduced malondialdehyde concentration without interfering with catalase activity; this antioxidant capacity is attributed to the flavonoids content (e.g., kaempferol and myricetin). Based on these results, we demonstrated that B. forficata commercial extract has hypoglycemic and antioxidant properties capable of minimizing the effects of BPA. However, it should be considered that the consumption of herbal commercial extract must be judicious to avoid deleterious health effects.

9.
Eur J Pharmacol ; 579(1-3): 318-25, 2008 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-18054909

RESUMO

Studies on conjugated linoleic acid ingestion and its effect on cardiac tissue are necessary for the safe utilization of this compound as supplement for weight loss. Male Wistar 24-rats were divided into four groups (n=6):(C)given standard chow, water and 0.5 ml saline, twice a week by gavage; (C-CLA)receiving standard chow, water and 0.5 ml of conjugated linoleic acid, twice a week, by gavage; (S)given standard chow, saline by gavage, and 30% sucrose in its drinking water; (S-CLA)receiving standard chow, 30% sucrose in its drinking water and conjugated linoleic acid. After 42 days of treatment S rats had obesity with increased abdominal-circumference, dyslipidemia, oxidative stress and myocardial lower citrate synthase(CS) and higher lactate dehydrogenase(LDH) activities than C. Conjugated linoleic acid had no effects on morphometric parameters in C-CLA, as compared to C, but normalized morphometric parameters comparing S-CLA with S. There was a negative correlation between abdominal adiposity and resting metabolic rate. Conjugated linoleic acid effect, enhancing fasting-VO(2)/surface area, postprandial-carbohydrate oxidation and serum lipid hydroperoxide resembled to that of the S group. Conjugated linoleic acid induced cardiac oxidative stress in both fed conditions, and triacylglycerol accumulation in S-CLA rats. Conjugated linoleic acid depressed myocardial LDH comparing C-CLA with C, and beta-hydroxyacyl-coenzyme-A dehydrogenase/CS ratio, comparing S-CLA with S. In conclusion, dietary conjugated linoleic acid supplementation for weight loss can have long-term effects on cardiac health. Conjugated linoleic acid, isomers c9, t11 and t10, c12c9,t11" and "t10,c12" were changed to "c9, t11" and "t10, c12", respectively. Please check if appropriate.--> presented undesirable pro-oxidant effect and induced metabolic changes in cardiac tissue. Nevertheless, despite its effect on abdominal adiposity in sucrose-rich diet condition, conjugated linoleic acid may be disadvantageous because it can lead to oxidative stress and dyslipidemic profile.


Assuntos
Sacarose Alimentar , Metabolismo Energético/efeitos dos fármacos , Ácido Linoleico/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , 3-Hidroxiacil-CoA Desidrogenases/efeitos dos fármacos , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Gordura Abdominal/efeitos dos fármacos , Animais , Citrato (si)-Sintase/efeitos dos fármacos , Citrato (si)-Sintase/metabolismo , Dislipidemias/etiologia , Isomerismo , L-Lactato Desidrogenase/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Ácido Linoleico/farmacologia , Masculino , Obesidade/tratamento farmacológico , Obesidade/etiologia , Oxidantes/efeitos adversos , Oxidantes/farmacologia , Ratos , Ratos Wistar
10.
Reprod Toxicol ; 35: 137-43, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23099337

RESUMO

The aim of this study was to investigate the effects of caffeine (20 mg/L) intake on cadmium (15 mg/L) accumulation in the rat blood, testes, epididymis and prostate as well as cadmium-induced changes to the antioxidant defense system of the epididymis. Caffeine reduced the cadmium concentration in all tissues analyzed. Meanwhile, cadmium reduced catalase activity and increased superoxide dismutase (SOD) activity in the epididymis. Caffeine increased SOD activity, catalase and glutathione tissue expression and sustains the cadmium's effect on catalase and GSP-Px activity. No differences in the expression of metallothionein and lipid peroxidation were observed among the different treatments in the epididymis. In conclusion, low doses of cadmium alter the antioxidant enzymatic profile of the epididymis, but not induced oxidative lipid damage. Caffeine intake reduces overall cadmium accumulation in the organism and enhances the levels of antioxidant protein expression in the epididymis, thus exerting a protective effect against this metal.


Assuntos
Cádmio/toxicidade , Cafeína/farmacologia , Poluentes Ambientais/toxicidade , Epididimo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Catalase/metabolismo , Epididimo/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peróxidos Lipídicos/metabolismo , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Distribuição Tecidual
11.
Reprod Toxicol ; 39: 40-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23591044

RESUMO

Chronic ethanol intake is associated with sex hormone disturbances, and it is well known that melatonin plays a key role in regulating several reproductive processes. We report the effects of ethanol intake and melatonin treatment (at doses of 100 µg/100 g BW/day) on sex hormones and steroid receptors in the ovaries, oviducts and uteri of ethanol-preferring rats. After 150 days of treatment, animals were euthanized, and tissue samples were harvested to evaluate androgen, estrogen, progesterone and melatonin receptor subunits (AR, ER-α and ER-ß, PRA, PRB and MT1R, respectively). Melatonin decreased estradiol (E2) and increased progesterone (P4) and 6-sulfatoxymelatonin (6-STM), while an ethanol-melatonin combination reduced both P4 and E2. Ovarian AR was not influenced by either treatment, and oviduct AR was reduced after ethanol-melatonin combination. Oviduct ER-α, ER-ß and uterine ER-ß were down-regulated by either ethanol or melatonin. Conversely, ovarian PRA and PRB were positively regulated by ethanol and ethanol-melatonin combination, whereas PRA was down-regulated in the uterus and oviduct after ethanol consumption. MT1R was increased in ovaries and uteri of melatonin-treated rats. Ethanol and melatonin exert opposite effects on E2 and P4, and they differentially regulate the expression of sex steroid receptors in female reproductive tissues.


Assuntos
Estradiol/sangue , Etanol/administração & dosagem , Melatonina/administração & dosagem , Progesterona/sangue , Receptores de Esteroides/metabolismo , Alcoolismo/metabolismo , Animais , Feminino , Melatonina/análogos & derivados , Melatonina/sangue , Melatonina/urina , Ovário/efeitos dos fármacos , Ovário/metabolismo , Oviductos/efeitos dos fármacos , Oviductos/metabolismo , Ratos , Útero/efeitos dos fármacos , Útero/metabolismo
12.
Food Chem Toxicol ; 50(10): 3556-61, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22809473

RESUMO

We reported the effects of quercetin on metabolic and hormonal profile as well as serum antioxidant activities in a model of MSG (monosodium glutamate)-induced obesity. Rats were divided into 4 groups: MSG group, submitted to neonatal treatment with high doses of MSG, administrated subcutaneously during 10 days, from 2 day-old; control groups, which received the same volume of saline. After completing 30 day-old, these groups were subdivided into 4 groups: control and MSG groups treated and non-treated with quercetin at doses of 75 mg/kg body weight (i.p.) over 42 days. BW gain and food consumption were higher in MSG treated rats and quercetin significantly reduced BW by 25%. While MSG increased triacylglycerol, total cholesterol and fractions, and reduced HDL concentrations, administration of quercetin normalized HDL-cholesterol and reduced others lipids. Insulin, leptin, glucose and creatinine levels were raised in MSG-treated rats and reduced after quercetin treatment. Alanine transaminase, aspartate transaminase, lactate dehydrogenase and alkaline phosphatase activities were lower after MSG-quercetin combination compared to rats given only MSG. MSG-quercetin combination augmented total protein and urea levels as well as glutathione peroxidase and superoxide dismutase activities in contrast to MSG-treated animals. Quercetin normalized serum lipid and glucose profile and minimized the MSG-related toxic effects, which was associated to its antioxidant properties.


Assuntos
Antioxidantes/metabolismo , Glicemia , Metabolismo dos Lipídeos/efeitos dos fármacos , Quercetina/farmacologia , Glutamato de Sódio/toxicidade , Animais , Proteínas Sanguíneas/metabolismo , Masculino , Ratos , Aumento de Peso/efeitos dos fármacos
13.
Obesity (Silver Spring) ; 18(9): 1754-61, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20035275

RESUMO

The purpose of the present study was to determine calorimetric parameters to predict obesity adverse effects on oxidative stress and cardiac energy metabolism. Male Wistar 24 rats were divided into three groups (n = 8): given standard chow and water (C), receiving standard chow and 30% sucrose in its drinking water (S), and given sucrose-rich diet and water (SRD). After 45 days, both S and SRD rats had obesity, serum oxidative stress, and dyslipidemic profile, but the body weight gain and feed efficiency (FE) were higher in SRD than in S, whereas the obesity-related oxidative stress, myocardial triacylglycerol accumulation, and enhanced cardiac lactate dehydrogenase (LDH) activity were higher in S than in SRD rats. Myocardial beta-hydroxyacyl coenzyme-A-dehydrogenase was lower in SRD and in S than in C, whereas glycogen was only depleted in S rats. Myocardial pyruvate dehydrogenase (PDH) was lowest in S rats indicating depressed glucose oxidation. There was higher myocardial LDH/citrate synthase (CS) ratio and lower adenosine triphosphate (ATP)-synthetase indicating delayed aerobic metabolism in S rats than in the others. Cardiac ATP-synthetase was positively correlated with energy expenditure, namely resting metabolic rate (RMR), and with oxygen consumption per body weight (VO(2)/body weight). Myocardial lipid hydroperoxide (LH)/ total antioxidant substances (TAS) ratio and triacylglycerol accumulation were negatively correlated with RMR and with VO(2)/body weight. In conclusion, the present study brought new insights into obesity because the study demonstrated for the first time that reduced energy expenditure and oxygen consumption may provide novel risk factors of obesity-induced reduced energy generation for myocardial contractile function. The results serve to highlight the role of calorimetric changes as novel biomarkers of risk to obesity-induced cardiac effects.


Assuntos
Sacarose Alimentar/farmacologia , Metabolismo Energético , Enzimas/metabolismo , Cardiopatias/metabolismo , Miocárdio/metabolismo , Obesidade/complicações , Consumo de Oxigênio , Complexos de ATP Sintetase/metabolismo , Animais , Antioxidantes/metabolismo , Metabolismo Basal , Biomarcadores/metabolismo , Glicemia/metabolismo , Citrato (si)-Sintase/metabolismo , Glicogênio/metabolismo , Coração/efeitos dos fármacos , Cardiopatias/etiologia , Peróxidos Lipídicos/metabolismo , Masculino , Oxirredução , Estresse Oxidativo , Oxirredutases/metabolismo , Ratos , Ratos Wistar , Triglicerídeos/metabolismo , Aumento de Peso/efeitos dos fármacos
14.
Growth Horm IGF Res ; 20(2): 149-55, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20060348

RESUMO

OBJECTIVE: This study evaluated the effects of growth hormone (GH) on morphology and myogenic regulatory factors (MRF) gene expression in skeletal muscle of rats with ascending aortic stenosis (AAS) induced chronic heart failure. DESIGN: Male 90-100g Wistar rats were subjected to thoracotomy. AAS was created by placing a stainless-steel clip on the ascending aorta. Twenty five weeks after surgery, rats were treated with daily subcutaneous injections of recombinant human GH (2mg/kg/day; AAS-GH group) or saline (AAS group) for 14 days. Sham-operated animals served as controls. Left ventricular (LV) function was assessed before and after treatment. IGF-1 serum levels were measured by ELISA. After anesthesia, soleus muscle was frozen in liquid nitrogen. Histological sections were stained with HE and picrosirius red to calculate muscle fiber cross-sectional area and collagen fractional area, respectively. MRF myogenin and MyoD expression was analyzed by reverse transcription PCR. RESULTS: Body weight was similar between groups. AAS and AAS-GH groups presented dilated left atrium, left ventricular (LV) hypertrophy (LV mass index: Control 1.90+/-0.15; AAS 3.11+/-0.44; AAS-GH 2.94+/-0.47 g/kg; p<0.05 AAS and AAS-GH vs. Control), and reduced LV posterior wall shortening velocity. Soleus muscle fiber area was significantly lower in AAS than in Control and AAS-GH groups; there was no difference between AAS-GH and Control groups. Collagen fractional area was significantly higher in AAS than Control; AAS-GH did not differ from both Control and AAS groups. Serum IGF-1 levels decreased in AAS compared to Control. MyoD mRNA was significantly higher in AAS-GH than AAS; there was no difference between AAS-GH and Control groups. Myogenin mRNA levels were similar between groups. CONCLUSION: In rats with aortic stenosis-induced heart failure, growth hormone administration increases MyoD gene expression above non-treated animal levels, preserves muscular trophism and attenuates interstitial fibrosis. These results suggest that growth hormone may have a potential role as an adjuvant therapy for chronic heart failure.


Assuntos
Hormônio do Crescimento/farmacologia , Insuficiência Cardíaca/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Animais , Doença Crônica , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Ecocardiografia , Expressão Gênica/efeitos dos fármacos , Insuficiência Cardíaca/sangue , Fator de Crescimento Insulin-Like I/análise , Masculino , Proteína MyoD/genética , Proteína MyoD/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Placebos , Distribuição Aleatória , Ratos , Ratos Wistar
15.
Int J Cardiol ; 124(1): 92-9, 2008 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-17383755

RESUMO

BACKGROUND: Diet compounds may influence obesity-related cardiac oxidative stress and metabolic sifting. Carbohydrate-rich diet may be disadvantageous from fat-rich diet to cardiac tissue and glycemic index rather than lipid profile may predict the obesity-related cardiac effects. MATERIALS AND METHODS: Male Wistar rats were divided into three groups (n=8/group): (C) receiving standard chow (3.0 kcal/g); (CRD) receiving carbohydrate-rich diet (4.0 kcal/g), and (FRD) receiving fat-rich diet (4.0 kcal/g). Rats were sacrificed after the oral glucose tolerance test (OGTT) at 60 days of dietary treatments. Lipid profile and oxidative stress parameters were determined in serum. Myocardial samples were used to determine oxidative stress, metabolic enzymes, glycogen and triacylglycerol. RESULTS: FRD rats showed higher final body weight and body mass index than CRD and C. Serum cholesterol and low-density lipoprotein were higher in FRD than in CRD, while triacylglycerol and oxidized low-density lipoprotein cholesterol were higher in CRD than in FRD. CRD rats had the highest myocardial lipid hydroperoxide and diminished superoxide dismutase and catalase activities. Myocardial glycogen was lower and triacylglycerol was higher in CRD than in C and FRD rats. Although FRD rats had depressed myocardial-reducing power, no significant changes were observed in myocardial energy metabolism. Myocardial beta-hydroxyacyl coenzyme-A dehydrogenase and citrate synthase, as well as the enhanced lactate dehydrogenase/citrate synthase ratio indicated that fatty acid degradation was decreased in CRD rats. Glycemic index was positively correlated with obesity-related cardiac effects. CONCLUSIONS: Isoenergetic carbohydrate-rich and fat-rich diets induced different degree of obesity and differently affected lipid profile. Carbohydrate-rich diet was deleterious relative to fat-rich diet in the heart enhancing lipoperoxidation and shifting the metabolic pathway for energy production. Glycemic index rather than dyslipidemic profile may predict the obesity effects on cardiac tissue.


Assuntos
Dieta , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Miocárdio/metabolismo , Obesidade/metabolismo , Análise de Variância , Animais , Índice de Massa Corporal , Metabolismo Energético/fisiologia , Teste de Tolerância a Glucose , Índice Glicêmico , Glicogênio/metabolismo , Metabolismo dos Lipídeos , Lipídeos/sangue , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Triglicerídeos/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA