RESUMEN
Our current investigation comprises the synthesis and pharmacological impact of bromelain copper nanoparticles (BrCuNP) against diabetes mellitus (DM) and associated ischemia/reperfusion (I/R) - induced myocardial infarction. Bromelain is a proteolytic enzyme obtained from Ananas comosus L. Merr., which has blood platelet aggregation inhibiting and arterial thrombolytic potential. Moreover, copper is well-known to facilitate glucose metabolism and strengthen cardiac muscle and antioxidant activity; although, chronic or long-term exposure to high doses of copper may lead to copperiedus. To restrict these potential hazards, we synthesized herbal nano-formulation which convincingly indicated the improved primordial therapeutic potential of copper by reformulating the treatment carrier with bromelain, resulting in facile synthesis of BrCuNP. DM was induced by administration of double cycle repetitive dose of low dose streptozotocin (20 mg/kg, i.p.) in high-fat diet- fed animals. DM and associated myocardial I/R injury were estimated by increased serum levels of total cholesterol, low-density lipoprotein, very low-density lipoprotein, lactate dehydrogenase, creatine kinase myocardial band, cardiac troponin, thiobarbituric acid reactive substances, tumor necrosis factor α, interleukin 6, and reduced serum level of high-density lipoprotein and nitrite/nitrate concentration. However, treatment with BrCuNP ameliorates various serum biomarkers by approving cardioprotective potential against DM- and I/R-associated injury. Furthermore, upturn of histopathological changes were observed in cardiac tissue of BrCuNP-treated rats in comparison to disease models.
Asunto(s)
Bromelaínas/síntesis química , Bromelaínas/uso terapéutico , Cobre/química , Cobre/uso terapéutico , Complicaciones de la Diabetes/complicaciones , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/etiología , Daño por Reperfusión Miocárdica/complicaciones , Animales , Bromelaínas/farmacología , Cobre/farmacología , Modelos Animales de Enfermedad , Femenino , Ratas WistarRESUMEN
INTRODUCTION: Introduction The impact of lameness on milk yield in dairy cows has been investigated already in many countries by several authors, taking into consideration almost exclusively locomotion scores ≥ 3. The aim of this study was to evaluate the impact of lameness and of the various lameness scores (2-5) on milk yield and milk solids in cows of the three most important dairy cattle breeds (Fleckvieh, Braunvieh, Holstein-Friesian) in Austria within one lactation period. Material and methods Locomotion scoring of dairy cows was performed by trained personnel every 30-40 days in 2014 during the course of routine performance testing. From the recorded locomotion scores (1-5) and the number of lameness episodes, the cows were classified into five lactation-locomotion-score-groups (LLS-G1-5). In total, data sets of 4005 cows from 144 dairy farms across Austria could be evaluated. Using two statistical models the fixed effects on LLS group, breed (evaluation across all breeds in model 1), farm, year and season of calving, parity and the «continuous effect¼ number of milking days were included in the analyses of milk, fat and protein yield. Results The mean, cumulative lameness prevalence during the observation period was 51.0%, and 8.1% were cows from the LLS-G5 group showing repeated and severe locomotion scores. During the first 100 days in milk 34.7% of all cows were lame. In model 1, all effects considered had a significant impact (P .
INTRODUCTION: Introduction L'impact des boiteries sur le rendement laitier des vaches a déjà été étudié dans de nombreux pays par plusieurs auteurs, en prenant en compte presque exclusivement des scores de locomotion ≥ 3. Le but de cette étude était d'évaluer l'impact de la boiterie et des différents scores de boiterie (25) sur le rendement laitier et la matière sèche du lait chez les vaches des trois races bovines laitières les plus importantes (Fleckvieh, Braunvieh, Holstein-Friesian) en Autriche au cours d'une période de lactation. Matériel et méthode Le scoring de locomotion des vaches laitières a été effectué par du personnel formé tous les 30 à 40 jours en 2014 au cours des tests de performance de routine. À partir des scores de locomotion enregistrés (15) et du nombre d'épisodes de boiterie, les vaches ont été classées en cinq groupes de score de lactation-locomotion (LLS-G15). Au total les données de 4 005 vaches provenant de 144 exploitations laitières de toute l'Autriche ont pu être évaluées. À l'aide de deux modèles statistiques, les effets fixes sur le groupe LLS, la race (évaluation pour toutes les races dans le modèle 1), l'exploitation, l'année et la saison de vêlage, le nombre de lactations et le nombre de jours de traite par rapport aux analyses des quantités de lait, des matières grasses et des protéines ont été pris en compte. Résultats La prévalence moyenne cumulative de boiteries pendant la période d'observation était de 51,0% et 8,1% étaient des vaches du groupe LLS-G5 présentant des boiteries répétées et sévères. Au cours des 100 premiers jours de lactation, 34,7% de toutes les vaches étaient boiteuses. Dans le modèle 1, tous les effets considérés de manière significative (P .
Asunto(s)
Bovinos/fisiología , Lactancia , Cojera Animal/fisiopatología , Animales , Austria/epidemiología , Industria Lechera , Femenino , Lactancia/fisiología , Cojera Animal/epidemiología , Leche/química , PrevalenciaRESUMEN
N-acetylcysteine (NAC) and melatonin were reported to exert protective effects on testicular tissues. Thus, this study aimed to determine which of these is more efficient against obesity-induced testicular dysfunction in albino rats. A total of 32 adult male rats (195 ± 10 g) were divided into four groups: control, obese rats fed a high-fat diet (HFD), HFD+NAC (150 mg/kg per day, i.p.) and HFD+melatonin (10 mg/kg per day, i.p.), for 5 weeks. Testes and epididymis were weighed. Lipid profile, pituitary-testicular hormones, tumor necrosis factor α (TNFα), epididymal sperm parameters, testicular oxidant-antioxidant system, testicular and the epididymal histopathology and immunohistochemical localization for androgen receptors (AR) and Bax reaction were analyzed. Administration of NAC or melatonin significantly improved the lipid parameters, gonadal hormones, TNFα level, sperm count and abnormal morphology, oxidant-antioxidant system and the absolute testicular and epididymal mass with an enhancement of testicular architecture, AR expression and apoptosis as compared with that in the obese group. Additionally, as compared with the NAC group, the melatonin group had significantly reduced body mass index, total cholesterol, triglyceride, and TNFα and increased testosterone, sperm count, motility, superoxide dismutase activity, mitigated histomorphometrical changes, Bax expression, and increased testicular AR expression. Therefore, melatonin was more efficient than NAC in affording fortification against HFD-induced testicular dysfunction.
Asunto(s)
Acetilcisteína , Melatonina , Testículo , Animales , Epidídimo , Masculino , Estrés Oxidativo , RatasRESUMEN
OBJECTIVES: Inadequate nutrient supply and insulin resistance contribute to the pathogenesis of metabolic syndrome (MetS) and increase the risk of developing cardiovascular disease. MetS can be induced by prolonged feeding of a high-carbohydrate, high-fat (HCHF) diet. The present study was designed using Wistar albino rats as an experimental model to investigate the effect of subchronic withdrawal of an HCHF diet during MetS on distribution of copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), zinc (Zn) and chromium (Cr) in different biological media. METHODS: The experimental animals were fed an HCHF diet for up to 16 weeks for induction of MetS. After inducing MetS, some animals were shifted to a basal diet for the next 4 weeks. Distribution of trace elements (TE) in serum, liver and faeces at the different time intervals and their relationship with dietary TE were analyzed. RESULTS: On withdrawal of the HCHF diet, concentrations of Zn, Mg, Mn (serum, p<0.05; liver, p<0.001) and Cr were increased, and Cu and Fe were decreased in serum and liver at week 16. Furthermore, levels of Cu and Fe were reduced significantly (p<0.05) in faeces on feeding the HCHF diet and increased on withdrawal of the diet, which also reflects the metabolic fate of TE during MetS. CONCLUSIONS: Consumption of an HCHF diet over a long time period leads to alteration of the TE profile in serum, liver and feces during MetS, which is reversed upon dietary intervention. This can be correlated with their concentrations in HCHF and basal diets, and hence can contribute to proper dietary control of this global issue.
Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Dieta Alta en Grasa/estadística & datos numéricos , Carbohidratos de la Dieta/administración & dosificación , Síndrome Metabólico/prevención & control , Oligoelementos/metabolismo , Privación de Tratamiento/estadística & datos numéricos , Animales , Antioxidantes/metabolismo , Modelos Animales de Enfermedad , Resistencia a la Insulina , Masculino , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Síndrome Metabólico/patología , Estrés Oxidativo , Ratas , Ratas WistarRESUMEN
Ingestion of ketone supplements, caffeine, and medium-chain triglycerides (MCTs) may all be effective strategies to increase blood levels of the ketone body beta-hydroxybutyrate (D-BHB). However, acute ingestion of a bolus of lipids may increase oxidative stress (OS). The purpose of the study was to investigate the impact of adding varying amounts of MCTs to coffee on blood levels of D-BHB and markers of OS. Ten college-aged men ingested coffee with 0, 28, and 42 g of MCT in a randomized order. Blood samples were collected pre- as well as 2 and 4 h postprandial and analyzed for D-BHB, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), glucose, triglycerides (TAG), insulin, and OS markers: advanced oxidation protein products (AOPP), glutathione (GSH), malondialdehyde (MDA), and hydrogen peroxide (H2O2). All three treatments resulted in a significant increase in D-BHB, HDL-c, and TC as well as a significant decrease in TAG, MDA, H2O2, and insulin. The 42 g treatment was associated with significantly higher levels of AOPP and MDA. Acute ingestion of coffee results in favorable changes to markers of cardiometabolic health that were not impacted by the addition of 28 g of MCT. However, 42 g of MCT caused significantly greater OS.
Asunto(s)
Biomarcadores/sangre , Café/metabolismo , Ingestión de Alimentos/fisiología , Cetonas/sangre , Estrés Oxidativo/fisiología , Triglicéridos/sangre , Adulto , Biomarcadores/metabolismo , Glucemia/metabolismo , HDL-Colesterol/sangre , Suplementos Dietéticos , Método Doble Ciego , Glucosa/metabolismo , Humanos , Peróxido de Hidrógeno/metabolismo , Insulina/sangre , Masculino , Malondialdehído/metabolismo , Periodo Posprandial/fisiología , Adulto JovenRESUMEN
Dronedarone biodistribution in hyperlipidemia and dronedarone metabolism in hyperlipidemia or obesity were assessed. Male Sprague-Dawley rats were given either normal standard chow with water or various high-fat or high-carbohydrate diets for 14 weeks. There was also a nonobese hyperlipidemic group given poloxamer 407 intraperitoneally. Liver and intestinal microsomes were prepared and the metabolic conversion of dronedarone to desbutyldronedarone was followed. A biodistribution study of dronedarone given orally was conducted in hyperlipidemic and control normolipidemic rats. The metabolism of dronedarone to desbutyldronedarone in control rats was consistent with substrate inhibition. However in the treatment groups, the formation of desbutyldronedarone did not follow substrate inhibition; hyperlipidemia and high-calorie diets created remarkable changes in dronedarone metabolic profiles and reduction in formation velocities. Tissue concentrations of dronedarone were much higher than in plasma. Furthermore, in hyperlipidemia, plasma and lung dronedarone concentrations were significantly higher compared to normolipidemia.
Asunto(s)
Antiarrítmicos/metabolismo , Dieta Alta en Grasa/efectos adversos , Dronedarona/metabolismo , Hiperlipidemias/metabolismo , Obesidad/complicaciones , Animales , Antiarrítmicos/administración & dosificación , Dronedarona/administración & dosificación , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/etiología , Hiperlipidemias/patología , Masculino , Obesidad/patología , Ratas , Ratas Sprague-Dawley , Distribución TisularRESUMEN
Oxidative stress is involved in the development of various cancers. In the present study, the effect of long-term administration of peroral antidiabetic metformin and pineal hormone melatonin on liver antioxidant and aerobic status in female Sprague-Dawley rats carrying mammary tumors induced by N-methyl-N-nitrosourea was evaluated. Both substances were administered in a preventive and curative manner (12 days before and 16 weeks after the carcinogen application). Carcinogen administration induced oxidative stress: the level of thiobarbituric acid reactive substances (TBARS) considered as a marker of reactive oxygen species (ROS) generation in liver increased as well as the level of oxidatively modified protein content (OMP; aldehyde and ketone derivates). Metformin administration restored succinate dehydrogenase and lactate dehydrogenase activity and associated ROS production and OMP content to the level of intact rats, with predominant activation of superoxide dismutase (SOD) and glutathione reductase (GR). Melatonin alone and in combination with metformin also decreased TBARS content. OMP content decreased in all groups receiving chemoprevention. The rise in total antioxidant capacity after melatonin and particularly metformin and melatonin combination might result from the initiation of anaerobic metabolism and increasing SOD, GR, and glutathione peroxidase activity. Long-term administration of metformin and melatonin exerts antioxidant properties in liver, especially in combination.
Asunto(s)
Antioxidantes/metabolismo , Carcinogénesis/patología , Hígado/metabolismo , Neoplasias Mamarias Animales/tratamiento farmacológico , Melatonina/administración & dosificación , Melatonina/uso terapéutico , Metformina/administración & dosificación , Metformina/uso terapéutico , Aerobiosis , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Carcinogénesis/efectos de los fármacos , Dieta Alta en Grasa , Femenino , L-Lactato Deshidrogenasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Masculino , Neoplasias Mamarias Animales/sangre , Neoplasias Mamarias Animales/patología , Melatonina/farmacología , Metformina/farmacología , Oxidación-Reducción , Ratas Sprague-Dawley , Succinato Deshidrogenasa/metabolismo , Triglicéridos/sangreRESUMEN
Targeting peroxisome proliferator-activated receptor-gamma (PPAR-γ) is an approved strategy in facing insulin resistance (IR) for diabetes mellitus (DM) type 2. The PPAR-γ modulators display improvements in the insulin-sensitizing and adverse effects of the traditional thiazolidinediones. Nitazoxanide (NTZ) is proposed as a PPAR-γ receptor ligand with agonistic post-transcriptional effects. Currently, NTZ antidiabetic activities versus pioglitazone (PIO) in a high-fat diet/streptozotocin rat model of type 2 diabetes was explored. Diabetic adult male Wistar rats were treated orally with either PIO (2.7 mg·kg-1·day-1) or NTZ (200 mg·kg-1·day-1) for 14, 21, and 28 days. Body masses, fasting blood glucose, IR, lipid profiles, and liver and kidney functions of rats were assayed. Hepatic glucose metabolism and PPAR-γ protein expression levels as well as hepatic, pancreatic, muscular, and renal histopathology were evaluated. Significant time-dependent euglycemic and insulin-sensitizing effects with preservation of liver and kidney functions were offered by NTZ. Higher hepatic levels of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase enzymes and PPAR-γ protein expressions were acquired by NTZ and PIO, respectively. NTZ could be considered an oral therapeutic strategy for DM type 2. Further systematic NTZ/PPAR-γ receptor subtype molecular activations are recommended. Simultaneous use of NTZ with other approved antidiabetics should be explored.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , PPAR gamma/metabolismo , Animales , Glucemia/metabolismo , Tamaño Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/etiología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Ayuno/sangre , Regulación de la Expresión Génica/efectos de los fármacos , Resistencia a la Insulina , Riñón/efectos de los fármacos , Riñón/patología , Riñón/fisiopatología , Hígado/efectos de los fármacos , Hígado/patología , Hígado/fisiopatología , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
The percentage of women who are obese at the time of conception or during pregnancy is increasing, with animal and human studies demonstrating that offspring born to obese dams or mothers are at increased risk for obesity and the metabolic syndrome. Our goal was to confirm in an experimental model of metabolic syndrome in the dam, whether the offspring would be at increased risk of obesity. Conversely, we observed that male offspring born to dams with metabolic syndrome had no alterations in their body mass profiles, whereas female offspring born to dams with metabolic syndrome were heavier at weaning, but exhibited no perturbations in energy metabolism. Moreover, they gained weight at a reduced rate versus female offspring born to healthy dams, and thus weighed less at study completion. Hence, our findings suggest that factors other than increased adiposity and insulin resistance during pregnancy are responsible for the increased risk of obesity in children born to obese mothers.
Asunto(s)
Crecimiento y Desarrollo , Resistencia a la Insulina , Síndrome Metabólico/complicaciones , Obesidad/complicaciones , Adiposidad , Animales , Animales Recién Nacidos , Glucemia/metabolismo , Peso Corporal , Dieta Alta en Grasa , Metabolismo Energético , Femenino , Homeostasis , Ratones Endogámicos C57BL , Obesidad/patología , Factores de Riesgo , Destete , Aumento de Peso/efectos de los fármacosRESUMEN
Hydrogen sulfide (H2S) is synthesized in perivascular adipose tissue (PVAT) and induces vasorelaxation. We examined whether the sulfur-containing AMP and GMP analogs AMPS and GMPS can serve as the H2S donors in PVAT. H2S production by isolated rat periaortic adipose tissue (PAT) was measured with a polarographic sensor. In addition, phenylephrine-induced contractility of aortic rings with (+) or without (-) PAT was examined. Isolated PAT produced H2S from AMPS or GMPS in the presence of the P2X7 receptor agonist BzATP. Phenylephrine-induced contractility of PAT(+) rings was lower than of PAT(-) rings. AMPS or GMPS had no effect on the contractility of PAT(-) rings, but used together with BzATP reduced the contractility of PAT(+) rings when endogenous H2S production was inhibited with propargylglycine. A high-fat diet reduced endogenous H2S production by PAT. Interestingly, AMPS and GMPS were converted to H2S by PAT of obese rats, and reduced contractility of PAT(+) aortic rings isolated from these animals even in the absence of BzATP. We conclude that (i) AMPS and GMPS can be hydrolyzed to H2S by PAT when P2X7 receptors are activated, (ii) a high-fat diet impairs endogenous H2S production by PAT, (iii) AMPS and GMPS restore the anticontractile effects of PAT in obese animals without P2X7 stimulation.