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1.
Life (Basel) ; 13(8)2023 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-37629513

RESUMEN

Certain limitations exist for animals to modify fatty acid changes. Besides the role of arachidonic acid (AA), docosahexaenoic acid (DHA) and other 20-carbon long-chain polyunsaturated fatty acids (LCPUFAs) for the synthesis of inflammatory mediators as eicosanoids, different LCPUFAs have many other effects, including their abilities to regulate gene expression and downstream events. LCPUFAs are susceptible to autoxidation, which is prevented by the action of antioxidants in the form of enzymes like superoxide dismutases, catalases and peroxidases, as well as antioxidant compounds that protect against oxidation or repair the damage caused. Under normal conditions, the fetus needs both essential fatty acids (EFAs) and LCPUFAs, which are obtained from its mother by placental transfer. In early pregnancy, dietary derived fatty acids are accumulated in maternal adipose tissue. However, during late pregnancy, corresponding to the period of the highest fetal growth, maternal adipose tissue becomes catabolic and LCPUFAs are released into the circulation by adipose lipolytic activity. The released LCPUFAs are taken up by maternal liver to be esterified and released back to the circulation as triacylglycerides (TAGs) in very-low-density lipoprotein (VLDL) that become available to the placenta to be transferred to the fetus in the form of non-esterified fatty acids (NEFAs). An enhanced adipose tissue lipolysis is maintained around parturition and esterified LCPUFAs are diverted to mammary glands thanks to an increased activity of lipoprotein lipase for milk production. Throughout this process, LCPUFAs become available to the newborn during suckling. The important role of both DHA and AA for the development of the nervous system and for growth has motivated their dietary supplement during different postnatal stages. This has been especially important in preterm infants both because under normal conditions, the fetus acquires most of these fatty acids during late pregnancy, and because the immaturity of the enzyme systems for the synthesis of AA and DHA from their respective EFAs.

2.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-34638763

RESUMEN

Maternal obesity in pregnancy is a pro-inflammatory condition exposing the fetus to an adverse environment. Here, we tested associations of maternal obesity (primary exposures: BMI, leptin) and metabolic parameters (secondary exposures: glucose, C-peptide, and insulin sensitivity) with total serum concentrations of fatty acids in the first trimester of human pregnancy. This cross-sectional study included 123 non-smoking women with singleton pregnancy. In maternal serum, cotinine, leptin, and C-peptide (ELISA), glucose (hexokinase-based test) and fatty acids (gas chromatography) were quantified, and the insulin sensitivity index (ISHOMA) was calculated. Concentrations of fatty acid classes and total fatty acids did not differ between BMI or leptin categories. However, n-3 polyunsaturated fatty acids (PUFA) were decreased in the category with the highest C-peptide concentration (n-3 PUFA: CI -35.82--6.28, p < 0.006) and in the lowest ISHOMA category (n-3 PUFA: CI -36.48--5.61, p < 0.008). In a subcohort, in which fetal sex was determined (RT-qPCR of placental tissue), C-peptide was significantly associated with docosahexaenoic acid (DHA) in mothers bearing a female (n = 46), but not male (n = 37) fetus. In conclusion, pregnant women with high fasting C-peptide and low ISHOMA had decreased n-3 PUFA, and DHA was lower with higher C-peptide only in mothers bearing a female fetus.


Asunto(s)
Índice de Masa Corporal , Péptido C/sangre , Ácidos Grasos Omega-3/sangre , Resistencia a la Insulina , Obesidad Materna/sangre , Primer Trimestre del Embarazo/sangre , Adulto , Estudios Transversales , Femenino , Humanos , Embarazo
3.
J Mech Behav Biomed Mater ; 112: 104013, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32846285

RESUMEN

Chronic hypoxia is a condition that increases the cardiovascular complications of newborns gestated and born at high altitude (HA), over 2500 m above sea level (masl). A particularly complex pathology is pulmonary arterial hypertension of the neonate (PHN), which is increased at HA due to hypobaric hypoxia. Basic and clinical research have recognized that new treatments are needed, because current ones are, in general, palliative and with low effectiveness. Therefore, recently we have proposed melatonin as a potential adjuvant treatment to improve cardiopulmonary function. However, melatonin effects on the mechanical response of the arteries and their microstructure are not known. This study assesses the effects of a neonatal treatment with daily low doses of melatonin on the passive biomechanical behavior of the aorta artery and main pulmonary artery of PHN lambs born in chronic hypobaric hypoxia (at 3600 masl). With this purpose, ex-vivo measurements were made on axial stretch, tensile and opening ring tests together with a histological analysis to explore the morphometry and microstructure of the arteries. Our results show that the passive mechanical properties of the aorta artery and main pulmonary artery of lambs do not seem to be affected by a treatment based on low melatonin doses. However, we found evidence that melatonin has microstructural effects, particularly, diminishing cell proliferation, which is an indicator of antiremodeling capacity. Therefore, the use of melatonin as an adjuvant against pathologies like PHN would present antiproliferative effect at the microstructural level, keeping the macroscopic properties of the aorta artery and main pulmonary artery.


Asunto(s)
Hipertensión Pulmonar , Hipoxia , Melatonina , Animales , Animales Recién Nacidos , Hipertensión Pulmonar/tratamiento farmacológico , Hipoxia/tratamiento farmacológico , Melatonina/farmacología , Arteria Pulmonar , Ovinos
5.
Food Chem Toxicol ; 123: 546-552, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30543894

RESUMEN

We studied in rats the effects of cafeteria diet (CD) supplemented (or not) with fish oil (FO) during just the first 12 days of pregnancy, or during the whole of pregnancy and lactation in 14-month old offspring. Female rats were given standard diet (STD) or CD and after mating some animals remained on STD or CD; for some CD rats the diet was supplemented with 8.78% FO. After 12 days, half of the CD-FO group returned to CD (CD-FO12) and the others remained on CD-FO. From weaning all offspring were given STD. The adiposity index of male offspring of CD dams increased but was normal in CD-FO males. Plasma triacylglycerols (TAG) and individual fatty acid concentrations were similar among the groups. Liver total lipids, TAG, fatty acid concentrations, Δ9-desaturase indices and the mRNA expression of fatty acid synthase were higher in male offspring of CD than in those of STD; most of these differences disappeared in male offspring of CD-FO12 and CD-FO dams. Female offspring showed smaller changes. Thus, a moderate supplement with FO during just the first half of gestation or during pregnancy and lactation in rats on CD decreases the liver steatosis in male adult offspring.


Asunto(s)
Dieta/efectos adversos , Suplementos Dietéticos/análisis , Hígado Graso/prevención & control , Aceites de Pescado/administración & dosificación , Efectos Tardíos de la Exposición Prenatal/prevención & control , Animales , Ácidos Grasos/sangre , Hígado Graso/sangre , Hígado Graso/etiología , Femenino , Humanos , Hígado/metabolismo , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/etiología , Ratas , Ratas Sprague-Dawley , Factores Sexuales , Triglicéridos/sangre
6.
Oxid Med Cell Longev ; 2018: 7239123, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29576853

RESUMEN

Alterations in cardiac energy metabolism play a key role in the pathogenesis of diabetic cardiomyopathy. Hypercholesterolemia associated with bioenergetic impairment and oxidative stress has not been well characterized in the cardiac function under glycemic control deficiency conditions. This work aimed to determine the cardioprotective effects of quercetin (QUE) against the damage induced by a high-cholesterol (HC) diet in hyperglycemic rats, addressing intracellular antioxidant mechanisms and bioenergetics. Quercetin reduced HC-induced alterations in the lipid profile and glycemia in rats. In addition, QUE attenuated cardiac diastolic dysfunction (increased E:A ratio), prevented cardiac cholesterol accumulation, and reduced the increase in HC-induced myocyte density. Moreover, QUE reduced HC-induced oxidative stress by preventing the decrease in GSH/GSSG ratio, Nrf2 nuclear translocation, HO-1 expression, and antioxidant enzymatic activity. Quercetin also counteracted HC-induced bioenergetic impairment, preventing a reduction in ATP levels and alterations in PGC-1α, UCP2, and PPARγ expression. In conclusion, the mechanisms that support the cardioprotective effect of QUE in rats with HC might be mediated by the upregulation of antioxidant mechanisms and improved bioenergetics on the heart. Targeting bioenergetics with QUE can be used as a pharmacological approach to modulate structural and functional changes of the heart under hypercholesterolemic and hyperglycemic conditions.


Asunto(s)
Dieta/efectos adversos , Soplos Cardíacos/prevención & control , Hipercolesterolemia/tratamiento farmacológico , Quercetina/farmacología , Animales , Colesterol/administración & dosificación , Metabolismo Energético , Soplos Cardíacos/tratamiento farmacológico , Soplos Cardíacos/etiología , Hipercolesterolemia/patología , Hiperglucemia/etiología , Hiperglucemia/fisiopatología , Masculino , Estrés Oxidativo , Distribución Aleatoria , Ratas , Ratas Wistar
7.
Eur J Nutr ; 57(8): 2963-2974, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29127477

RESUMEN

PURPOSE: The utilization of long-chain polyunsaturated fatty acids (LCPUFA) by the fetus may exceed its capacity to synthesize them from essential fatty acids, so they have to come from the mother. Since adipose tissue lipolytic activity is greatly accelerated under fasting conditions during late pregnancy, the aim was to determine how 24 h fasting in late pregnant rats given diets with different fatty acid compositions affects maternal and fetal tissue fatty acid profiles. METHODS: Pregnant Sprague-Dawley rats were given isoenergetic diets containing 10% palm-, sunflower-, olive- or fish-oil. Half the rats were fasted from day 19 of pregnancy and all were studied on day 20. Triacylglycerols (TAG), glycerol and non-esterified fatty acids (NEFA) were analyzed by enzymatic methods and fatty acid profiles were analyzed by gas chromatography. RESULTS: Fasting caused increments in maternal plasma NEFA, glycerol and TAG, indicating increased adipose tissue lipolytic activity. Maternal adipose fatty acid profiles paralleled the respective diets and, with the exception of animals on the olive oil diet, maternal fasting increased the plasma concentration of most fatty acids. This maintains the availability of LCPUFA to the fetus during brain development. CONCLUSIONS: The results show the major role played by maternal adipose tissue in the storage of dietary fatty acids during pregnancy, thus ensuring adequate availability of LCPUFA to the fetus during late pregnancy, even when food supply is restricted.


Asunto(s)
Tejido Adiposo/química , Ácidos Grasos/química , Feto/química , Fenómenos Fisiologicos Nutricionales Maternos , Animales , Dieta , Grasas de la Dieta/administración & dosificación , Ayuno , Ácidos Grasos no Esterificados/química , Femenino , Aceites de Pescado/administración & dosificación , Lipólisis , Intercambio Materno-Fetal , Aceite de Oliva/administración & dosificación , Embarazo , Ratas , Ratas Sprague-Dawley , Aceite de Girasol/administración & dosificación , Triglicéridos/sangre
8.
PLoS One ; 12(6): e0179785, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28644857

RESUMEN

PURPOSE: The Hibiscus rosa-sinensis flower is widely used in Brazilian traditional medicine for the treatment of diabetes and has shown antifertility activity in female Wistar rats. However, there is no scientific confirmation of its effect on diabetes and pregnancy. The aim of this study was evaluate the effect of aqueous extract of H. rosa-sinensis flowers on maternal-fetal outcome in pregnant rats with diabetes. METHODS: Diabetes was induced by streptozotocin (STZ, 40 mg/kg) in virgin, adult, female Wistar rats. After diabetes induction, the rats were mated. The pregnant rats were distributed into four groups (n minimum = 11 animals/group): non-diabetic, non-diabetic treated, diabetic, and diabetic treated. Oral aqueous extract of Hibiscus rosa-sinensis was administered to rats in the treatment groups during pregnancy. At term pregnancy, maternal reproductive outcomes, fetal parameters, and biochemical parameters were analyzed. RESULTS: The non-diabetic treated group showed decreased high density lipoprotein cholesterol, increased atherogenic index (AI) and coronary artery risk index (CRI), and increased preimplantation loss rate compared to the non-diabetic group. Although treatment with H. rosa-sinensis led to no toxicity, it showed deleterious effects on cardiac and reproductive functions. However, the diabetic treated group showed increased maternal and fetal weights, reduced AI and CRI, and reduced preimplantation loss rate compared to the untreated diabetic group. CONCLUSION: Our results demonstrate beneficial effects of this flower only in pregnant rats with diabetes and their offspring. Although these findings cannot be extrapolated to human clinical use, they show that the indiscriminate intake of H. rosa-sinensis may be harmful to healthy individuals and its use should be completely avoided in pregnancy.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Gestacional/tratamiento farmacológico , Hibiscus , Hipoglucemiantes/farmacología , Fitoterapia , Extractos Vegetales/farmacología , Administración Oral , Animales , HDL-Colesterol/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Gestacional/sangre , Evaluación Preclínica de Medicamentos , Femenino , Flores/química , Hibiscus/química , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/química , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Extractos Vegetales/efectos adversos , Extractos Vegetales/química , Embarazo , Resultado del Embarazo , Distribución Aleatoria , Ratas Wistar , Agua/química
9.
J Nutr Biochem ; 34: 146-55, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27322812

RESUMEN

Dietary microRNAs (miRNAs) modulation could be important for health and wellbeing. Part of the healthful activities of polyphenols might be due to a modulation of miRNAs' expression. Among the most biologically active polyphenols, hydroxytyrosol (HT) has never been studied for its actions on miRNAs. We investigated whether HT could modulate the expression of miRNAs in vivo. We performed an unbiased intestinal miRNA screening in mice supplemented (for 8 weeks) with nutritionally relevant amounts of HT. HT modulated the expression of several miRNAs. Analysis of other tissues revealed consistent HT-induced modulation of only few miRNAs. Also, HT administration increased triglycerides levels. Acute treatment with HT and in vitro experiments provided mechanistic insights. The HT-induced expression of one miRNA was confirmed in healthy volunteers supplemented with HT in a randomized, double-blind and placebo-controlled trial. HT consumption affects specific miRNAs' expression in rodents and humans. Our findings suggest that the modulation of miRNAs' action through HT consumption might partially explain its healthful activities and might be pharmanutritionally exploited in current therapies targeting endogenous miRNAs. However, the effects of HT on triglycerides warrant further investigations.


Asunto(s)
Suplementos Dietéticos , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Leucocitos Mononucleares/metabolismo , MicroARNs/metabolismo , Alcohol Feniletílico/análogos & derivados , Animales , Línea Celular , Células Cultivadas , Estudios Cruzados , Método Doble Ciego , Humanos , Mucosa Intestinal/citología , Intestino Delgado/citología , Masculino , Ratones Endogámicos C57BL , Especificidad de Órganos , Organoides , Alcohol Feniletílico/administración & dosificación , Alcohol Feniletílico/metabolismo , Técnicas de Cultivo de Tejidos
10.
Eur J Nutr ; 55(4): 1741-53, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26195235

RESUMEN

PURPOSE: The aim was to determine the effects of cafeteria diet (CD) and fish oil supplements given to pregnant and lactating rats on the birth weight and fatty acid profiles of their offspring. METHODS: Female rats were given standard diet (STD) or CD for 22 days before pregnancy. After mating, some animals remained on STD or CD; for some CD rats, the diet was supplemented with 8.78 % fish oil (CD-FO). After 12 days, half the CD-FO group returned to CD (CD-FO12) and the others remained on CD-FO. RESULTS: At birth, body weights of pups of the three CD groups were lower than STD, maintained until 21 days in the CD-FO group only. At the end of lactation, dams of the CD groups had increased plasma triacylglycerols (TAG), non-esterified fatty acids, and glycerol concentrations, whereas most n-6 long-chain polyunsaturated fatty acids (LCPUFA) were decreased, the effect being greatest in the CD-FO group, where most n-3 LCPUFA were increased and indices of Δ(5) and Δ(6) desaturase activities decreased. The 21-day-old pups of the CD group had increased plasma TAG, not present in the CD-FO group, which had increased 3-hydroxybutyrate concentrations. In both 2- and 21-day-old CD pups, plasma concentrations of ARA were lower than STD, and even lower in the two CD-FO groups. CONCLUSIONS: The effect of CD and CD-FO decreasing pups body weight could be related to decreased concentrations of ARA, caused by the inhibition of the Δ(5) and Δ(6) desaturases in the pathway of n-6 LCPUFA biosynthesis.


Asunto(s)
Peso Corporal/efectos de los fármacos , Dieta/veterinaria , Aceites de Pescado/farmacología , Lactancia/efectos de los fármacos , Ácido 3-Hidroxibutírico/sangre , Animales , Animales Recién Nacidos , Ácido Araquidónico/sangre , Peso al Nacer/efectos de los fármacos , Grasas de la Dieta/administración & dosificación , Suplementos Dietéticos , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Femenino , Embarazo , Ratas , Ratas Sprague-Dawley , Triglicéridos/sangre
11.
Plant Foods Hum Nutr ; 70(2): 170-5, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25724576

RESUMEN

Blackberry (Rubus sp.) fruit has a high content of anthocyanins, but its health benefits have not been sufficiently explored in healthy individuals. Thus, the aim of the study was to determine the effects of blackberry extract on lipid and glucose variables in female and male rats. Sprague Dawley rats were given a standard pellet (SD) or cafeteria (CD) diet supplemented (SD+R and CD+R) or not with Rubus extract for 80 days. Female rats given SD+R had lower body and liver weights than SD females; both sexes given SD+R showed lower plasma glucose and insulin, higher plasma NEFA, glycerol and 3-hydroxybutyrate, and higher liver concentration of triacylglycerols than SD rats. The homeostasis model of insulin resistance (HOMA) was lower in SD+R rats than in SD rats, but higher in CD rats. No effects of Rubus extract were observed in CD rats. In conclusion, Rubus extract, in rats given SD, decreased glycemia and increased insulin sensitivity. It also increased lipid breakdown in adipose tissue. The effects were greater in females than in males. No effect was seen in rats given CD, probably as a result of their high insulin resistance.


Asunto(s)
Suplementos Dietéticos , Resistencia a la Insulina , Extractos Vegetales/administración & dosificación , Rubus/química , Animales , Glucemia/metabolismo , Colesterol/sangre , Dieta/veterinaria , Femenino , Insulina/sangre , Masculino , Ratas , Ratas Sprague-Dawley , Triglicéridos/sangre
12.
J Pineal Res ; 58(3): 362-73, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25736256

RESUMEN

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial- and muscular-dependent pathways. This was associated with an enhanced nitric oxide-dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.


Asunto(s)
Antioxidantes/farmacología , Hipertensión Pulmonar/metabolismo , Pulmón/efectos de los fármacos , Melatonina/farmacología , Estrés Oxidativo/efectos de los fármacos , Arteria Pulmonar/efectos de los fármacos , Animales , Animales Recién Nacidos , Pulmón/irrigación sanguínea , Arteria Pulmonar/fisiología , Ovinos
13.
Mar Drugs ; 13(2): 838-60, 2015 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-25658050

RESUMEN

Intermittent hypobaric hypoxia (IH) is linked with oxidative stress, impairing cardiac function. However, early IH also activate cardio-protective mechanisms. Omega 3 fatty acids (Ω3) induce cardioprotection by reducing infarct size and reinforcing antioxidant defenses. The aim of this work was to determine the combined effects of IH and Ω3 on cardiac function; oxidative balance and inflammatory state. Twenty-eight rats were randomly divided into four groups: normobaric normoxia (N); N + Ω3 (0.3 g·kg-1·day-1); IH; and IH + Ω3. IH was induced by 4 intercalate periods of hypoxia (4 days)-normoxia (4 days) in a hypobaric chamber during 32 days. At the end of the exposure, hearts were mounted in a Langendorff system and subjected to 30 min of ischemia followed by 120 min of reperfusion. In addition, we determined HIF-1α and ATP levels, as well as oxidative stress by malondialdehyde and nitrotyrosine quantification. Further, the expression of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase was determined. NF-kappaB and myeloperoxidase levels were assessed in the hearts. Relative to N hearts, IH improved left ventricular function (Left ventricular developed pressure: N; 21.8 ± 3.4 vs. IH; 42.8 ± 7.1 mmHg; p < 0.05); reduced oxidative stress (Malondialdehyde: N; 14.4 ± 1.8 vs. IH; 7.3 ± 2.1 µmol/mg prot.; p < 0.05); and increased antioxidant enzymes expression. Supplementation with Ω3 induces similar responses as IH group. Our findings suggest that both, IH and Ω3 in an independent manner, induce functional improvement by antioxidant and anti-inflammatory mechanisms, establishing cardio-protection.


Asunto(s)
Mal de Altura/tratamiento farmacológico , Antioxidantes/farmacología , Cardiotónicos/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Hipoxia/tratamiento farmacológico , Adenosina Trifosfato/metabolismo , Mal de Altura/metabolismo , Animales , Suplementos Dietéticos , Metabolismo Energético/efectos de los fármacos , Corazón/efectos de los fármacos , Hipoxia/complicaciones , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Técnicas In Vitro , Inflamación/metabolismo , Inflamación/prevención & control , Masculino , Miocardio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Función Ventricular Izquierda/efectos de los fármacos
14.
J Physiol ; 592(3): 475-89, 2014 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-24247986

RESUMEN

Hypoxia is a common challenge to the fetus, promoting a physiological defence to redistribute blood flow towards the brain and away from peripheral circulations. During acute hypoxia, reactive oxygen species (ROS) interact with nitric oxide (NO) to provide an oxidant tone. This contributes to the mechanisms redistributing the fetal cardiac output, although the source of ROS is unknown. Here, we investigated whether ROS derived from xanthine oxidase (XO) contribute to the fetal peripheral vasoconstrictor response to hypoxia via interaction with NO-dependent mechanisms. Pregnant ewes and their fetuses were surgically prepared for long-term recording at 118 days of gestation (term approximately 145 days). After 5 days of recovery, mothers were infused i.v. for 30 min with either vehicle (n = 11), low dose (30 mg kg(-1), n = 5) or high dose (150 mg kg(-1), n = 9) allopurinol, or high dose allopurinol with fetal NO blockade (n = 6). Following allopurinol treatment, fetal hypoxia was induced by reducing maternal inspired O2 such that fetal basal P aO 2 decreased approximately by 50% for 30 min. Allopurinol inhibited the increase in fetal plasma uric acid and suppressed the fetal femoral vasoconstrictor, glycaemic and lactate acidaemic responses during hypoxia (all P < 0.05), effects that were restored to control levels with fetal NO blockade. The data provide evidence for the activation of fetal XO in vivo during hypoxia and for XO-derived ROS in contributing to the fetal peripheral vasoconstriction, part of the fetal defence to hypoxia. The data are of significance to the understanding of the physiological control of the fetal cardiovascular system during hypoxic stress. The findings are also of clinical relevance in the context of obstetric trials in which allopurinol is being administered to pregnant women when the fetus shows signs of hypoxic distress.


Asunto(s)
Presión Sanguínea , Corazón Fetal/fisiopatología , Hipoxia Fetal/fisiopatología , Frecuencia Cardíaca , Xantina Oxidasa/sangre , Alopurinol/farmacología , Animales , Glucemia/metabolismo , Inhibidores Enzimáticos/farmacología , Femenino , Hipoxia Fetal/sangre , Edad Gestacional , Ácido Láctico/sangre , Óxido Nítrico/sangre , Oxígeno/sangre , Consumo de Oxígeno , Embarazo , Especies Reactivas de Oxígeno/sangre , Flujo Sanguíneo Regional , Ovinos , Ácido Úrico/sangre , Vasoconstricción , Xantina Oxidasa/antagonistas & inhibidores
15.
Circ J ; 77(10): 2604-11, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23856654

RESUMEN

BACKGROUND: Fetal hypoxia is common and in vitro evidence supports its role in the programming of adult cardiovascular dysfunction through the generation of oxidative stress. Whether fetal chronic hypoxia programmes alterations in cardiovascular control in vivo, and if these alterations can be prevented by antioxidant treatment, is unknown. This study investigated the effects of prenatal fetal hypoxia, with and without maternal supplementation with vitamin C, on basal and stimulated cardiovascular function in vivo in the adult offspring at 4 months of age in the rat. METHODS AND RESULTS: From days 6 to 20 of pregnancy, Wistar rats were subjected to Normoxia, Hypoxia (13% O2), Hypoxia+Vitamin C (5mg/ml in drinking water) or Normoxia+Vitamin C. At 4 months, male offspring were instrumented under urethane anaesthesia. Basal mean arterial blood pressure, heart rate and heart rate variability (HRV) were assessed, and stimulated baroreflex curves were generated with phenylephrine and sodium nitroprusside. Chronic fetal hypoxia increased the LF/HF HRV ratio and baroreflex gain, effects prevented by vitamin C administration during pregnancy. CONCLUSIONS: Chronic intrauterine hypoxia programmes cardiovascular dysfunction in vivo in adult rat offspring; effects ameliorated by maternal treatment with vitamin C. The data support a role for fetal chronic hypoxia programming cardiovascular dysfunction in the adult rat offspring in vivo through the generation of oxidative stress in utero.


Asunto(s)
Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Enfermedades Cardiovasculares/prevención & control , Hipoxia Fetal/prevención & control , Animales , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Femenino , Hipoxia Fetal/fisiopatología , Hipoxia/complicaciones , Hipoxia/fisiopatología , Hipoxia/prevención & control , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas , Factores de Tiempo
16.
Am J Physiol Regul Integr Comp Physiol ; 304(4): R313-20, 2013 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-23255588

RESUMEN

Prenatal and early postnatal nutritional status may predispose offspring to impaired glucose tolerance and changes in insulin sensitivity in adult life. The long-term consequences of changes in maternal dietary fatty acid composition were determined in rats. From day 1 until day 12 of pregnancy, rats were given isocaloric diets containing 9% nonvitamin fat based on soybean, olive, fish (FO), linseed, or palm oil. Thereafter, they were maintained on the standard diet; offspring were studied at different ages. Body weight at 4, 8, and 12 mo and lumbar adipose tissue and liver weights at 12 mo did not differ between females on the different diets, whereas in males the corresponding values were all lower in the offspring from the FO group compared with the other dietary groups. Plasma glucose concentrations (both basal and after an oral glucose load) did not change with sex or dietary group, but plasma insulin concentrations were lower in females than in males and, in males, were lowest in the FO group. Similar relations were found with both the homeostasis model assessment of insulin resistance and insulin sensitivity index. In conclusion, the intake of more n-3 fatty acids (FO diet) during early pregnancy reduced both fat accretion and age-related decline in insulin sensitivity in male offspring but not in females. It is proposed that the lower adiposity caused by the increased n-3 fatty acids during the intrauterine life was responsible of the lower insulin resistance in male offspring.


Asunto(s)
Envejecimiento/efectos de los fármacos , Suplementos Dietéticos , Aceites de Pescado/administración & dosificación , Resistencia a la Insulina/fisiología , Fenómenos Fisiologicos de la Nutrición Prenatal , Tejido Adiposo/anatomía & histología , Tejido Adiposo/efectos de los fármacos , Envejecimiento/fisiología , Animales , Glucemia/efectos de los fármacos , Glucemia/fisiología , Peso Corporal/efectos de los fármacos , Ácidos Grasos Omega-3/administración & dosificación , Femenino , Homeostasis/efectos de los fármacos , Homeostasis/fisiología , Insulina/sangre , Masculino , Tamaño de los Órganos , Embarazo , Ratas , Factores Sexuales
17.
J Ethnopharmacol ; 143(3): 805-11, 2012 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-22921950

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The role of Azadirachta indica (neem) against Chagas disease and its antibiotic and antidiabetic action have been demonstrated in non-pregnant animals. However, the effects of neem on lipid metabolism and oxidative stress during pregnancy remain to be investigated. The objective of this study was to evaluate the effects of Azadirachta indica (neem) on maternal reproductive performance and biochemical parameters in non-diabetic and streptozotocin-induced mild diabetic rats (MD). MATERIALS AND METHODS: Pregnant rats were randomly distributed into six experimental groups: ND=non-treated non-diabetic (n=13); NDOil=non-diabetic treated with 1.2 mL/day neem seed oil (n=12); NDPA=non-diabetic treated with 1.0mg/mL/day azadirachtin (n=12); D=non-treated diabetic (n=13); DOil: diabetic treated with neem seed oil (n=12), and DPA=diabetic treated with azadirachtin, n=13. Treatment with either neem oil (1.2 mL/day) or azadirachtin (1.0mg/mL/day) was orally administered throughout pregnancy. Glucose test tolerance (GTT) was performed at day 17 of pregnancy and used as an inclusion criterion. At term pregnancy, maternal reproductive outcomes, lipid profile and oxidative stress status were assessed. RESULTS: Treatment with neem oil and azadirachtin during pregnancy (1) had no hypoglycemic and anti-hyperglycemic effects on non-diabetic and diabetic rats, respectively; (2) affected OGTT glycemic levels in diabetic rats; (3) increased the proportion of fetuses classified as small for pregnancy age (SPA) in all groups; and (4) did not interfere with the lipid profile in non-diabetic dams. Neem oil reduced the rate of total cholesterol and NEFA in diabetic animals. Both neem oil and azadirachtin increased lipoperoxidation, characterized by increased MDA levels in non-diabetic rats. CONCLUSION: Both neem seed oil and azadirachtin impaired intrauterine development and altered antioxidant/oxidative status during pregnancy.


Asunto(s)
Azadirachta , Desarrollo Fetal/efectos de los fármacos , Glicéridos/efectos adversos , Limoninas/efectos adversos , Terpenos/efectos adversos , Animales , Diabetes Mellitus Experimental/metabolismo , Femenino , Reabsorción del Feto , Prueba de Tolerancia a la Glucosa , Metabolismo de los Lípidos , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/metabolismo , Embarazo , Resultado del Embarazo , Embarazo en Diabéticas/metabolismo , Ratas , Semillas
18.
Prostaglandins Leukot Essent Fatty Acids ; 86(4-5): 167-74, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22444486

RESUMEN

Pregnant rats received soybean (SO), olive (OO), fish (FO) and linseed (LO) oil diets from conception to d12 of gestation (early diets) and standard diet thereafter. At d12 and d20 the lipoprotein lipase (LPL) activity was evaluated in maternal adipose tissues (ATs). Fatty Acid (FA) profile was determined in maternal lumbar AT (LAT), in milk and in pup's plasma and brain. LPL activity was higher in ATs at d12 than d20, all groups presenting hypertriglyceridemia at d20. At d12, the LO diet resulted higher LPL activity and incorporation of 18:3 n-3 into LAT. FA profile in maternal LAT at d20 and colostrum was similar to early diets, reflected also in FA composition of pup's plasma. In FO, brain phospholipids had higher 22:6 n-3 without affecting arachidonic acid. These results suggest that specifics dietary FA in early pregnancy modulates lipid metabolism and the provision of LC-PUFA in milk and pups brain.


Asunto(s)
Tejido Adiposo/metabolismo , Grasas de la Dieta/metabolismo , Ácidos Grasos/metabolismo , Preñez/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales/fisiología , Animales , Animales Recién Nacidos , Grasas Insaturadas en la Dieta/metabolismo , Grasas Insaturadas en la Dieta/farmacología , Femenino , Aceites de Pescado/farmacología , Embarazo , Ratas , Ratas Sprague-Dawley
19.
Lipids ; 45(5): 409-18, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20422462

RESUMEN

Dietary supplements of olive oil (OO) or fish oil (FO) during the first (G1: day 1-60) or second half of gestation (G2: day 60 to term, day 115) were offered to pregnant sows. The proportion of fatty acids in milk and plasma were determined by gas chromatography. When supplements were given during G1, the proportions of oleic acid (OA) and arachidonic acid (AA) in the plasma were higher in the OO group than in the FO group, whereas docosahexaenoic acid (DHA) was higher in the latter group at day 56 of gestation. These differences in plasma DHA were still apparent at day 7 of lactation. Similarly, DHA was also higher in the colostrum and milk on days 3 and 21 of lactation and in the plasma of piglets from FO dams compared to the OO group, whereas AA was lower. When the FO supplement was given during G2, AA was lower and DHA higher in the plasma at day 105 of gestation and at day 7 of lactation compared with the OO group. Likewise, DHA was greater in FO than in OO animals during lactation in colostrum and in milk on days 3 and 21 of lactation, and in 3-day old suckling piglets plasma, whereas AA was lower in these animals. Thus, maternal adipose tissue plays an important role in the storage of dietary long-chain polyunsaturated fatty acids (LCPUFA) during G1. They are mobilized around parturition for milk synthesis, and an excess of dietary n-3 LCPUFA decreases the availability of AA in suckling newborns.


Asunto(s)
Grasas de la Dieta/administración & dosificación , Lípidos/sangre , Leche/química , Preñez , Porcinos/fisiología , Animales , Animales Recién Nacidos , Femenino , Desarrollo Fetal , Lípidos/química , Embarazo , Porcinos/sangre
20.
Nutr Rev ; 67 Suppl 1: S140-4, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19453669

RESUMEN

Free radicals generated as byproducts of normal metabolism can damage biologically relevant molecules. When their generation is increased, damage can also be increased, resulting in the development of many pathological conditions. Antioxidant defenses protect the body from the detrimental effects of free radicals. Dietary fruits and vegetables provide a reasonable amount of compounds that act as physiological antioxidants. Although existing knowledge does not allow a final and conclusive assessment of the relevance of antioxidants for health, it does provide the basis for its rational consideration. This paper addresses the specific aspects of antioxidant supplementation in health and disease.


Asunto(s)
Envejecimiento/fisiología , Antioxidantes/administración & dosificación , Enfermedad Crónica/prevención & control , Neoplasias/prevención & control , Estrés Oxidativo/efectos de los fármacos , Envejecimiento/efectos de los fármacos , Antioxidantes/farmacología , Suplementos Dietéticos , Medicina Basada en la Evidencia , Ejercicio Físico/fisiología , Análisis de los Alimentos , Humanos , Valor Nutritivo , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/efectos adversos , Especies Reactivas de Oxígeno/metabolismo
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