Publications by authors named "Maria-Luisa Ojeda"

14 Publications

  • Page 1 of 1

Selenoproteins and renal programming in metabolic syndrome-exposed rat offspring.

Food Funct 2020 May 28;11(5):3904-3915. Epub 2020 Apr 28.

Department of Physiology, Faculty of Pharmacy, Seville University, 41012 Seville, Spain.

Maternal metabolic syndrome (MS) during gestation and lactation leads to several cardiometabolic changes related to selenium (Se) status and selenoprotein expression in offspring. However, little is known about kidney programming and antioxidant selenoprotein status in MS pups. To gain more knowledge on this subject, two experimental groups of dam rats were used: Control (Se: 0.1 ppm) and MS (fructose 65% and Se: 0.1 ppm). At the end of lactation, Se deposits in kidneys, selenoprotein expression (GPx1, GPx3, GPx4 and selenoprotein P), oxidative balance and AMP-activated protein kinase (AMPK) and activated transcriptional factor NF-κB expression were measured. Kidney functional parameters, albuminuria, creatinine clearance, aldosteronemia, and water and electrolyte balance, were also evaluated. One week later systolic blood pressure was measured. Lipid peroxidation takes place in the kidneys of MS pups and Se, selenoproteins and NF-κB expression increased, while AMPK activation decreased. MS pups have albuminuria and low creatinine clearance which implies glomerular renal impairment with protein loss. They also present hypernatremia and hyperaldosteronemia, together with a high renal Na reabsorption, leading to a hypertensive status, which was detected in these animals one week later. Since these alterations seem to be related, at least in part, to oxidative stress, the increase in Se and selenoproteins found in the kidneys of these pups seems to be beneficial, avoiding a higher lipid oxidation. However, in order to analyze the possible global beneficial role of Se in kidneys during MS exposure, more data are necessary to document the relationships between GPx4 and NF-κB, and SelP and AMPK in kidneys.
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http://dx.doi.org/10.1039/d0fo00264jDOI Listing
May 2020

High- and low- selenium diets affect endocrine energy balance during early programming.

Toxicol Appl Pharmacol 2019 11 5;382:114744. Epub 2019 Sep 5.

Department of Physiology, Faculty of Pharmacy, Seville University, 41012 Seville, Spain.

High- and low- Se diets received by dams during gestation and lactation are related to insulin resistance in their pups. High-Se diet leads to an increase in serum insulin levels, which does not function properly, and an anabolic process. Low-Se diet is related to very low insulin values and an extreme catabolic energy imbalance. Selenoproteins have been implicated directly in the general endocrine regulation of appetite and energy homeostasis. To obtain information concerning how Se intake by dams is involved in regulating endocrine energy balance in progeny, three experimental groups of dam rats were used: control (Se: 0.1 ppm), Se-supplemented (Se: 0.5 ppm) and Se-deficient (Se: 0.01 ppm). At the end of lactation (21d old), the pups' appetite profile, Se levels, peptides from gastrointestinal tract (including pancreas), leptin, thyroid hormones, skeletal growth markers and cytokines in serum were measured. Low-Se diet leads to severe growth retardation, underdeveloped glands, a non-functional pancreas, non-operative high serum leptin levels and low GIT-anorexigenic signals. High-Se diet leads to non-operative high insulin secretion, obesity, inflammation and low leptin levels. These results point to Se as an important marker and a possible dietary supplementation treatment for gestating and lactating mothers in order to avoid metabolic disorders such as gestational diabetes or intrauterine growth retardation which could affect their progeny's future health in adulthood.
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http://dx.doi.org/10.1016/j.taap.2019.114744DOI Listing
November 2019

Maternal metabolic syndrome and selenium: Endocrine energy balance during early programming.

Life Sci 2019 Sep 23;233:116689. Epub 2019 Jul 23.

Department of Physiology, Faculty of Pharmacy, Seville University, 41012 Seville, Spain.

Background: Maternal metabolic syndrome during gestation and lactation leads to several Se-status-related metabolic changes in offspring. MS leads to hepatomegaly, liver oxidation, resistance to insulin challenges and selenoptroteins expression upregulation, producing an energy imbalance in hepatocytes. As Se is necessary for correct heart function, Se deposits are depleted and selenoproteins expression downregulated in heart; this depletion being related to cardiovascular damage. Recently, selenoproteins have been directly implicated in the central endocrine regulation of appetite and energy homeostasis.

Methods: To obtain information about how Se is involved in regulating endocrine peripheral energy balance during MS process, two experimental groups of dam rats were used: control (Se: 0.1 ppm) and MS (Fructose 65% and Se: 0.1 ppm). At the end of lactation (21d old), the pups' appetite profile, tissular Se deposits and peptides from gastrointestinal tract (including pancreas), leptin, skeletal growth markers and cytokines in serum were measured.

Results: MS-exposed pups present changes in Se homeostasis, appetite profile and endocrine energy balance signals related to impaired insulin secretion and high leptin serum values. This profoundly affects the pups' growth profile since muscle and bones are in catabolic process and brown adipose tissue (BAT) mass decreases.

Conclusion: These results indicate that the pups are suffering a process similar to diabetes type 1 which appeared when dams received low Se dietary supply and they point to Se as an important marker and key treatment for these disorders during gestation and lactation that affect future adult health.
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http://dx.doi.org/10.1016/j.lfs.2019.116689DOI Listing
September 2019

Binge drinking affects kidney function, osmotic balance, aldosterone levels, and arterial pressure in adolescent rats: the potential hypotensive effect of selenium mediated by improvements in oxidative balance.

Hypertens Res 2019 10 9;42(10):1495-1506. Epub 2019 May 9.

Department of Physiology, Faculty of Pharmacy, Seville University, 41012, Seville, Spain.

Binge drinking (BD) during adolescence is related to hypertension. There are, however, few studies concerning the effects of BD on kidney function and osmotic balance in relation to arterial pressure. The mechanism by which BD affects kidney function is related to oxidation and inflammation. Recently, Se, an essential trace element possessing antioxidant properties, has also been shown to be related to renal Na/K-ATPase activity. This study examined the protective effects of 0.4 ppm selenite administered to adolescent rats in an intermittent i.p. BD model. BD consumption depleted kidney and serum Se deposits, decreased GPx activity, and increased biomolecule oxidation in these locations. In the kidneys, GPx1, GPx3, GPx4, and NF-κB expression also decreased, coinciding with an increase in caspase-3 expression. BD decreased creatinine clearance and fractional Na excretion (EFNa), increased transtubular K excretion (TTKG) and serum aldosterone (Aldo) levels, and reduced relative Aldo clearance. These effects led to hypernatremia, low urinary flow, and high systolic blood pressure. Se supplementation to BD rats significantly improved oxidative balance, and kidney GPx, NF-κB, and caspase-3 expression; slightly increased EFNa and slightly decreased TTKG and serum Aldo levels; and greatly increased relative Aldo clearance. Se supplementation did not, however, modify creatinine clearance. In conclusion, BD triggers kidney osmotic and ionic imbalances, which contribute to increasing systolic blood pressure. These disturbances could be related in part to Se and selenoprotein GPxs, which decrease oxidative, inflammatory and apoptotic alterations in the kidneys. Se supplementation prevents these changes, improves ionic disturbances, and decreases serum Aldo levels and systolic blood pressure.
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http://dx.doi.org/10.1038/s41440-019-0265-zDOI Listing
October 2019

Maternal selenium status is profoundly involved in metabolic fetal programming by modulating insulin resistance, oxidative balance and energy homeostasis.

Eur J Nutr 2019 Dec 1;58(8):3171-3181. Epub 2018 Dec 1.

Department of Physiology, Faculty of Pharmacy, Seville University, C/Professor García González, nº 2, 41012, Seville, Spain.

Purpose: High and low levels of selenium (Se) have been related to metabolic disorders in dams and in their offspring. Their relationship to oxidative balance and to AMP-activated protein kinase (AMPK) is some of the mechanisms proposed. The aim of this study is to acquire information about how Se is involved in metabolic programming.

Methods: Three experimental groups of dam rats were used: control (Se: 0.1 ppm), Se supplemented (Se: 0.5 ppm) and Se deficient (Se: 0.01 ppm). At the end of lactation, the pups' metabolic profile, oxidative balance, Se levels, selenoproteins and IRS-1 hepatic expression, as well as hepatic AMPK activation were measured.

Results: The experimental groups present deep changes in Se homeostasis, selenoproteins and IRS-1 hepatic expression, oxidative balance, AMPK activation ratio and insulin levels. They do, however, have different metabolic profiles.

Conclusions: High- and low-Se diets are linked to insulin resistance, yet the mechanisms involved are completely opposite.
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http://dx.doi.org/10.1007/s00394-018-1861-4DOI Listing
December 2019

Heart selenoproteins status of metabolic syndrome-exposed pups: A potential target for attenuating cardiac damage.

Mol Nutr Food Res 2016 12 10;60(12):2633-2641. Epub 2016 Oct 10.

Department of Physiology, Faculty of Pharmacy, Seville University, Seville, Spain.

Scope: Cardiac hypertrophy is the greatest complication in metabolic syndrome (MS), in dams and in offspring. The most effective therapies to avoid the evolution of MS are anti-oxidants, anti-inflammatories, and insulin sensitizers. Among anti-oxidant elements, Selenium (Se) exerts its functions through selenoproteins, which are essential for the correct functioning of the cardiovascular system. The aim of the study is analyze selenoproteins' implication in the transmission of future cardiovascular problems to MS progeny.

Methods And Results: Heart Se deposits, antioxidant enzymes' activities, biomolecular oxidation, and the expression of selenoproteins, AMPK, and NF-kB were measured in the offspring of dams exposed to a fructose-rich diet (65%) during gestation and lactation, with a normal Se content (0.1 ppm). Thyroid hormones and MCP-1 serum levels, as well as blood pressure and heart rate were also measured. Fructose-exposed pups have cardiomegaly, oxidation, and depletion in Se heart deposits, a decrease in selenoproteins' expression and in the p-AMPK/AMPKt energy ratio; an increase in NF-kB p65 expression, and a decrease of thyroid hormones and MCP-1. Heart rate and blood pressure were altered.

Conclusion: These data indicate that dietary Se supplementation could be an inexpensive therapy for avoiding future cardiovascular complication in the progeny of MS dams.
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http://dx.doi.org/10.1002/mnfr.201600511DOI Listing
December 2016

Binge drinking during adolescence disrupts Se homeostasis and its main hepatic selenoprotein expression.

Alcohol Clin Exp Res 2015 May 10;39(5):818-26. Epub 2015 Apr 10.

Department of Physiology, Faculty of Pharmacy, Seville University, Seville, Spain.

Background: Binge drinking (BD) is the most common ethanol (EtOH) intake consumption model among teenagers, but little is known about its effects on the liver. During its hepatic metabolism, acute alcohol exposure produces a great amount of reactive oxygen species which contributes to alcohol-induced liver injury. Selenium (Se) plays a key role in antioxidant defense as it forms part of selenoproteins, such as the antioxidant glutathione peroxidases (GPxs) or the selenoprotein P (SelP), synthesized mainly in liver. Chronic EtOH consumption decreases both Se deposits and this tissue's antioxidant activity.

Methods: Two BD administration routes (oral and intraperitoneal) were used in adolescent rats to analyze Se homeostasis; the main hepatic selenoproteins' expression: GPx1, GPx4, and SelP, and their biological roles related to oxidation. Their relationship with inflammatory processes was also determined by analyzing the expression of the transcriptional factor nuclear factor-kappa beta (NF-κB).

Results: It has been demonstrated for the first time that BD in adolescents alters Se homeostasis regardless of the administration route employed, despite the fact that the BD oral group ingested less Se in diet. This decrease of Se in serum and liver is directly related to a decrease in serum GPx3 and hepatic GPx1 activity, contributing to the oxidative imbalance found. The depletion of Se detected in liver affects GPx1 expression and, surprisingly, GPx4 expression. This could be related to the lower expression of the transcriptional factor NF-κB in the liver, a key player in the regulation of inflammatory processes.

Conclusions: Due to the above, and to find whether a Se supplementation therapy improves these situations, it would be interesting to explore in more depth the relationship between Se, the high oxidation found, and the depressed immune response reported in BD adolescents.
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http://dx.doi.org/10.1111/acer.12707DOI Listing
May 2015

Oral or intraperitoneal binge drinking and oxidative balance in adolescent rats.

Chem Res Toxicol 2014 Nov 5;27(11):1926-33. Epub 2014 Nov 5.

Department of Physiology, Faculty of Pharmacy, Seville University , 41012 Seville, Spain.

Oxidative imbalance is one of the most important mechanisms of alcohol-induced injury. Acute alcohol exposure induces a significant amount of reactive oxygen species during its hepatic metabolism via the microsomal ethanol oxidizing system. During adolescence, the physiological development is still taking place; therefore, ethanol's effects differ in adolescents compared to that in adults. Because binge drinking is the most important model of ethanol intake used by adolescents and because little is known about its effects on the liver, we have used two routes of acute ethanol administration (oral and intraperitoneal) in adolescent rats in order to analyze the oxidative damage caused in the periphery and liver. Here, it has been demonstrated for the first time that binge drinking in adolescents causes peripheral oxidation of lipid and DNA as well as lipid and protein hepatic oxidation, which are related to lower glutathione peroxidise (GPx) activity, higher catalase (CAT) activity, and higher expression of NADPHoxidase, contributing to hepatic damage. In addition, it is shown that the intraperitoneal administration route results in increased oxidative damage, which is probably related to the resulting general stress response that causes higher DNA and protein oxidation due to higher NADPHoxidase expression and higher CAT and superoxide dismutase (SOD) activities. According to these results, it is concluded that binge drinking induces hepatic damage during adolescence, at least in part, as consequence of oxidative stress because the antioxidant response was insufficient to avoid liver oxidation. Alcohol administered intraperitoneally provoked more DNA oxidation than that from the oral alcohol exposure model.
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http://dx.doi.org/10.1021/tx5002628DOI Listing
November 2014

Selenium or selenium plus folic acid-supplemented diets ameliorate renal oxidation in ethanol-exposed pups.

Alcohol Clin Exp Res 2012 Nov 6;36(11):1863-72. Epub 2012 Apr 6.

Department of Physiology and Zoology, Faculty of Pharmacy, Seville University, Seville, Spain.

Background: Ethanol (EtOH) exposure during gestation and lactation induces an oxidative stress in offspring. In kidney, the oxidative damage is the primary pathway to alcohol-induced injury. In this study, we have demonstrated that a diet supplemented with selenium (Se) (0.5 ppm) or with Se (0.5 ppm) + folic acid (8 ppm) administered to EtOH-exposed (20% v/v) dams during gestation and lactation prevents the oxidative EtOH-provoked effects in their offspring's kidneys.

Methods: All the studies were performed on 21-day-old pups. Serum, urine, and kidney Se levels were assessed by graphite-furnace atomic absorption spectrometry. Se and creatinine clearance, antioxidant enzyme activities, and lipid and protein peroxidation were determined by a spectrophotometric method in kidney.

Results: Dietary supplementation treatments used could not improve the glomerular filtration function altered by EtOH exposure during gestation and lactation; however, they did improve renal Se deposits, renal development, and renal protein content while decreasing lipid and protein oxidation and modifying antioxidant enzymes' activity.

Conclusions: Se or Se + folic acid supplementations improve renal development and protein content and modify antioxidant enzymes' activity, decreasing lipid and protein oxidation after EtOH exposure. In this context, a double-supplemented diet appears to reduce protein peroxidation more efficiently than the Se-only-supplemented one, probably via superoxide dismutase and catalase.
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http://dx.doi.org/10.1111/j.1530-0277.2012.01788.xDOI Listing
November 2012

Se bioavailability and glutathione peroxidase activity in iron deficient rats.

J Trace Elem Med Biol 2011 Jan 28;25(1):42-6. Epub 2011 Jan 28.

Department of Physiology and Institute of Nutrition and Food Technology, University of Granada, E-18071 Granada, Spain.

Little information is available on the relationship of Se deposit in target organs and GPx activity in iron deficiency anemia. As red blood cells (RBCs) play a crucial role on Se metabolism and during Fe deficiency anemia a lower count of RBCs is featured, we aimed to investigate the influence of this pathology on Se bioavailability and the relationship with antioxidant status. 20 male Wistar rats were randomly divided into two groups, a control group receiving AIN-93G diet with normal Fe content (45mg/kg diet) and the Fe-deficient group receiving AIN-93G diet with low Fe content (5mg/kg diet) for 40 days. Both diets were prepared with an adequate Se content (0.180mg/kg diet). The digestive and metabolic utilization of Se, the distribution in target organ, the GPx activity and TBARS production were measured after receiving the diets. Se retention increased (P<0.001) in the anemic group, fact that contributes to keep the enzymatic antioxidant activity of GPx in normal levels and the tendency observed is that stored Se increased in the organs, especially in kidney (P<0.01), however, a lower Se deposit was found in sternum of anemic rats (P<0.001). The lower count of RBCs featured in this pathology (P<0.001) causes a decrease of Se concentration in sternum meanwhile the increase in kidney deposit is a consequence of the lower urinary losses (P<0.001).
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http://dx.doi.org/10.1016/j.jtemb.2010.12.005DOI Listing
January 2011

Ethanol consumption by Wistar rat dams affects selenium bioavailability and antioxidant balance in their progeny.

Int J Environ Res Public Health 2009 08 30;6(8):2139-49. Epub 2009 Jul 30.

Department of Physiology and Zoology, Faculty of Pharmacy, Seville University, Seville, Spain.

Ethanol consumption affects maternal nutrition, the mothers' antioxidant balance and the future health of their progeny. Selenium (Se) is a trace element cofactor of the enzyme glutathione peroxidase (GPx). We will study the effect of ethanol on Se bioavailability in dams and in their progeny. We have used three experimental groups of dams: control, chronic ethanol and pair-fed; and three groups of pups. Se levels were measured by graphite-furnace atomic absorption spectrometry. Serum and hepatic GPx activity was determined by spectrometry. We have concluded that ethanol decreased Se retention in dams, affecting their tissue Se deposits and those of their offspring, while also compromising their progeny's weight and oxidation balance. These effects of ethanol are caused by a reduction in Se intake and a direct alcohol-generated oxidation action.
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http://dx.doi.org/10.3390/ijerph6082139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738878PMC
August 2009

Beneficial role of dietary folic acid on cholesterol and bile acid metabolism in ethanol-fed rats.

J Stud Alcohol Drugs 2009 Jul;70(4):615-22

Departamento de Fisiología y Zoología, Universidad de Sevilla, C/Tramontana s/n, Sevilla 41012, Spain.

Objective: Cholesterol metabolism is altered by chronic ethanol consumption. In previous articles, we demonstrated the anti-oxidant capacity of folic acid, which may be useful in the prevention of damage provoked by ethanol. We want to determine the effects of ethanol on cholesterol and bile metabolism and whether a folic acid-supplemented diet could change alterations provoked by a chronic ethanol intake in rats.

Method: We used four experimental groups: (1) control, (2) alcohol, (3) alcohol supplemented with folic acid, and (4) control supplemented with folic acid. In all the experimental groups, we measured hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and cholesterol and bile acids in serum, liver, bile, and feces.

Results: We have found that the alcohol-fed groups showed high hepatic HMG-CoA reductase activity, total hepatic and serum cholesterol concentration, bile cholesterol secretion concentration, and cholesterol enterohepatic circulation. Total serum and hepatic cholesterol levels decreased when alcohol-fed rats were supplemented with folic acid. The hepatic bile acid concentration increased in both chronic ethanol groups. Folic acid supplementation significantly increased bile cholesterol secretion, the bile acids in bile, and fecal bile acid excretion in ethanol-exposed rats. The independent bile acid fraction showed no significant differences between both ethanol groups with respect to Na+, K+, and Cl- concentrations.

Conclusions: Folic acid increases bile flow, bile acid synthesis from cholesterol, and bile acid excretion via feces, thus provoking a decrease in serum and hepatic cholesterol. However none of these actions were observed in supplemented control rats. This, therefore, could be yet another beneficial effect of folic acid on alcoholic patients.
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http://dx.doi.org/10.15288/jsad.2009.70.615DOI Listing
July 2009

Mutation study of Spanish patients with hereditary hemorrhagic telangiectasia.

BMC Med Genet 2008 Aug 1;9:75. Epub 2008 Aug 1.

Centro de Investigaciones Biologicas, CSIC, Ramiro de Maeztu, 9, Madrid 28040, Spain.

Background: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant and age-dependent vascular disorder characterised mainly by mutations in the Endoglin (ENG) or activin receptor-like kinase-1 (ALK1, ACVRL1) genes.

Methods: Here, we have identified 22 ALK1 mutations and 15 ENG mutations, many of which had not previously been reported, in independent Spanish families afflicted with HHT.

Results: We identified mutations in thirty-seven unrelated families. A detailed analysis of clinical symptoms was recorded for each patient analyzed, with a higher significant presence of pulmonary arteriovenous malformations (PAVM) in HHT1 patients over HHT2. Twenty-two mutations in ALK1 and fifteen in ENG genes were identified. Many of them, almost half, represented new mutations in ALK1 and in ENG. Missense mutations in ENG and ALK1 were localized in a tridimensional protein structure model.

Conclusion: Overall, ALK1 mutations (HHT2) were predominant over ENG mutations (HHT1) in our Spanish population, in agreement with previous data from our country and other Mediterranean countries (France, Italy), but different to Northern Europe or North America. There was a significant increase of PAVM associated with HHT1 over HHT2 in these families.
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http://dx.doi.org/10.1186/1471-2350-9-75DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518546PMC
August 2008

Surfactantless synthesis and textural properties of self-assembled mesoporous SnO(2).

Nanotechnology 2006 Jul 15;17(14):3347-58. Epub 2006 Jun 15.

Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, PO Box 55-534, México, DF 09340, Mexico.

Ordered surfactantless self-assembled, mesoporous SnO(2) adsorbents, consisting of tubular voids of nanometric sizes, are prepared by the sol-gel processing of tin (IV) tetra-tert-amyloxide, Sn(OAm(t))(4), whose molecules have been previously chelated with acetylacetone in the absence of water, to modulate their reactivity and to promote an incipient self-assembling of -O-Sn-O oligomeric species; ultimately, the necessary amount of water to induce the hydrolysis-condensation reactions is added to this aged sol, then producing tubular pore templates within the SnO(2) xerogel network. A collection of mesoporous SnO(2) xerogels of assorted structural properties has been obtained after calcination in air of precursory gels proceeding from an aged mixture of Sn(OAm(t))(4) and acetylacetone at temperatures in the range 200-1000 degrees C. N(2) sorption isotherms measured on these SnO(2) solids evidence mesoporous structures of diverse textural characteristics (i.e. pore widths of 3-50 nm and surface areas of 10-140 m(2) g(-1)) in which voids virtually behave as if they are independent cylindrical pores during capillary condensation and evaporation.
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http://dx.doi.org/10.1088/0957-4484/17/14/003DOI Listing
July 2006