Maria Rivoira - Academia.edu (original) (raw)

Papers by Maria Rivoira

World Journal of Gastroenterology, 2018

Glutathione (GSH) is a tripeptide that constitutes one of the main intracellular reducing compoun... more Glutathione (GSH) is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca 2+ absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K3, sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca 2+ absorption. The GSH depleting drugs switch the redox state towards an oxidant condition provoking oxidative/nitrosative stress and inflammation, which lead to apoptosis and/or autophagy of the enterocytes. Either the transcellular Ca 2+ transport or the paracellular Ca 2+ route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca 2+ pathway are decreased. The flavonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca 2+ absorption, not only by restoration of the GSH levels in the intestine but also by their anti-apoptotic properties. Ursodeoxycholic acid, melatonin and glutamine also block the inhibition of Ca 2+ transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca 2+ absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety, pharmacokinetics and pharmacodynamics of them.

Archives of Biochemistry and Biophysics, 2017

This study tries to elucidate the mechanisms by which fructose rich diets (FRD) inhibit the rat i... more This study tries to elucidate the mechanisms by which fructose rich diets (FRD) inhibit the rat intestinal Ca 2+ absorption, and determine if any or all underlying alterations are prevented by naringin (NAR). Male rats were divided into: 1) controls, 2) treated with FRD, 3) treated with FRD and NAR. The intestinal Ca 2+ absorption and proteins of the transcellular and paracellular Ca 2+ pathways were measured. Oxidative/nitrosative stress and inflammation parameters were evaluated. FRD rats showed inhibition of the intestinal Ca 2+ absorption and decrease in the protein expression of molecules of both Ca 2+ pathways, which were blocked by NAR. FRD rats showed an increase in the superoxide anion, a decrease in the glutathione and in the enzymatic activities of the antioxidant system, as well as an increase in the NO content and in the nitrotyrosine content of proteins. They also exhibited an increase in both IL-6 and nuclear NF-κB. All these changes were prevented by NAR. In conclusion, FRD inhibit both pathways of the intestinal Ca 2+ absorption due to the oxidative/nitrosative stress and inflammation. Since NAR prevents the oxidative/nitrosative stress and inflammation, it might be a drug to avoid alteration in the intestinal Ca 2+ absorption caused by FRD.

Archives of Biochemistry and Biophysics, 2018

The aim of this work was to know whether naringin (NA) could prevent the bone complications in a ... more The aim of this work was to know whether naringin (NA) could prevent the bone complications in a model of streptozotocin (STZ) induced diabetes. Rats were divided in: 1) controls, 2) STZ-rats, 3) STZ-rats treated with 40 mg NA/kg, and 4) STZ-rats treated with 80 mg NA/kg. BMD and BMC were performed by DEXA. Bone histomorphometry and histology as well as TRAP staining were done in tibia. Osteocalcin (OCN) was determined in bone and serum. Glutathione content and SOD and catalase activities were assayed in bone marrow from femur. The data showed that NA80 increased the BMD and BMC from the long bones of STZ-rats. Both NA40 and NA80 normalized the trabecular number and the trabecular separations. An increase in the number of adipocytes and TRAP(+) cells in tibia from STZ-rats was blocked by NA. NA40 treatment increased the number of OCN(+) cells, but only the NA80 treatment allowed to reach the control values. NA normalized the SOD and catalase activities in bone marrow of femur from STZ-rats. In conclusion, NA avoids alterations in the physical properties and microstructure of bone from STZ-rats probably by stimulation of osteoblastogenesis, inhibition of the osteoclastogenesis and adipogenesis via blocking the oxidative stress.

Current medicinal chemistry, Nov 16, 2017

Bile acids (BAs) are synthesized in the liver and are among the main components of bile. For many... more Bile acids (BAs) are synthesized in the liver and are among the main components of bile. For many years, it was thought that they have only a role as emulsifiers of fat in the small intestine facilitating the absorption of lipids and lipid soluble vitamins. Lately, they are also considered important signaling molecules, not only by regulating their own synthesis, but also having a role in several metabolic diseases. In this review we focus on the effect of deoxycholic, ursodeoxycholic and litocholic acids and their combination upon the intestinal Ca2+ absorption. To make the actions of those BAs clear on this physiological process, an overview of current information about the mechanisms by which the intestinal Ca2+ occurs is described. Finally, detailed statements related to the modulation of redox state, apoptosis and autophagy as molecular mechanisms involved in the action of BAs on intestinal Ca2+ absorption are discussed. Although the mechanisms are still not completely understo...

Biochemistry and cell biology = Biochimie et biologie cellulaire, Apr 1, 2017

LCA and 1,25(OH)2D3 are vitamin D receptor ligands with different binding affinity. The secostero... more LCA and 1,25(OH)2D3 are vitamin D receptor ligands with different binding affinity. The secosteroid stimulates intestinal Ca(2+) absorption. Whether LCA alters this process remains unknown. The aim of our work was to determine the effect of LCA on intestinal Ca(2+) absorption in the absence or presence of NaDOC, bile acid that inhibits the cation transport. The data show that LCA by itself did not alter intestinal Ca(2+) absorption, but prevented the inhibitory effect of NaDOC. The concomitant administration of LCA avoided the reduction of intestinal alkaline phosphatase activity caused by NaDOC. In addition, LCA blocked a decrease caused by NaDOC on gene and protein expression of molecules involved in the transcellular pathway of intestinal Ca(2+) absorption. The oxidative stress and apoptosis triggered by NaDOC were abrogated by LCA co-treatment. In conclusion, LCA placed in the intestinal lumen protects intestinal Ca(2+) absorption against the inhibitory effects caused by NaDOC. ...

Archives of Biochemistry and Biophysics, 2016

The aim of this work was to study the effect of sodium deoxycholate (NaDOC) and ursodeoxycholic a... more The aim of this work was to study the effect of sodium deoxycholate (NaDOC) and ursodeoxycholic acid (UDCA) on Ca(2+) uptake by enterocytes and the underlying mechanisms. Rats were divided into four groups: a) controls, b) treated with NaDOC, c) treated with UDCA d) treated with NaDOC and UDCA. Ca(2+) uptake was studied in enterocytes with different degrees of maturation. Apoptosis, autophagy and NO content and iNOS protein expression were evaluated. NaDOC decreased and UDCA increased Ca(2+) uptake only in mature enterocytes. The enhancement of protein expression of Fas, FasL, caspase-8 and caspase-3 activity by NaDOC indicates triggering of the apoptotic extrinsic pathway, which was blocked by UDCA. NO content and iNOS protein expression were enhanced by NaDOC, and avoided by UDCA. The increment of acidic vesicular organelles and LC3 II produced by NaDOC was also prevented by UDCA. In conclusion, the inhibitory effects of NaDOC on intestinal Ca(2+) absorption occur by decreasing the Ca(2+) uptake by mature enterocytes. NaDOC triggers apoptosis and autophagy, in part as a result of nitrosative stress. In contrast, UDCA increases the Ca(2+) uptake by mature enterocytes, and in combination with NaDOC acts as an antiapoptotic and antiautophagic agent normalizing the transcellular Ca(2+) pathway.

Nutrition Research Reviews, 2015

The intestine is the only gate for the entry of Ca to the body in humans and mammals. The entranc... more The intestine is the only gate for the entry of Ca to the body in humans and mammals. The entrance of Ca occurs via paracellular and intracellular pathways. All steps of the latter pathway are regulated by calcitriol and by other hormones. Dietary and pharmacological compounds also modulate the intestinal Ca absorption process. Among them, dietary Ca and P are known to alter the lipid and protein composition of the brush-border and basolateral membranes and, consequently, Ca transport. Ca intakes are below the requirements recommended by health professionals in most countries, triggering important health problems. Chronic low Ca intake has been related to illness conditions such as osteoporosis, hypertension, renal lithiasis and incidences of human cancer. Carbohydrates, mainly lactose, and prebiotics have been described as positive modulators of intestinal Ca absorption. Apparently, high meat proteins increase intestinal Ca absorption while the effect of dietary lipids remains uncl...

Biochimica et biophysica acta, 2015

The aim was to determine the intestinal Ca(2+) absorption in type I diabetic rats after different... more The aim was to determine the intestinal Ca(2+) absorption in type I diabetic rats after different times of STZ induction, as well as the gene and protein expression of molecules involved in both the transcellular and paracellular Ca(2+) pathways. The redox state and the antioxidant enzymes of the enterocytes were also evaluated in duodenum from either diabetic or insulin-treated diabetic rats as compared to control rats. Male Wistar rats (150-200g) were divided into two groups: 1) controls and 2) STZ-induced diabetic rats (60mg/kg b.w.). A group of diabetic rats received insulin for five days. The insulin was adjusted daily to maintain a normal blood glucose level. Five 5 d after STZ injection, there was a reduction in the intestinal Ca(2+) absorption, which was maintained for 30 d and disappeared at 60 d. Similar changes occurred in the GSH and (˙)O2(-) levels. The protein expression of molecules involved in the transcellular pathway increased at 5 and 30 d returning to control val...

Melatonin and Melatonergic Drugs in Clinical Practice, 2013

Melatonin (MEL) is a pleiotropic hormone which exerts its action through different mechanisms, ei... more Melatonin (MEL) is a pleiotropic hormone which exerts its action through different mechanisms, either by binding to its receptors or by acting as an antioxidant molecule and ROS scavenger. Its mechanisms of action together with the wide distribution of MT1 and MT2 receptors have provoked an ever-increasing number of clinical trials in the last two decades. These studies have evaluated the exogenous administration of MEL in different doses and formulations to prevent or to treat many health disorders. The predominant field of research has been the treatment of insomnia and other circadian rhythm disorders due to the confirmed resynchronizing properties of this indolamine. However, in the last decade, a profound interest has arisen concerning its potential therapeutic value in different conditions such as cancer, cardiovascular diseases, gastrointestinal problems, and inflammatory states, among others. The relatively low toxicity of MEL over a wide range of doses has made the research even more promising. However, new multicenter clinical trials could shed light on different aspects of MEL’s clinical uses contributing thus to clarify the conditions in which MEL might be considered as a first-line therapeutical strategy and to identify when the combination of MEL with other drugs is necessary. In this chapter, we revise the milestones in the field of MEL research from its discovery to the present time and analyze the future perspectives of its clinical uses.

Journal of Bone and Mineral Metabolism, 2008

The aim of this study was to determine genotypes and clinical aspects associated with bone minera... more The aim of this study was to determine genotypes and clinical aspects associated with bone mineral density (BMD) in postmenopausal women from Córdoba, Argentina. Polymorphisms were assessed by RFLP-PCR technique using BsmI and FokI for vitamin D receptor gene (VDR) and XbaI and PvuII for estrogen receptor-alpha gene (ERalpha) as restrictases. Sixty-eight healthy, 54 osteopenic, and 64 osteoporotic postmenopausal women were recruited. Femoral neck and lumbar spine BMD were inversely correlated with age in the entire analyzed population. Height was lower in osteopenic and osteoporotic women as compared to healthy women (P < 0.05). Weight and body mass index (BMI) were the lowest in osteoporotic women (P < 0.01 versus healthy group). Serum procollagen type I Nterminal propeptide (PINP) was higher in osteoporotic women as compared to the other groups. Distribution of VDR and ERalpha genotypes was similar in the three groups. Genotype bb (VDR) was associated with low values of lumbar BMD in the healthy group (P < 0.05 versus genotype Bb), and with low values of femoral BMD (P…

Digestion, 2008

An overview of current information on the mechanisms by which intestinal calcium absorption occur... more An overview of current information on the mechanisms by which intestinal calcium absorption occurs is described in this article. Both paracellular and transcellular pathways are analyzed. Special emphasis focuses on molecules participating in the latter pathway, such as TRPV5 and TRPV6 channels, located in the apical region of the enterocytes, CB9k and CB28k, presumably involved in the cation movement from the apical to the basolateral pole of the cell, and PMCA1b and Na+/Ca2+ exchanger, proteins that extrude Ca2+ from the cells. Current concepts on the relative importance of paracellular and transcellular calcium transport and the vitamin D dependence of each pathway are referred and analyzed showing the contrasting views on this issue. More detailed information is given regarding the stimulatory effect of vitamin D on intestinal Ca2+ absorption either in animal models or in the human intestine. The possible mechanisms triggered by hormones such as PTH, calcitonin, estrogen, thyroi...

Bone, 2011

Diabetes mellitus (DM) type I is a disorder characterized by hyperglycemia due to a deficient ins... more Diabetes mellitus (DM) type I is a disorder characterized by hyperglycemia due to a deficient insulin secretion. Alterations in different organs have been observed in DM. The aim of this work was to study intestinal calcium absorption, alkaline phosphatase (AP) activity and the expression of some genes involved in calcium transport in an experimental diabetes model. Two-month old male Wistar rats were divided into two groups: control (n=5) and treated rats (n=5). Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) after fasting for 12-hours. Control rats were injected with the vehicle. Serum and urine glucose were determined before and 5 days after STZ induction. Rats with glycemia over 250 mg/dL were considered diabetic. Intestinal calcium absorption was measured and AP activity from duodenal mucosa was assayed. Ca-ATPase pump and calbindin D28K gene expressions were analyzed by RT-PCR. The weight of the STZ-injected rats decreased after 5 days of the induction and the glucose levels were significantly higher than those of the control group (406±13 mg/dL vs 142±17 mg/dL, p<0.001). Diabetic rats had polyuria and glycosuria. Calcium absorption was lower in diabetic rats than in controls (0.26±0.01 nmol Ca/mL plasma vs 0.65±0.05 nmol Ca/mL plasma, p<0.001). AP activity was significantly lower in diabetic rats than in controls (0.31±0.06 IU/mg protein vs 0.59±0.10 IU/mg protein, p<0.05). Preliminary determinations show that the expression of the studied genes would be similar in both groups. To conclude, the metabolic alteration in DM would alter intestinal calcium absorption and AP activity. The molecular mechanisms responsible of these effects are under investigation. This article is part of a Special Issue entitled AAOMM 2010 Abstracts.

Bone, 2008

and the increas e of SOD activity, produced by MEN treatment, returned to the control values afte... more and the increas e of SOD activity, produced by MEN treatment, returned to the control values after MEL administration. GPX activity and NCX1 and calbindin gene expression were not modified by any treatment. In conclusion, the inhibitory effect of MEN on the intestinal Ca2+absorption is reversed by MEL through the restoration of the GSH content and the SOD activity to the control levels. It is possible that MEL acts as an antioxidant compound leading to an appropriate redox status of enterocytes, which favors that intestinal Ca2+absorption returns to the control values.

Archives of Biochemistry and Biophysics, 2013

The aim of this study was to investigate the effect of ursodeoxycholic acid (UDCA) on intestinal ... more The aim of this study was to investigate the effect of ursodeoxycholic acid (UDCA) on intestinal Ca 2+ absorption and to find out whether the inhibition of this process caused by NaDOC could be prevented by UDCA. Chicks were employed and divided into four groups: (a) controls, (b) treated with 10 mM NaDOC, (c) treated with 60 lg UDCA/100 g of b.w., and (d) treated with 10 mM NaDOC and 60 lg UDCA/100 g of b.w. UDCA enhanced intestinal Ca 2+ absorption, which was time and dose-dependent. UDCA avoided the inhibition of intestinal Ca 2+ absorption caused by NaDOC. Both bile acids altered protein and gene expression of molecules involved in the transcellular pathway of intestinal Ca 2+ absorption, but in the opposite way. UDCA aborted the oxidative stress produced by NaDOC in the intestine. UDCA and UDCA plus NaDOC increased vitamin D receptor protein expression. In conclusion, UDCA is a beneficial bile acid for intestinal Ca 2+ absorption. Contrarily, NaDOC inhibits the intestinal cation absorption through triggering oxidative stress. The use of UDCA in patients with cholestasis would be benefited because of the protective effect on the intestinal Ca 2+ absorption, avoiding the inhibition caused by hydrophobic bile acids and neutralizing the oxidative stress.

Medicina (B. …, 1997

Base de dados : LILACS. Pesquisa : 206750 [Identificador único]. Referências encontradas : 1 [ref... more Base de dados : LILACS. Pesquisa : 206750 [Identificador único]. Referências encontradas : 1 [refinar]. Mostrando: 1 .. 1 no formato [Detalhado]. página 1 de 1, 1 / 1, LILACS, seleciona. para imprimir. Fotocópia. experimental, Documentos relacionados. Id: 206750. ...

High concentrations of sodium deoxycholate (NaDOC) produce toxic effects. This study explores the... more High concentrations of sodium deoxycholate (NaDOC) produce toxic effects. This study explores the effect of a single high concentration of NaDOC on the intestinal Ca 2 + absorption and the underlying mechanisms. Chicks were divided into two groups: 1) controls and 2) treated with different concentrations of NaDOC in the duodenal loop for variable times. Intestinal Ca 2 + absorption was measured as well as the gene and protein expressions of molecules involved in the Ca 2 + transcellular pathway. NaDOC inhibited the intestinal Ca 2 + absorption, which was concentration dependent. Ca 2 +-ATPase mRNA decreased by the bile salt and the same occurred with the protein expression of Ca 2 +-ATPase, calbindin D 28 k and Na + /Ca 2 + exchanger. NaDOC produced oxidative stress as judged by ROS generation, mitochondrial swelling and glutathione depletion. Furthermore, the antioxidant quercetin blocked the inhibitory effect of NaDOC on the intestinal Ca 2 + absorption. Apoptosis was also triggered by the bile salt, as indicated by the TUNEL staining and the cytochrome c release from the mitochondria. As a compensatory mechanism, enzyme activities of the antioxidant system were all increased. In conclusion, a single high concentration of NaDOC inhibits intestinal Ca 2 + absorption through downregulation of proteins involved in the transcellular pathway, as a consequence of oxidative stress and mitochondria mediated apoptosis.

World Journal of Gastroenterology, 2018

Glutathione (GSH) is a tripeptide that constitutes one of the main intracellular reducing compoun... more Glutathione (GSH) is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca 2+ absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K3, sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca 2+ absorption. The GSH depleting drugs switch the redox state towards an oxidant condition provoking oxidative/nitrosative stress and inflammation, which lead to apoptosis and/or autophagy of the enterocytes. Either the transcellular Ca 2+ transport or the paracellular Ca 2+ route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca 2+ pathway are decreased. The flavonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca 2+ absorption, not only by restoration of the GSH levels in the intestine but also by their anti-apoptotic properties. Ursodeoxycholic acid, melatonin and glutamine also block the inhibition of Ca 2+ transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca 2+ absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety, pharmacokinetics and pharmacodynamics of them.

Archives of Biochemistry and Biophysics, 2017

This study tries to elucidate the mechanisms by which fructose rich diets (FRD) inhibit the rat i... more This study tries to elucidate the mechanisms by which fructose rich diets (FRD) inhibit the rat intestinal Ca 2+ absorption, and determine if any or all underlying alterations are prevented by naringin (NAR). Male rats were divided into: 1) controls, 2) treated with FRD, 3) treated with FRD and NAR. The intestinal Ca 2+ absorption and proteins of the transcellular and paracellular Ca 2+ pathways were measured. Oxidative/nitrosative stress and inflammation parameters were evaluated. FRD rats showed inhibition of the intestinal Ca 2+ absorption and decrease in the protein expression of molecules of both Ca 2+ pathways, which were blocked by NAR. FRD rats showed an increase in the superoxide anion, a decrease in the glutathione and in the enzymatic activities of the antioxidant system, as well as an increase in the NO content and in the nitrotyrosine content of proteins. They also exhibited an increase in both IL-6 and nuclear NF-κB. All these changes were prevented by NAR. In conclusion, FRD inhibit both pathways of the intestinal Ca 2+ absorption due to the oxidative/nitrosative stress and inflammation. Since NAR prevents the oxidative/nitrosative stress and inflammation, it might be a drug to avoid alteration in the intestinal Ca 2+ absorption caused by FRD.

Archives of Biochemistry and Biophysics, 2018

The aim of this work was to know whether naringin (NA) could prevent the bone complications in a ... more The aim of this work was to know whether naringin (NA) could prevent the bone complications in a model of streptozotocin (STZ) induced diabetes. Rats were divided in: 1) controls, 2) STZ-rats, 3) STZ-rats treated with 40 mg NA/kg, and 4) STZ-rats treated with 80 mg NA/kg. BMD and BMC were performed by DEXA. Bone histomorphometry and histology as well as TRAP staining were done in tibia. Osteocalcin (OCN) was determined in bone and serum. Glutathione content and SOD and catalase activities were assayed in bone marrow from femur. The data showed that NA80 increased the BMD and BMC from the long bones of STZ-rats. Both NA40 and NA80 normalized the trabecular number and the trabecular separations. An increase in the number of adipocytes and TRAP(+) cells in tibia from STZ-rats was blocked by NA. NA40 treatment increased the number of OCN(+) cells, but only the NA80 treatment allowed to reach the control values. NA normalized the SOD and catalase activities in bone marrow of femur from STZ-rats. In conclusion, NA avoids alterations in the physical properties and microstructure of bone from STZ-rats probably by stimulation of osteoblastogenesis, inhibition of the osteoclastogenesis and adipogenesis via blocking the oxidative stress.

Current medicinal chemistry, Nov 16, 2017

Bile acids (BAs) are synthesized in the liver and are among the main components of bile. For many... more Bile acids (BAs) are synthesized in the liver and are among the main components of bile. For many years, it was thought that they have only a role as emulsifiers of fat in the small intestine facilitating the absorption of lipids and lipid soluble vitamins. Lately, they are also considered important signaling molecules, not only by regulating their own synthesis, but also having a role in several metabolic diseases. In this review we focus on the effect of deoxycholic, ursodeoxycholic and litocholic acids and their combination upon the intestinal Ca2+ absorption. To make the actions of those BAs clear on this physiological process, an overview of current information about the mechanisms by which the intestinal Ca2+ occurs is described. Finally, detailed statements related to the modulation of redox state, apoptosis and autophagy as molecular mechanisms involved in the action of BAs on intestinal Ca2+ absorption are discussed. Although the mechanisms are still not completely understo...

Biochemistry and cell biology = Biochimie et biologie cellulaire, Apr 1, 2017

LCA and 1,25(OH)2D3 are vitamin D receptor ligands with different binding affinity. The secostero... more LCA and 1,25(OH)2D3 are vitamin D receptor ligands with different binding affinity. The secosteroid stimulates intestinal Ca(2+) absorption. Whether LCA alters this process remains unknown. The aim of our work was to determine the effect of LCA on intestinal Ca(2+) absorption in the absence or presence of NaDOC, bile acid that inhibits the cation transport. The data show that LCA by itself did not alter intestinal Ca(2+) absorption, but prevented the inhibitory effect of NaDOC. The concomitant administration of LCA avoided the reduction of intestinal alkaline phosphatase activity caused by NaDOC. In addition, LCA blocked a decrease caused by NaDOC on gene and protein expression of molecules involved in the transcellular pathway of intestinal Ca(2+) absorption. The oxidative stress and apoptosis triggered by NaDOC were abrogated by LCA co-treatment. In conclusion, LCA placed in the intestinal lumen protects intestinal Ca(2+) absorption against the inhibitory effects caused by NaDOC. ...

Archives of Biochemistry and Biophysics, 2016

The aim of this work was to study the effect of sodium deoxycholate (NaDOC) and ursodeoxycholic a... more The aim of this work was to study the effect of sodium deoxycholate (NaDOC) and ursodeoxycholic acid (UDCA) on Ca(2+) uptake by enterocytes and the underlying mechanisms. Rats were divided into four groups: a) controls, b) treated with NaDOC, c) treated with UDCA d) treated with NaDOC and UDCA. Ca(2+) uptake was studied in enterocytes with different degrees of maturation. Apoptosis, autophagy and NO content and iNOS protein expression were evaluated. NaDOC decreased and UDCA increased Ca(2+) uptake only in mature enterocytes. The enhancement of protein expression of Fas, FasL, caspase-8 and caspase-3 activity by NaDOC indicates triggering of the apoptotic extrinsic pathway, which was blocked by UDCA. NO content and iNOS protein expression were enhanced by NaDOC, and avoided by UDCA. The increment of acidic vesicular organelles and LC3 II produced by NaDOC was also prevented by UDCA. In conclusion, the inhibitory effects of NaDOC on intestinal Ca(2+) absorption occur by decreasing the Ca(2+) uptake by mature enterocytes. NaDOC triggers apoptosis and autophagy, in part as a result of nitrosative stress. In contrast, UDCA increases the Ca(2+) uptake by mature enterocytes, and in combination with NaDOC acts as an antiapoptotic and antiautophagic agent normalizing the transcellular Ca(2+) pathway.

Nutrition Research Reviews, 2015

The intestine is the only gate for the entry of Ca to the body in humans and mammals. The entranc... more The intestine is the only gate for the entry of Ca to the body in humans and mammals. The entrance of Ca occurs via paracellular and intracellular pathways. All steps of the latter pathway are regulated by calcitriol and by other hormones. Dietary and pharmacological compounds also modulate the intestinal Ca absorption process. Among them, dietary Ca and P are known to alter the lipid and protein composition of the brush-border and basolateral membranes and, consequently, Ca transport. Ca intakes are below the requirements recommended by health professionals in most countries, triggering important health problems. Chronic low Ca intake has been related to illness conditions such as osteoporosis, hypertension, renal lithiasis and incidences of human cancer. Carbohydrates, mainly lactose, and prebiotics have been described as positive modulators of intestinal Ca absorption. Apparently, high meat proteins increase intestinal Ca absorption while the effect of dietary lipids remains uncl...

Biochimica et biophysica acta, 2015

The aim was to determine the intestinal Ca(2+) absorption in type I diabetic rats after different... more The aim was to determine the intestinal Ca(2+) absorption in type I diabetic rats after different times of STZ induction, as well as the gene and protein expression of molecules involved in both the transcellular and paracellular Ca(2+) pathways. The redox state and the antioxidant enzymes of the enterocytes were also evaluated in duodenum from either diabetic or insulin-treated diabetic rats as compared to control rats. Male Wistar rats (150-200g) were divided into two groups: 1) controls and 2) STZ-induced diabetic rats (60mg/kg b.w.). A group of diabetic rats received insulin for five days. The insulin was adjusted daily to maintain a normal blood glucose level. Five 5 d after STZ injection, there was a reduction in the intestinal Ca(2+) absorption, which was maintained for 30 d and disappeared at 60 d. Similar changes occurred in the GSH and (˙)O2(-) levels. The protein expression of molecules involved in the transcellular pathway increased at 5 and 30 d returning to control val...

Melatonin and Melatonergic Drugs in Clinical Practice, 2013

Melatonin (MEL) is a pleiotropic hormone which exerts its action through different mechanisms, ei... more Melatonin (MEL) is a pleiotropic hormone which exerts its action through different mechanisms, either by binding to its receptors or by acting as an antioxidant molecule and ROS scavenger. Its mechanisms of action together with the wide distribution of MT1 and MT2 receptors have provoked an ever-increasing number of clinical trials in the last two decades. These studies have evaluated the exogenous administration of MEL in different doses and formulations to prevent or to treat many health disorders. The predominant field of research has been the treatment of insomnia and other circadian rhythm disorders due to the confirmed resynchronizing properties of this indolamine. However, in the last decade, a profound interest has arisen concerning its potential therapeutic value in different conditions such as cancer, cardiovascular diseases, gastrointestinal problems, and inflammatory states, among others. The relatively low toxicity of MEL over a wide range of doses has made the research even more promising. However, new multicenter clinical trials could shed light on different aspects of MEL’s clinical uses contributing thus to clarify the conditions in which MEL might be considered as a first-line therapeutical strategy and to identify when the combination of MEL with other drugs is necessary. In this chapter, we revise the milestones in the field of MEL research from its discovery to the present time and analyze the future perspectives of its clinical uses.

Journal of Bone and Mineral Metabolism, 2008

The aim of this study was to determine genotypes and clinical aspects associated with bone minera... more The aim of this study was to determine genotypes and clinical aspects associated with bone mineral density (BMD) in postmenopausal women from Córdoba, Argentina. Polymorphisms were assessed by RFLP-PCR technique using BsmI and FokI for vitamin D receptor gene (VDR) and XbaI and PvuII for estrogen receptor-alpha gene (ERalpha) as restrictases. Sixty-eight healthy, 54 osteopenic, and 64 osteoporotic postmenopausal women were recruited. Femoral neck and lumbar spine BMD were inversely correlated with age in the entire analyzed population. Height was lower in osteopenic and osteoporotic women as compared to healthy women (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Weight and body mass index (BMI) were the lowest in osteoporotic women (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01 versus healthy group). Serum procollagen type I Nterminal propeptide (PINP) was higher in osteoporotic women as compared to the other groups. Distribution of VDR and ERalpha genotypes was similar in the three groups. Genotype bb (VDR) was associated with low values of lumbar BMD in the healthy group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05 versus genotype Bb), and with low values of femoral BMD (P…

Digestion, 2008

An overview of current information on the mechanisms by which intestinal calcium absorption occur... more An overview of current information on the mechanisms by which intestinal calcium absorption occurs is described in this article. Both paracellular and transcellular pathways are analyzed. Special emphasis focuses on molecules participating in the latter pathway, such as TRPV5 and TRPV6 channels, located in the apical region of the enterocytes, CB9k and CB28k, presumably involved in the cation movement from the apical to the basolateral pole of the cell, and PMCA1b and Na+/Ca2+ exchanger, proteins that extrude Ca2+ from the cells. Current concepts on the relative importance of paracellular and transcellular calcium transport and the vitamin D dependence of each pathway are referred and analyzed showing the contrasting views on this issue. More detailed information is given regarding the stimulatory effect of vitamin D on intestinal Ca2+ absorption either in animal models or in the human intestine. The possible mechanisms triggered by hormones such as PTH, calcitonin, estrogen, thyroi...

Bone, 2011

Diabetes mellitus (DM) type I is a disorder characterized by hyperglycemia due to a deficient ins... more Diabetes mellitus (DM) type I is a disorder characterized by hyperglycemia due to a deficient insulin secretion. Alterations in different organs have been observed in DM. The aim of this work was to study intestinal calcium absorption, alkaline phosphatase (AP) activity and the expression of some genes involved in calcium transport in an experimental diabetes model. Two-month old male Wistar rats were divided into two groups: control (n=5) and treated rats (n=5). Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) after fasting for 12-hours. Control rats were injected with the vehicle. Serum and urine glucose were determined before and 5 days after STZ induction. Rats with glycemia over 250 mg/dL were considered diabetic. Intestinal calcium absorption was measured and AP activity from duodenal mucosa was assayed. Ca-ATPase pump and calbindin D28K gene expressions were analyzed by RT-PCR. The weight of the STZ-injected rats decreased after 5 days of the induction and the glucose levels were significantly higher than those of the control group (406±13 mg/dL vs 142±17 mg/dL, p<0.001). Diabetic rats had polyuria and glycosuria. Calcium absorption was lower in diabetic rats than in controls (0.26±0.01 nmol Ca/mL plasma vs 0.65±0.05 nmol Ca/mL plasma, p<0.001). AP activity was significantly lower in diabetic rats than in controls (0.31±0.06 IU/mg protein vs 0.59±0.10 IU/mg protein, p<0.05). Preliminary determinations show that the expression of the studied genes would be similar in both groups. To conclude, the metabolic alteration in DM would alter intestinal calcium absorption and AP activity. The molecular mechanisms responsible of these effects are under investigation. This article is part of a Special Issue entitled AAOMM 2010 Abstracts.

Bone, 2008

and the increas e of SOD activity, produced by MEN treatment, returned to the control values afte... more and the increas e of SOD activity, produced by MEN treatment, returned to the control values after MEL administration. GPX activity and NCX1 and calbindin gene expression were not modified by any treatment. In conclusion, the inhibitory effect of MEN on the intestinal Ca2+absorption is reversed by MEL through the restoration of the GSH content and the SOD activity to the control levels. It is possible that MEL acts as an antioxidant compound leading to an appropriate redox status of enterocytes, which favors that intestinal Ca2+absorption returns to the control values.

Archives of Biochemistry and Biophysics, 2013

The aim of this study was to investigate the effect of ursodeoxycholic acid (UDCA) on intestinal ... more The aim of this study was to investigate the effect of ursodeoxycholic acid (UDCA) on intestinal Ca 2+ absorption and to find out whether the inhibition of this process caused by NaDOC could be prevented by UDCA. Chicks were employed and divided into four groups: (a) controls, (b) treated with 10 mM NaDOC, (c) treated with 60 lg UDCA/100 g of b.w., and (d) treated with 10 mM NaDOC and 60 lg UDCA/100 g of b.w. UDCA enhanced intestinal Ca 2+ absorption, which was time and dose-dependent. UDCA avoided the inhibition of intestinal Ca 2+ absorption caused by NaDOC. Both bile acids altered protein and gene expression of molecules involved in the transcellular pathway of intestinal Ca 2+ absorption, but in the opposite way. UDCA aborted the oxidative stress produced by NaDOC in the intestine. UDCA and UDCA plus NaDOC increased vitamin D receptor protein expression. In conclusion, UDCA is a beneficial bile acid for intestinal Ca 2+ absorption. Contrarily, NaDOC inhibits the intestinal cation absorption through triggering oxidative stress. The use of UDCA in patients with cholestasis would be benefited because of the protective effect on the intestinal Ca 2+ absorption, avoiding the inhibition caused by hydrophobic bile acids and neutralizing the oxidative stress.

Medicina (B. …, 1997

Base de dados : LILACS. Pesquisa : 206750 [Identificador único]. Referências encontradas : 1 [ref... more Base de dados : LILACS. Pesquisa : 206750 [Identificador único]. Referências encontradas : 1 [refinar]. Mostrando: 1 .. 1 no formato [Detalhado]. página 1 de 1, 1 / 1, LILACS, seleciona. para imprimir. Fotocópia. experimental, Documentos relacionados. Id: 206750. ...

High concentrations of sodium deoxycholate (NaDOC) produce toxic effects. This study explores the... more High concentrations of sodium deoxycholate (NaDOC) produce toxic effects. This study explores the effect of a single high concentration of NaDOC on the intestinal Ca 2 + absorption and the underlying mechanisms. Chicks were divided into two groups: 1) controls and 2) treated with different concentrations of NaDOC in the duodenal loop for variable times. Intestinal Ca 2 + absorption was measured as well as the gene and protein expressions of molecules involved in the Ca 2 + transcellular pathway. NaDOC inhibited the intestinal Ca 2 + absorption, which was concentration dependent. Ca 2 +-ATPase mRNA decreased by the bile salt and the same occurred with the protein expression of Ca 2 +-ATPase, calbindin D 28 k and Na + /Ca 2 + exchanger. NaDOC produced oxidative stress as judged by ROS generation, mitochondrial swelling and glutathione depletion. Furthermore, the antioxidant quercetin blocked the inhibitory effect of NaDOC on the intestinal Ca 2 + absorption. Apoptosis was also triggered by the bile salt, as indicated by the TUNEL staining and the cytochrome c release from the mitochondria. As a compensatory mechanism, enzyme activities of the antioxidant system were all increased. In conclusion, a single high concentration of NaDOC inhibits intestinal Ca 2 + absorption through downregulation of proteins involved in the transcellular pathway, as a consequence of oxidative stress and mitochondria mediated apoptosis.