Claudio Mannari - Academia.edu (original) (raw)
Papers by Claudio Mannari
International Journal of Immunopathology and Pharmacology, Oct 1, 2005
In this study, we investigated the effect of 1,25(OH) zD3 on proteinuria and on the alteration of... more In this study, we investigated the effect of 1,25(OH) zD3 on proteinuria and on the alteration of slit diaphragm-associated proteins induced by anti-Thy 1.1 in Wistar rats. Four groups of animals were studied: group I, anti-Thy 1.1 treated rats; group II, anti-Thy1.1 treated group that at day 2, after the onset of overt proteinuria, started the treatment with 1,25(OH) zD3 ; group ill, normal control rats injected with vehicle alone; group~rats that received only 1,25(OH) zD3 • At day 2, in group I and II, before the administration of 1,25(OH) zD3 , protein excretion was significantly increased when compared to controls. Overt proteinuria was maintained until day 14 in group I whereas in group II protein excretion was significantly reduced from day 3 to day 14. Moreover, treatment with 1,25(OH) zD3abrogated podocytes injury, detected as desmin expression and loss ofnephrin and zonula occludens-l (ZO-I), two slit diaphragm-associated proteins, and glomerular polyanion staining, that were observed in group I. In conclusion, these results suggest that 1,25(OH) zD3 administrated with a therapeutic regiment may revert proteinuria, counteracting glomerular podocyte injury. Severalstudiesindicated that 1,25-Dihydroxyvitamin glomerular growth and glomerulosclerosis in a model D 3 (1,25-(OH)2D3) may affect cell proliferation and of subtotal nephrectomy (9). Therefore, 1,25-(OH)2D3 differentiation (1-2), and immune response (3-4). seems to inhibit proteinuria in different experimental Anti-proteinuric and anti-inflammatory effects of models independently from the initial pathogenic 1,25-(OH)2D3 have been shown in different experimental mechanism. These observations prompt us to models of glomerular injury including Heymann investigate the mechanism of anti-proteinuric effect of nephritis (5), mercuric chloride-induced autoimmune 1,25-(OH)2D3' disease in BN rats (6), and spontaneous lupus in Recent studies focused on a central role of the MRL/L mice (7). Moreover, we demonstrated that podocyte slit diaphragm in maintaining the 1,25-(OH)2D3administration reduced proteinuria, as glomerular permeability (10). In particular, the well as recruitment of inflammatory cells and functional role of slit diaphragm-associated proteins mesangial proliferation, in the anti-Thy-I. l-induced such as nephrin, podocin, CD2-associated protein, glomerulonephritis (GN) in rats (8). 1,25-(OH)2D3 was alpha-actin 4 and nephl in maintaining the sizealso shown to reduce proteinuria, cell proliferation, selective barrier has been defined (11). Besides
Archives of Animal Nutrition, Jun 1, 2013
The study evaluated the partial substitution of soybean meal by faba beans (18%) or peas (20%) as... more The study evaluated the partial substitution of soybean meal by faba beans (18%) or peas (20%) as additional protein sources in diets destined for typical Italian heavy pig production. It compared animal performances, meat quality, the presence of residual anti-nutritional factors (ANF) and phytoestrogens in plasma and meat and the possible effects on pig health, by evaluating oxidative, inflammatory and pro-atherogenic markers. The results showed that the productive performances, expressed as body weight and feed conversion ratio, of pigs fed with faba bean and pea diets were similar to those of pigs fed only the soybean meal. Meat quality of pigs fed with the three diets was similar in colour, water-holding capacity, tenderness and chemical composition. Despite the higher levels of phytoestrogen in the plasma of pigs fed only the soybean meal, phytoestrogen concentration in the muscle was equivalent to that of animals fed diets with faba beans, whereas pigs fed a diet with peas showed a lower concentration. Inflammation and pro-atherogenic parameters did not show significant differences among the three diets. Overall, the partial substitution of soybean meal by faba beans appears more interesting than with peas, particularly in relation to the higher amount of polyphenols in the diet and the highest concentration of phytoestrogens found in the plasma and muscle of animals, while the pyrimidine anti-nutritional compounds present in the diet did not appear to accumulate and had no effect on the growth performance of animals.
European journal of nutrition, 2011
PLOS ONE, 2015
<p>Ach stimulation increased NO release, revealed by chemiluminescence. TYR 1μM and 100nM d... more <p>Ach stimulation increased NO release, revealed by chemiluminescence. TYR 1μM and 100nM did not affect Ach-induced NO release (Fig. 1A); CAF enhanced Ach-induced NO release in a dose-dependent manner (Fig. 1B) (p<0.05 CAF vs. controls or vs. Ach at all time points considered). Results are expressed as average±1SD of 6 different experiments.</p
Endothelial progenitor cells are known to reverse acute kidney injury by paracrine mechanisms. We... more Endothelial progenitor cells are known to reverse acute kidney injury by paracrine mechanisms. We previously found that microvesicles released from these progenitor cells activate an angiogenic program in endothelial cells by horizontal mRNA transfer. Here, we tested whether these microvesicles prevent acute kidney injury in a rat model of ischemia-reperfusion injury. The RNA content of microvesicles was enriched in microRNAs (miRNAs) that modulate proliferation, angiogenesis, and apoptosis. After intravenous injection following ischemia-reperfusion, the microvesicles were localized within peritubular capillaries and tubular cells. This conferred functional and morphologic protection from acute kidney injury by enhanced tubular cell proliferation, reduced apoptosis, and leukocyte infiltration. Microvesicles also protected against progression of chronic kidney damage by inhibiting capillary rarefaction, glomerulosclerosis, and tubulointerstitial fibrosis. The renoprotective effect of microvesicles was lost after treatment with RNase, nonspecific miRNA depletion of microvesicles by Dicer knock-down in the progenitor cells, or depletion of pro-angiogenic miR-126 and miR-296 by transfection with specific miR-antagomirs. Thus, microvesicles derived from endothelial progenitor cells protect the kidney from ischemic acute injury by delivering their RNA content, the miRNA cargo of which contributes to reprogramming hypoxic resident renal cells to a regenerative program.
☯ These authors contributed equally to this work.
International Journal of Immunopathology and Pharmacology, 2005
In this study, we investigated the effect of 1,25(OH)2D3on proteinuria and on the alteration of s... more In this study, we investigated the effect of 1,25(OH)2D3on proteinuria and on the alteration of slit diaphragm-associated proteins induced by anti-Thy 1.1 in Wistar rats. Four groups of animals were studied: group I, anti-Thy 1.1 treated rats; group II, anti-Thy1.1 treated group that at day 2, after the onset of overt proteinuria, started the treatment with 1,25(OH)2D3; group III, normal control rats injected with vehicle alone; group IV, rats that received only 1,25(OH)2D3. At day 2, in group I and II, before the administration of 1,25(OH)2D3, protein excretion was significantly increased when compared to controls. Overt proteinuria was maintained until day 14 in group I whereas in group II protein excretion was significantly reduced from day 3 to day 14. Moreover, treatment with 1,25(OH)2D3abrogated podocytes injury, detected as desmin expression and loss of nephrin and zonula occludens-1 (ZO-1), two slit diaphragm-associated proteins, and glomerular polyanion staining, that were ...
Biomedicine & Pharmacotherapy, 2016
Although many studies highlight how long-term moderate dose of Recombinant Human Erythropoietin (... more Although many studies highlight how long-term moderate dose of Recombinant Human Erythropoietin (rHuEPO) treatments result in beneficial and antioxidants effects, few studies take into account the effects that short-term high doses of rHuEPO (mimicking abuse conditions) might have on the oxidative stress processes. Thus, the aim of this study was to investigate the in vivo antioxidant activity of rHuEPO, administered for a short time and at high doses to mimic its sports abuse as doping. Male Wistar healthy rats (n = 36) were recruited for the study and were treated with three different concentrations of rHuEPO: 7.5, 15, 30 mg/kg. Plasma concentrations of erythropoietin, 8-epi Prostaglandin F 2a, plasma and urinary concentrations of NOx were evaluated with specific assay kit, while hematocrit levels were analyzed with an automated cell counter. Antioxidant activity of rHuEPO was assessed analyzing the possible variation of the plasma scavenger capacity against hydroxylic and peroxylic radicals by TOSC (Total Oxyradical Scavenging Capacity) assay. Statistical analyses showed higher hematocrit values, confirmed by a statistically significant increase of plasmatic EPO concentration. An increase in plasma scavenging capacity against peroxyl and hydroxyl radicals, in 8-isoprostane plasmatic concentrations and in plasmatic and urinary levels of NO X were also found in all the treated animals, though not always statistically significant. Our results confirm the literature data regarding the antioxidant action of erythropoietin administered at low doses and for short times, whereas they showed an opposite incremental oxidative stress action when erythropoietin is administered at high doses. 2016 Elsevier Masson SAS. All rights reserved.
Transplantation, 2008
Ischemia/reperfusion tolerance is important in kidney transplantation. Erythropoietin inhibits ap... more Ischemia/reperfusion tolerance is important in kidney transplantation. Erythropoietin inhibits apoptosis and infl ammation, and provides renoprotection. This study investigated the effects of different preservation methods on reperfusion tolerance of kidneys. Porcine kidneys subjected to 10-minutes ischemia were preserved by four approaches: 16-hours cold storage (CS) followed by 2-hours warm preservation (WP) ± 5000 units/L erythropoietin; or 18-hours CS ± 5000 units/L erythropoietin, and assessed by haemoreperfusion for 3 hours on an isolated organ perfusion system. All parameters were measured on termination of CS, WP and reperfusion. Both WP and reperfusion increased caspase-3 activity, the expression of heat shock protein 70, apoptosis in tubular areas (excluding kidneys preserved by 18-hours CS), tubular lumens and the interstitium compared with CS kidneys. The presence of erythropoietin in WP further raised caspase-3 activity and apoptosis in tubular lumens, sustained interstitial apoptosis and reduced tubular apoptosis; also subsequently improved tubular vacuolation and interstitial expansion, oxygen consumption and renal blood fl ow after reperfusion. Erythropoietin increased urine production more than renal blood fl ow. WP and erythropoietin improved reperfusion tolerance and early renal structure and function over that seen in CS alone. This was probably through caspase-3 activation, HSP70 induction and subsequently improved clearance of infl ammation and damaged cells.
Journal of Affective Disorders
Plant Foods for Human Nutrition, 2012
The cardioprotective and anti-aging effects of red wine phenols, especially resveratrol (RSV), ar... more The cardioprotective and anti-aging effects of red wine phenols, especially resveratrol (RSV), are well known. One of the most interesting biological properties of RSV and other naturally occurring phenols is the regulation of the expression and activity of SIRT1 (silent mating type information regulation 2 homolog). In view of the role of SIRT1 in acute and chronic renal diseases, we decided to study the effects of RSV-poor red wines on the expression of SIRT1 and HIF-2α (hypoxia-inducible factor 2α) to be compared with a nanomolar concentration of RSV or malvidin in proximal tubular cells of human kidneys (PTEC). Survival signaling systems activation (extracellular signal-regulated kinases, ERK and AMP-activated protein kinase, AMPK) was also investigated in PTEC incubated with wines. PTEC cells were incubated in the presence of RSV-poor wines diluted 1:1,000 for 30′, 90′, 120′ and 24 h. Expression of SIRT1 and HIF-2α, and activation of ERK and AMPK were analyzed by Western Blot. The data obtained show that wine modulates the expression of anti-aging molecular systems even when RSV is present in very small amounts.
Nephrology Dialysis Transplantation, 2014
Background. Endothelial progenitor cells (EPCs) are known to induce tissue repair by paracrine me... more Background. Endothelial progenitor cells (EPCs) are known to induce tissue repair by paracrine mechanisms including the release of growth factors and extracellular vesicles (EVs), nanoparticles able to carry proteins and genetic information to target cells. The aim of this study was to evaluate whether EVs derived from EPCs may protect from complement-mediated mesangial injury in experimental anti-Thy1.1 glomerulonephritis. Methods. EVs were isolated by serial ultracentrifugation from supernatants of cultured human EPCs and characterized for their protein and RNA content. In vivo, EVs were injected i.v. in the experimental rat model of mesangiolytic anti-Thy1.1 glomerulonephritis evaluating renal function, proteinuria, complement activity and histological lesions. In vitro, the biological effects of EPC-derived EVs were studied in cultured rat mesangial cells incubated with anti-Thy1.1 antibody and rat or human serum as complement source. Results. After i.v. injection in Thy1.1-treated rats, EVs localized within injured glomeruli and inhibited mesangial cell activation, leucocyte infiltration and apoptosis, decreased proteinuria, increased serum complement haemolytic activity (CH50) and ameliorated renal function. EV treatment decreased intraglomerular deposition of the membrane attack complex (MAC or C5b-9) and expression of smooth muscle cell actin and preserved the endothelial antigen RECA-1 and the podocyte marker synaptopodin. The protective effect of EVs was significantly reduced by pre-treatment with a high dose of RNase (1 U/mL), suggesting a key role for EV-carried RNAs in these mechanisms. Indeed, EPC-derived EVs contained different mRNAs coding for several anti-apoptotic molecules and for the complement inhibitors Factor H, CD55 and CD59 and the related proteins. The in vitro experiments aimed to investigate the mechanisms of EV protection indicated that EVs transferred to mesangial cell mRNAs coding for Factor H, CD55 and CD59 and inhibited anti-Thy1.1 antibody/complement-induced apoptosis and C5b-9/C3 mesangial cell deposition. Conclusions. EVs derived from EPCs exert a protective effect in Thy1.1 glomerulonephritis by inhibition of antibody-and complement-mediated injury of mesangial cells.
Micron (Oxford, England : 1993), 2014
In recent years, human dental pulp stromal cells (DPSCs) have received growing attention due to t... more In recent years, human dental pulp stromal cells (DPSCs) have received growing attention due to their characteristics in common with other mesenchymal stem cells, in addition to the ease with which they can be harvested. In this study, we demonstrated that the isolation of DPSCs from third molar teeth of healthy individuals allowed the recovery of dental mesenchymal stem cells that showed self-renewal and multipotent differentiation capability. DPSCs resulted positive for CD73, CD90, CD105, STRO-1, negative for CD34, CD45, CD14 and were able to differentiate into osteogenic and chondrogenic cells. We also assayed the angiogenic potential of DPSCs, their capillary tube-like formation was assessed using an in vitro angiogenesis assay and the uptake of acetylated low-density lipoprotein was measured as a marker of endothelial function. Based on these results, DPSCs were capable of differentiating into cells with phenotypic and functional features of endothelial cells. Furthermore, this...
Journal of Agricultural and Food Chemistry, 2005
Ochratoxin A (OTA), is a nephrotoxic mycotoxin present in wine, which is nephrotoxic in humans. O... more Ochratoxin A (OTA), is a nephrotoxic mycotoxin present in wine, which is nephrotoxic in humans. Our working hypothesis is that natural substances in wine may counteract OTA toxicity. Thirty-six rats were randomized to OTA dissolved in saline, red wine, or 13.5% ethanol or to OTA-free wine, ethanol, or saline. OTA (289 µg/kg of body weight/48 h) was administered by gastric gavage for 2 weeks. Serum creatinine, tubular enzymuria, renal lipohydroperoxides (LOOH), reduced (GSH) and oxidized (GSSG) glutathione, and renal superoxide dismutase activity (SOD) were determined in renal tissue. OTA alone produced significant increases in renal lipoperoxides and significant decreases in SOD and GSH/GSSG ratio. In red wine or ethanol, OTA was less nephrotoxic, reducing oxidative damage as revealed by LOOH. In OTA-wine and OTA-ethanol groups, SOD activity was higher than in the OTA-treated one, suggesting that both ethanol and nonalcoholic fractions may preserve antioxidant reserve. GSH/GSSG ratio was significantly preserved only in the OTA-wine group and not in OTA-ethanol. Red wine may exert a protective effect against OTA nephrotoxicity by limiting oxidative damage. The ostensible protection afforded by ethanol deserves further investigation.
Journal of Affective Disorders, 2008
Background: Brain-derived neurotrophic factor (BDNF) has been hypothesized to be involved in the ... more Background: Brain-derived neurotrophic factor (BDNF) has been hypothesized to be involved in the neurobiology of major depression. The aim of this study was to assess the possible relationships between depressive symptoms and serum and/or plasma BDNF levels during 1 year of antidepressant treatment. Methods: Plasma and serum BDNF levels were assayed in 15 drug-free depressed patients and in 15 healthy control subjects at baseline and the 1st, 3rd, 6th and 12th month of antidepressant treatment. Results: At baseline, patients' serum and plasma BDNF levels were significantly lower (p b .001 and p = .004, respectively) than those found in healthy control subjects. However, while from the 1st month of treatment patients' plasma BDNF levels did not differ significantly from those observed in healthy control subjects, serum BDNF levels in patients remained significantly lower at all times. Limitations: The main limitations of the current study are represented by the small sample size and the high discontinuation rate. Conclusions: Untreated depressed patients showed reduced baseline serum and plasma BDNF levels, as compared with control subjects. The clinical improvement paralleled the normalization of plasma BDNF after 1 month of treatment, while, at every assessment time, patients' serum BDNF levels were lower than those of control subjects. This would suggest that serum BDNF might represent a non-specific trait marker of depression.
International Journal of Immunopathology and Pharmacology, Oct 1, 2005
In this study, we investigated the effect of 1,25(OH) zD3 on proteinuria and on the alteration of... more In this study, we investigated the effect of 1,25(OH) zD3 on proteinuria and on the alteration of slit diaphragm-associated proteins induced by anti-Thy 1.1 in Wistar rats. Four groups of animals were studied: group I, anti-Thy 1.1 treated rats; group II, anti-Thy1.1 treated group that at day 2, after the onset of overt proteinuria, started the treatment with 1,25(OH) zD3 ; group ill, normal control rats injected with vehicle alone; group~rats that received only 1,25(OH) zD3 • At day 2, in group I and II, before the administration of 1,25(OH) zD3 , protein excretion was significantly increased when compared to controls. Overt proteinuria was maintained until day 14 in group I whereas in group II protein excretion was significantly reduced from day 3 to day 14. Moreover, treatment with 1,25(OH) zD3abrogated podocytes injury, detected as desmin expression and loss ofnephrin and zonula occludens-l (ZO-I), two slit diaphragm-associated proteins, and glomerular polyanion staining, that were observed in group I. In conclusion, these results suggest that 1,25(OH) zD3 administrated with a therapeutic regiment may revert proteinuria, counteracting glomerular podocyte injury. Severalstudiesindicated that 1,25-Dihydroxyvitamin glomerular growth and glomerulosclerosis in a model D 3 (1,25-(OH)2D3) may affect cell proliferation and of subtotal nephrectomy (9). Therefore, 1,25-(OH)2D3 differentiation (1-2), and immune response (3-4). seems to inhibit proteinuria in different experimental Anti-proteinuric and anti-inflammatory effects of models independently from the initial pathogenic 1,25-(OH)2D3 have been shown in different experimental mechanism. These observations prompt us to models of glomerular injury including Heymann investigate the mechanism of anti-proteinuric effect of nephritis (5), mercuric chloride-induced autoimmune 1,25-(OH)2D3' disease in BN rats (6), and spontaneous lupus in Recent studies focused on a central role of the MRL/L mice (7). Moreover, we demonstrated that podocyte slit diaphragm in maintaining the 1,25-(OH)2D3administration reduced proteinuria, as glomerular permeability (10). In particular, the well as recruitment of inflammatory cells and functional role of slit diaphragm-associated proteins mesangial proliferation, in the anti-Thy-I. l-induced such as nephrin, podocin, CD2-associated protein, glomerulonephritis (GN) in rats (8). 1,25-(OH)2D3 was alpha-actin 4 and nephl in maintaining the sizealso shown to reduce proteinuria, cell proliferation, selective barrier has been defined (11). Besides
Archives of Animal Nutrition, Jun 1, 2013
The study evaluated the partial substitution of soybean meal by faba beans (18%) or peas (20%) as... more The study evaluated the partial substitution of soybean meal by faba beans (18%) or peas (20%) as additional protein sources in diets destined for typical Italian heavy pig production. It compared animal performances, meat quality, the presence of residual anti-nutritional factors (ANF) and phytoestrogens in plasma and meat and the possible effects on pig health, by evaluating oxidative, inflammatory and pro-atherogenic markers. The results showed that the productive performances, expressed as body weight and feed conversion ratio, of pigs fed with faba bean and pea diets were similar to those of pigs fed only the soybean meal. Meat quality of pigs fed with the three diets was similar in colour, water-holding capacity, tenderness and chemical composition. Despite the higher levels of phytoestrogen in the plasma of pigs fed only the soybean meal, phytoestrogen concentration in the muscle was equivalent to that of animals fed diets with faba beans, whereas pigs fed a diet with peas showed a lower concentration. Inflammation and pro-atherogenic parameters did not show significant differences among the three diets. Overall, the partial substitution of soybean meal by faba beans appears more interesting than with peas, particularly in relation to the higher amount of polyphenols in the diet and the highest concentration of phytoestrogens found in the plasma and muscle of animals, while the pyrimidine anti-nutritional compounds present in the diet did not appear to accumulate and had no effect on the growth performance of animals.
European journal of nutrition, 2011
PLOS ONE, 2015
<p>Ach stimulation increased NO release, revealed by chemiluminescence. TYR 1μM and 100nM d... more <p>Ach stimulation increased NO release, revealed by chemiluminescence. TYR 1μM and 100nM did not affect Ach-induced NO release (Fig. 1A); CAF enhanced Ach-induced NO release in a dose-dependent manner (Fig. 1B) (p<0.05 CAF vs. controls or vs. Ach at all time points considered). Results are expressed as average±1SD of 6 different experiments.</p
Endothelial progenitor cells are known to reverse acute kidney injury by paracrine mechanisms. We... more Endothelial progenitor cells are known to reverse acute kidney injury by paracrine mechanisms. We previously found that microvesicles released from these progenitor cells activate an angiogenic program in endothelial cells by horizontal mRNA transfer. Here, we tested whether these microvesicles prevent acute kidney injury in a rat model of ischemia-reperfusion injury. The RNA content of microvesicles was enriched in microRNAs (miRNAs) that modulate proliferation, angiogenesis, and apoptosis. After intravenous injection following ischemia-reperfusion, the microvesicles were localized within peritubular capillaries and tubular cells. This conferred functional and morphologic protection from acute kidney injury by enhanced tubular cell proliferation, reduced apoptosis, and leukocyte infiltration. Microvesicles also protected against progression of chronic kidney damage by inhibiting capillary rarefaction, glomerulosclerosis, and tubulointerstitial fibrosis. The renoprotective effect of microvesicles was lost after treatment with RNase, nonspecific miRNA depletion of microvesicles by Dicer knock-down in the progenitor cells, or depletion of pro-angiogenic miR-126 and miR-296 by transfection with specific miR-antagomirs. Thus, microvesicles derived from endothelial progenitor cells protect the kidney from ischemic acute injury by delivering their RNA content, the miRNA cargo of which contributes to reprogramming hypoxic resident renal cells to a regenerative program.
☯ These authors contributed equally to this work.
International Journal of Immunopathology and Pharmacology, 2005
In this study, we investigated the effect of 1,25(OH)2D3on proteinuria and on the alteration of s... more In this study, we investigated the effect of 1,25(OH)2D3on proteinuria and on the alteration of slit diaphragm-associated proteins induced by anti-Thy 1.1 in Wistar rats. Four groups of animals were studied: group I, anti-Thy 1.1 treated rats; group II, anti-Thy1.1 treated group that at day 2, after the onset of overt proteinuria, started the treatment with 1,25(OH)2D3; group III, normal control rats injected with vehicle alone; group IV, rats that received only 1,25(OH)2D3. At day 2, in group I and II, before the administration of 1,25(OH)2D3, protein excretion was significantly increased when compared to controls. Overt proteinuria was maintained until day 14 in group I whereas in group II protein excretion was significantly reduced from day 3 to day 14. Moreover, treatment with 1,25(OH)2D3abrogated podocytes injury, detected as desmin expression and loss of nephrin and zonula occludens-1 (ZO-1), two slit diaphragm-associated proteins, and glomerular polyanion staining, that were ...
Biomedicine & Pharmacotherapy, 2016
Although many studies highlight how long-term moderate dose of Recombinant Human Erythropoietin (... more Although many studies highlight how long-term moderate dose of Recombinant Human Erythropoietin (rHuEPO) treatments result in beneficial and antioxidants effects, few studies take into account the effects that short-term high doses of rHuEPO (mimicking abuse conditions) might have on the oxidative stress processes. Thus, the aim of this study was to investigate the in vivo antioxidant activity of rHuEPO, administered for a short time and at high doses to mimic its sports abuse as doping. Male Wistar healthy rats (n = 36) were recruited for the study and were treated with three different concentrations of rHuEPO: 7.5, 15, 30 mg/kg. Plasma concentrations of erythropoietin, 8-epi Prostaglandin F 2a, plasma and urinary concentrations of NOx were evaluated with specific assay kit, while hematocrit levels were analyzed with an automated cell counter. Antioxidant activity of rHuEPO was assessed analyzing the possible variation of the plasma scavenger capacity against hydroxylic and peroxylic radicals by TOSC (Total Oxyradical Scavenging Capacity) assay. Statistical analyses showed higher hematocrit values, confirmed by a statistically significant increase of plasmatic EPO concentration. An increase in plasma scavenging capacity against peroxyl and hydroxyl radicals, in 8-isoprostane plasmatic concentrations and in plasmatic and urinary levels of NO X were also found in all the treated animals, though not always statistically significant. Our results confirm the literature data regarding the antioxidant action of erythropoietin administered at low doses and for short times, whereas they showed an opposite incremental oxidative stress action when erythropoietin is administered at high doses. 2016 Elsevier Masson SAS. All rights reserved.
Transplantation, 2008
Ischemia/reperfusion tolerance is important in kidney transplantation. Erythropoietin inhibits ap... more Ischemia/reperfusion tolerance is important in kidney transplantation. Erythropoietin inhibits apoptosis and infl ammation, and provides renoprotection. This study investigated the effects of different preservation methods on reperfusion tolerance of kidneys. Porcine kidneys subjected to 10-minutes ischemia were preserved by four approaches: 16-hours cold storage (CS) followed by 2-hours warm preservation (WP) ± 5000 units/L erythropoietin; or 18-hours CS ± 5000 units/L erythropoietin, and assessed by haemoreperfusion for 3 hours on an isolated organ perfusion system. All parameters were measured on termination of CS, WP and reperfusion. Both WP and reperfusion increased caspase-3 activity, the expression of heat shock protein 70, apoptosis in tubular areas (excluding kidneys preserved by 18-hours CS), tubular lumens and the interstitium compared with CS kidneys. The presence of erythropoietin in WP further raised caspase-3 activity and apoptosis in tubular lumens, sustained interstitial apoptosis and reduced tubular apoptosis; also subsequently improved tubular vacuolation and interstitial expansion, oxygen consumption and renal blood fl ow after reperfusion. Erythropoietin increased urine production more than renal blood fl ow. WP and erythropoietin improved reperfusion tolerance and early renal structure and function over that seen in CS alone. This was probably through caspase-3 activation, HSP70 induction and subsequently improved clearance of infl ammation and damaged cells.
Journal of Affective Disorders
Plant Foods for Human Nutrition, 2012
The cardioprotective and anti-aging effects of red wine phenols, especially resveratrol (RSV), ar... more The cardioprotective and anti-aging effects of red wine phenols, especially resveratrol (RSV), are well known. One of the most interesting biological properties of RSV and other naturally occurring phenols is the regulation of the expression and activity of SIRT1 (silent mating type information regulation 2 homolog). In view of the role of SIRT1 in acute and chronic renal diseases, we decided to study the effects of RSV-poor red wines on the expression of SIRT1 and HIF-2α (hypoxia-inducible factor 2α) to be compared with a nanomolar concentration of RSV or malvidin in proximal tubular cells of human kidneys (PTEC). Survival signaling systems activation (extracellular signal-regulated kinases, ERK and AMP-activated protein kinase, AMPK) was also investigated in PTEC incubated with wines. PTEC cells were incubated in the presence of RSV-poor wines diluted 1:1,000 for 30′, 90′, 120′ and 24 h. Expression of SIRT1 and HIF-2α, and activation of ERK and AMPK were analyzed by Western Blot. The data obtained show that wine modulates the expression of anti-aging molecular systems even when RSV is present in very small amounts.
Nephrology Dialysis Transplantation, 2014
Background. Endothelial progenitor cells (EPCs) are known to induce tissue repair by paracrine me... more Background. Endothelial progenitor cells (EPCs) are known to induce tissue repair by paracrine mechanisms including the release of growth factors and extracellular vesicles (EVs), nanoparticles able to carry proteins and genetic information to target cells. The aim of this study was to evaluate whether EVs derived from EPCs may protect from complement-mediated mesangial injury in experimental anti-Thy1.1 glomerulonephritis. Methods. EVs were isolated by serial ultracentrifugation from supernatants of cultured human EPCs and characterized for their protein and RNA content. In vivo, EVs were injected i.v. in the experimental rat model of mesangiolytic anti-Thy1.1 glomerulonephritis evaluating renal function, proteinuria, complement activity and histological lesions. In vitro, the biological effects of EPC-derived EVs were studied in cultured rat mesangial cells incubated with anti-Thy1.1 antibody and rat or human serum as complement source. Results. After i.v. injection in Thy1.1-treated rats, EVs localized within injured glomeruli and inhibited mesangial cell activation, leucocyte infiltration and apoptosis, decreased proteinuria, increased serum complement haemolytic activity (CH50) and ameliorated renal function. EV treatment decreased intraglomerular deposition of the membrane attack complex (MAC or C5b-9) and expression of smooth muscle cell actin and preserved the endothelial antigen RECA-1 and the podocyte marker synaptopodin. The protective effect of EVs was significantly reduced by pre-treatment with a high dose of RNase (1 U/mL), suggesting a key role for EV-carried RNAs in these mechanisms. Indeed, EPC-derived EVs contained different mRNAs coding for several anti-apoptotic molecules and for the complement inhibitors Factor H, CD55 and CD59 and the related proteins. The in vitro experiments aimed to investigate the mechanisms of EV protection indicated that EVs transferred to mesangial cell mRNAs coding for Factor H, CD55 and CD59 and inhibited anti-Thy1.1 antibody/complement-induced apoptosis and C5b-9/C3 mesangial cell deposition. Conclusions. EVs derived from EPCs exert a protective effect in Thy1.1 glomerulonephritis by inhibition of antibody-and complement-mediated injury of mesangial cells.
Micron (Oxford, England : 1993), 2014
In recent years, human dental pulp stromal cells (DPSCs) have received growing attention due to t... more In recent years, human dental pulp stromal cells (DPSCs) have received growing attention due to their characteristics in common with other mesenchymal stem cells, in addition to the ease with which they can be harvested. In this study, we demonstrated that the isolation of DPSCs from third molar teeth of healthy individuals allowed the recovery of dental mesenchymal stem cells that showed self-renewal and multipotent differentiation capability. DPSCs resulted positive for CD73, CD90, CD105, STRO-1, negative for CD34, CD45, CD14 and were able to differentiate into osteogenic and chondrogenic cells. We also assayed the angiogenic potential of DPSCs, their capillary tube-like formation was assessed using an in vitro angiogenesis assay and the uptake of acetylated low-density lipoprotein was measured as a marker of endothelial function. Based on these results, DPSCs were capable of differentiating into cells with phenotypic and functional features of endothelial cells. Furthermore, this...
Journal of Agricultural and Food Chemistry, 2005
Ochratoxin A (OTA), is a nephrotoxic mycotoxin present in wine, which is nephrotoxic in humans. O... more Ochratoxin A (OTA), is a nephrotoxic mycotoxin present in wine, which is nephrotoxic in humans. Our working hypothesis is that natural substances in wine may counteract OTA toxicity. Thirty-six rats were randomized to OTA dissolved in saline, red wine, or 13.5% ethanol or to OTA-free wine, ethanol, or saline. OTA (289 µg/kg of body weight/48 h) was administered by gastric gavage for 2 weeks. Serum creatinine, tubular enzymuria, renal lipohydroperoxides (LOOH), reduced (GSH) and oxidized (GSSG) glutathione, and renal superoxide dismutase activity (SOD) were determined in renal tissue. OTA alone produced significant increases in renal lipoperoxides and significant decreases in SOD and GSH/GSSG ratio. In red wine or ethanol, OTA was less nephrotoxic, reducing oxidative damage as revealed by LOOH. In OTA-wine and OTA-ethanol groups, SOD activity was higher than in the OTA-treated one, suggesting that both ethanol and nonalcoholic fractions may preserve antioxidant reserve. GSH/GSSG ratio was significantly preserved only in the OTA-wine group and not in OTA-ethanol. Red wine may exert a protective effect against OTA nephrotoxicity by limiting oxidative damage. The ostensible protection afforded by ethanol deserves further investigation.
Journal of Affective Disorders, 2008
Background: Brain-derived neurotrophic factor (BDNF) has been hypothesized to be involved in the ... more Background: Brain-derived neurotrophic factor (BDNF) has been hypothesized to be involved in the neurobiology of major depression. The aim of this study was to assess the possible relationships between depressive symptoms and serum and/or plasma BDNF levels during 1 year of antidepressant treatment. Methods: Plasma and serum BDNF levels were assayed in 15 drug-free depressed patients and in 15 healthy control subjects at baseline and the 1st, 3rd, 6th and 12th month of antidepressant treatment. Results: At baseline, patients' serum and plasma BDNF levels were significantly lower (p b .001 and p = .004, respectively) than those found in healthy control subjects. However, while from the 1st month of treatment patients' plasma BDNF levels did not differ significantly from those observed in healthy control subjects, serum BDNF levels in patients remained significantly lower at all times. Limitations: The main limitations of the current study are represented by the small sample size and the high discontinuation rate. Conclusions: Untreated depressed patients showed reduced baseline serum and plasma BDNF levels, as compared with control subjects. The clinical improvement paralleled the normalization of plasma BDNF after 1 month of treatment, while, at every assessment time, patients' serum BDNF levels were lower than those of control subjects. This would suggest that serum BDNF might represent a non-specific trait marker of depression.