Marcos Cenedeze | UNIFESP - Academia.edu (original) (raw)

Papers by Marcos Cenedeze

Research paper thumbnail of TLR-2 and-4 and MyD88 Participate in the Infl ammatory Response Triggered by Acute Renal Injury by Balancing the Immune Response towards a Th2 Profi le through Up Regulation of HO-1

American Journal of Transplantation, 2009

Research paper thumbnail of Cytoprotective Properties of Heme Oxygenase-1 in the Renal Ischemia-Reperfusion Injury in an Obesity and Leptin Deficiency Background

American Journal of Transplantation, 2009

Research paper thumbnail of Th1 and th2 balance and toll-like receptor (TLR2 and 4) activation in renal ischemia and reperfusion injury

American Journal of Transplantation, May 1, 2007

Research paper thumbnail of Hemin modulates hypoxia-induced endoplasmic reticulum stress, through a p38 MAPK-dependent signaling pathway, in renal tubular cells

Frontiers in Immunology, 2018

Ischemia and reperfusion injury (IRI) remains a challenging clinical problem, especially in hospi... more Ischemia and reperfusion injury (IRI) remains a challenging clinical problem, especially in hospitalized patients, and one of the primary aggravators of this insult is inflammation. Endoplasmic reticulum stress (ERS) appears to be an important mediator of this process, leading to the unfolded protein response (UPR), which ultimately aims to alleviate the aggression but could eventually lead to cell death, if ERS is prolonged. Hemin-treatment induces the production of heme oxygenase-1 (HO-1), an enzyme with anti-inflammatory, anti-apoptotic and immunomodulatory properties. Hemin-treatment generates beneficial byproducts, such as carbon monoxide, free iron and biliverdin, that could potentially attenuate ERS. In this study, we explored the role of hemin as a modulatory substance in the protection against ERS-induced lesions prior to both thapsigargin treatment and oxygen and glucose deprivation (OGD) in in vitro systems and in the protection against IRI in an in vivo model of disease. First, we observed that pretreatment with hemin resulted in reduced cell death, decreased expression of inflammatory cytokines, such as TNF-α and IL-6, and reduced ERS, reflected by reductions in BiP, p-eif2α, and chop expression, throughout the evaluated period. Additionally, we observed that lesions triggered by IRI were also modulated by hemin-pretreatment, reflected by reduced renal dysfunction, decreased apoptosis, reduced inflammation and a reduction in ERS markers. Moreover, we verified that the mechanism involved in this protection appears to be mediated by the p38 MAPK pathway, as blockade of this pathway led to the abrogation of the observed protection. We conclude that hemin-pretreatment results in the attenuation of ERS and a reduction in inflammation. Our data further suggests that p38 MAPK could be a valuable therapeutic target for the prevention of renal dysfunction following ischemia.

Research paper thumbnail of Running Title: Kinin receptors in glomerulosclerosis

Research paper thumbnail of Increased lacrimal inflammatory mediators in patients with keratoconus

PubMed, 2021

Purpose: This study aimed to characterize the tear film immunologic profile in keratoconus (KC) p... more Purpose: This study aimed to characterize the tear film immunologic profile in keratoconus (KC) patients compared with healthy individuals (control group) and to investigate the correlation between the tear film immunologic profile and atopy, disease severity, and disease status over time. Methods: The study involved 30 KC patients and 18 healthy individuals. Tear collection was obtained using microcapillary tubes. Tear film levels of fractalkine, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-21, IL-23, interferon-inducible T-cell alpha chemoattractant (ITAC), macrophage inflammatory protein-1 alpha (MIP-1α), MIP-1β, MIP-3α, and tumor necrosis factor (TNF)-α were detected. Keratometric measurements and topographic patterns were used to diagnose and define disease progression. Tear immunologic profiles were compared, emphasizing the presence or absence of ocular allergy. Correlations between the cytokine profile, disease severity, and disease status were also analyzed longitudinally in the KC patients. Results: Lacrimal cytokine concentrations were higher in the KC patients than they were in the controls in 14 of 21 cytokines analyzed. IL-6 was the most relevant cytokine found in KC patients, especially when associated with ocular allergy. There was no correlation between KC progression and the level of inflammatory cytokines when analyzed longitudinally. KC severity correlated with IL-6 concentration, where the more severe KC presented a higher IL-6 concentration in tears. Conclusions: Inflammatory activity seems to be involved in the pathogenesis of KC. Out of 21 cytokines, 14 were more concentrated in the tears of KC patients than healthy subjects. IL-6 was significantly higher in KC patients' tears and was related to disease severity. Disease progression did not correlate with cytokine levels when analyzed longitudinally.

Research paper thumbnail of Low-Level Laser Therapy Decreases Renal Interstitial Fibrosis

Photomedicine and Laser Surgery, Dec 1, 2012

Objective: the purpose of this study was to investigate the effect of low-level laser therapy (LL... more Objective: the purpose of this study was to investigate the effect of low-level laser therapy (LLLT) on chronic kidney disease (CKD) in a model of unilateral ureteral obstruction (UUO). Background data: Regardless of the etiology, CKD involves progressive widespread tissue fibrosis, tubular atrophy, and loss of kidney function. This process also occurs in kidney allograft. At present, effective therapies for this condition are lacking. We investigated the effects of LLLT on the interstitial fibrosis that occurs after experimental UUO in rats. Methods: The occluded kidney of half of the 32 Wistar rats that underwent UUO received a single intraoperative dose of LLLT (AlGaAs laser, 780 nm, 22.5 J/cm 2 , 30 mW, 0.75 W/cm 2 , 30 sec on each of nine points). After 14 days, renal fibrosis was assessed by Sirius red staining under polarized light. Immunohistochemical analyses quantitated the renal tissue cells that expressed fibroblast (FSP-1) and myofibroblast (a-SMA) markers. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the mRNA expression of interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1), transforming growth factor (TGF)-b1 and Smad3. Results: The UUO and LLLT animals had less fibrosis than the UUO animals, as well having decreased expression inflammatory and pro-fibrotic markers. Conclusions: For the first time, we showed that LLLT had a protective effect regarding renal interstitial fibrosis. It is conceivable that by attenuating inflammation, LLLT can prevent tubular activation and transdifferentiation, which are the two processes that mainly drive the renal fibrosis of the UUO model.

Research paper thumbnail of Abstract P256: Higher Angiotensin Converting Enzymes Activities Are Observed In Covid-19 Positive Volunteers

Hypertension, Sep 1, 2022

Research paper thumbnail of The blockade of cyclooxygenases pathway halts the fibrosis after ischernic renal failure

Research paper thumbnail of Role of CD4+CD25+T cells in renal ischemia and reperfusion injury

American Journal of Transplantation, 2006

Research paper thumbnail of A macrophage molecular signature in vascular acute renal allograft rejection

Research paper thumbnail of Expressão De Moléculas Imunorreguladoras Em Rins Não-Funcionantes Com Rejeição Aguda

Brazilian Journal of Transplantation, 2008

Introdução: Tim-3 é uma proteína de membrana com função inibitória, presente em linfócitos Th1. S... more Introdução: Tim-3 é uma proteína de membrana com função inibitória, presente em linfócitos Th1. Seu ligante recentemente identificado, a galectina-9, é expresso em alguns subtipos de linfócitos, e também pode ser induzido por citocinas inflamatórias em células endoteliais e fibroblastos. Juntamente com as células T CD4+CD25+, essas moléculas exercem uma função reguladora da resposta imune. O fator de transcrição FOXP3 está relacionado aos linfócitos T reguladores CD4+CD25+. Objetivo: Avaliar a presença de moléculas relacionadas à resposta imune reguladora intra-enxerto renal durante episódio de rejeição. Material e Métodos: Os níveis de RNA mensageiro para moléculas representativas da resposta imune reguladora (Tim-3, galectina-9 e FOXP3) e da resposta imune citotóxica (perforina, granzima B e interferon-γ) foram quantificados pelo método de reação em cadeia da polimerase em 24 amostras de produtos de enxertectomia, com os seguintes diagnósticos: rejeição aguda não-vascular (n=5), rejeição aguda vascular (n=14) e perda de causa não-imune (n=5, como controle). Resultados: A diferença encontrada entre as medianas dos grupos controle e de rejeição aguda vascular foi estatisticamente significante para todas as moléculas avaliadas: p=0,

Research paper thumbnail of Non-invasive diagnosis of B cell infiltration in renal allografts with acute rejection and chronic nephropathy by detection of CD20 and blimp-1 in urine

American Journal of Transplantation, May 1, 2007

Research paper thumbnail of TH1/TH2 pattern of renal tissues in acute and chronic animal models treated with mesenchymal stem cells

Brazilian Journal of Transplantation, 2007

Mesenchymal stem cell (MSC) therapy is a promising new therapy for kidney diseases. Many authors ... more Mesenchymal stem cell (MSC) therapy is a promising new therapy for kidney diseases. Many authors have been demonstrated that the MSC treatment leads to N improvement of the renal function in acute damaged models. However, the way it works still remains elusive. Purpose: To evaluate whether the renal protection provided by MSC administration seen in acute and chronic renal remnant damaged models involves modulation of the inflammation. Methods: MSC were attained from bone marrow of male Wistar rats. Female Wistar were subjected to ischemia-reperfusion damage by clamping renal pedicles for 1 hour. After a 6h reperfusion, 2.105 MSC were administrated i.v. in the chronic model. The nephrectomy models 5/6 were treated with 1.106 MSC administered i.v. after two weeks. Results: After a 24h reperfusion, MSC-treated animals presented a significant improvement of the renal function associated to decreased levels of IL-1β, IL-6 and TNF-α gene expression. Interestingly, the IL-4 mRNA expression i...

Research paper thumbnail of Gut Microbiota and Intestinal Epithelial Myd88 Signaling Are Crucial for Renal Injury in UUO Mice

Frontiers in Immunology, 2020

Increasing evidence shows the essential participation of gut microbiota in human health and disea... more Increasing evidence shows the essential participation of gut microbiota in human health and diseases by shaping local and systemic immunity. Despite an accumulating body of studies showing that chronic kidney disease (CKD) is closely associated with disturbances in the composition of gut microbiota, it remains unclear the importance of gut microbiota in the onset and development of CKD. For the purpose of untangling the role of gut microbiota in CKD, gut microbiota was depleted with a pool of broad-spectrum antibiotics in mice submitted to unilateral ureteral obstruction (UUO). Depletion of gut microbiota significantly decreased levels of proinflammatory cytokines and fibrosis markers, attenuating renal injury. Additionally, to study whether the pathogenic role of gut microbiota is dependent of microbial-host crosstalk, we generated mice lacking Myd88 (myeloid differentiation primary response gene 8) expression in intestinal epithelial cells (IECs) and performed UUO. The absence of ...

Research paper thumbnail of NF-κB System Is Chronically Activated and Promotes Glomerular Injury in Experimental Type 1 Diabetic Kidney Disease

Frontiers in Physiology, 2020

High glucose concentration can activate TLR4 and NF-κB, triggering the production of proinflammat... more High glucose concentration can activate TLR4 and NF-κB, triggering the production of proinflammatory mediators. We investigated whether the NF-κB pathway is involved in the pathogenesis and progression of experimental diabetic kidney disease (DKD) in a model of long-term type 1 diabetes mellitus (DM). Adult male Munich-Wistar rats underwent DM by a single streptozotocin injection, and were kept moderately hyperglycemic by daily insulin injections. After 12 months, two subgroups-progressors and non-progressors-could be formed based on the degree of glomerulosclerosis. Only progressors exhibited renal TLR4, NF-κB and IL-6 activation. This scenario was already present in rats with short-term DM (2 months), at a time when no overt glomerulosclerosis can be detected. Chronic treatment with the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), prevented activation of renal TLR4, NF-κB or IL-6, without interfering with blood glucose. PDTC prevented the development of glomerular injury/inflammation and oxidative stress in DM rats. In addition, the NF-κB p65 component was detected in sclerotic glomeruli and inflamed interstitial areas in biopsy material from patients with type 1 DM. These observations indicate that the renal NF-κB pathway plays a key role in the development and progression of experimental DKD, and can become an important therapeutic target in the quest to prevent the progression of human DKD.

Research paper thumbnail of l-Arginine supplementation blunts resistance exercise improvement in rats with chronic kidney disease

Research paper thumbnail of Correction: Bradykinin B1 Receptor Antagonism Is Beneficial in Renal Ischemia-Reperfusion Injury

Research paper thumbnail of P-608

Fertility and Sterility, 2006

Research paper thumbnail of High Serum Levels of Soluble Fas (sFas) in Ckd Patients: Effects of Renal Clearance, Reabsorption and Synthesis

The International Journal of Artificial Organs, 2008

PurposeIncreased serum concentrations of soluble Fas (sFas) have been reported in patients with c... more PurposeIncreased serum concentrations of soluble Fas (sFas) have been reported in patients with chronic kidney disease (CKD). However, little is known about the renal clearance of sFas, whether sFas is reabsorbed in the renal tubules, or the behavior of sFas synthesis in CKD.Materials and MethodsWe studied 69 patients with CKD (60±15 years old, creatinine clearance 37+19 ml/min/1.73 m2) and 14 healthy subjects (61±17 years, creatinine clearance 79±24 ml/min/1.73 m2). ELISA was used to measure the levels of sFas (pg/mL) and retinol binding protein (RBP - mg/L). RT-PCR was used to quantify sFasmRNA of leukocytes.ResultsSerum sFas levels were significantly higher in patients with CKD (2781±1214 vs. 2196±773, p=0.02). The concentrations of sFas in 24-hour urine samples (23±27 vs. 40±17, p=0.006) and sFas Clearance (0.019±0.022 vs. 0.036±0.020, p=0.01) were significantly lower in patients with CKD. sFas clearance correlated with creatinine clearance (r=0.25, p=0.02). Urine concentrations...

Research paper thumbnail of TLR-2 and-4 and MyD88 Participate in the Infl ammatory Response Triggered by Acute Renal Injury by Balancing the Immune Response towards a Th2 Profi le through Up Regulation of HO-1

American Journal of Transplantation, 2009

Research paper thumbnail of Cytoprotective Properties of Heme Oxygenase-1 in the Renal Ischemia-Reperfusion Injury in an Obesity and Leptin Deficiency Background

American Journal of Transplantation, 2009

Research paper thumbnail of Th1 and th2 balance and toll-like receptor (TLR2 and 4) activation in renal ischemia and reperfusion injury

American Journal of Transplantation, May 1, 2007

Research paper thumbnail of Hemin modulates hypoxia-induced endoplasmic reticulum stress, through a p38 MAPK-dependent signaling pathway, in renal tubular cells

Frontiers in Immunology, 2018

Ischemia and reperfusion injury (IRI) remains a challenging clinical problem, especially in hospi... more Ischemia and reperfusion injury (IRI) remains a challenging clinical problem, especially in hospitalized patients, and one of the primary aggravators of this insult is inflammation. Endoplasmic reticulum stress (ERS) appears to be an important mediator of this process, leading to the unfolded protein response (UPR), which ultimately aims to alleviate the aggression but could eventually lead to cell death, if ERS is prolonged. Hemin-treatment induces the production of heme oxygenase-1 (HO-1), an enzyme with anti-inflammatory, anti-apoptotic and immunomodulatory properties. Hemin-treatment generates beneficial byproducts, such as carbon monoxide, free iron and biliverdin, that could potentially attenuate ERS. In this study, we explored the role of hemin as a modulatory substance in the protection against ERS-induced lesions prior to both thapsigargin treatment and oxygen and glucose deprivation (OGD) in in vitro systems and in the protection against IRI in an in vivo model of disease. First, we observed that pretreatment with hemin resulted in reduced cell death, decreased expression of inflammatory cytokines, such as TNF-α and IL-6, and reduced ERS, reflected by reductions in BiP, p-eif2α, and chop expression, throughout the evaluated period. Additionally, we observed that lesions triggered by IRI were also modulated by hemin-pretreatment, reflected by reduced renal dysfunction, decreased apoptosis, reduced inflammation and a reduction in ERS markers. Moreover, we verified that the mechanism involved in this protection appears to be mediated by the p38 MAPK pathway, as blockade of this pathway led to the abrogation of the observed protection. We conclude that hemin-pretreatment results in the attenuation of ERS and a reduction in inflammation. Our data further suggests that p38 MAPK could be a valuable therapeutic target for the prevention of renal dysfunction following ischemia.

Research paper thumbnail of Running Title: Kinin receptors in glomerulosclerosis

Research paper thumbnail of Increased lacrimal inflammatory mediators in patients with keratoconus

PubMed, 2021

Purpose: This study aimed to characterize the tear film immunologic profile in keratoconus (KC) p... more Purpose: This study aimed to characterize the tear film immunologic profile in keratoconus (KC) patients compared with healthy individuals (control group) and to investigate the correlation between the tear film immunologic profile and atopy, disease severity, and disease status over time. Methods: The study involved 30 KC patients and 18 healthy individuals. Tear collection was obtained using microcapillary tubes. Tear film levels of fractalkine, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-21, IL-23, interferon-inducible T-cell alpha chemoattractant (ITAC), macrophage inflammatory protein-1 alpha (MIP-1α), MIP-1β, MIP-3α, and tumor necrosis factor (TNF)-α were detected. Keratometric measurements and topographic patterns were used to diagnose and define disease progression. Tear immunologic profiles were compared, emphasizing the presence or absence of ocular allergy. Correlations between the cytokine profile, disease severity, and disease status were also analyzed longitudinally in the KC patients. Results: Lacrimal cytokine concentrations were higher in the KC patients than they were in the controls in 14 of 21 cytokines analyzed. IL-6 was the most relevant cytokine found in KC patients, especially when associated with ocular allergy. There was no correlation between KC progression and the level of inflammatory cytokines when analyzed longitudinally. KC severity correlated with IL-6 concentration, where the more severe KC presented a higher IL-6 concentration in tears. Conclusions: Inflammatory activity seems to be involved in the pathogenesis of KC. Out of 21 cytokines, 14 were more concentrated in the tears of KC patients than healthy subjects. IL-6 was significantly higher in KC patients' tears and was related to disease severity. Disease progression did not correlate with cytokine levels when analyzed longitudinally.

Research paper thumbnail of Low-Level Laser Therapy Decreases Renal Interstitial Fibrosis

Photomedicine and Laser Surgery, Dec 1, 2012

Objective: the purpose of this study was to investigate the effect of low-level laser therapy (LL... more Objective: the purpose of this study was to investigate the effect of low-level laser therapy (LLLT) on chronic kidney disease (CKD) in a model of unilateral ureteral obstruction (UUO). Background data: Regardless of the etiology, CKD involves progressive widespread tissue fibrosis, tubular atrophy, and loss of kidney function. This process also occurs in kidney allograft. At present, effective therapies for this condition are lacking. We investigated the effects of LLLT on the interstitial fibrosis that occurs after experimental UUO in rats. Methods: The occluded kidney of half of the 32 Wistar rats that underwent UUO received a single intraoperative dose of LLLT (AlGaAs laser, 780 nm, 22.5 J/cm 2 , 30 mW, 0.75 W/cm 2 , 30 sec on each of nine points). After 14 days, renal fibrosis was assessed by Sirius red staining under polarized light. Immunohistochemical analyses quantitated the renal tissue cells that expressed fibroblast (FSP-1) and myofibroblast (a-SMA) markers. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the mRNA expression of interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1), transforming growth factor (TGF)-b1 and Smad3. Results: The UUO and LLLT animals had less fibrosis than the UUO animals, as well having decreased expression inflammatory and pro-fibrotic markers. Conclusions: For the first time, we showed that LLLT had a protective effect regarding renal interstitial fibrosis. It is conceivable that by attenuating inflammation, LLLT can prevent tubular activation and transdifferentiation, which are the two processes that mainly drive the renal fibrosis of the UUO model.

Research paper thumbnail of Abstract P256: Higher Angiotensin Converting Enzymes Activities Are Observed In Covid-19 Positive Volunteers

Hypertension, Sep 1, 2022

Research paper thumbnail of The blockade of cyclooxygenases pathway halts the fibrosis after ischernic renal failure

Research paper thumbnail of Role of CD4+CD25+T cells in renal ischemia and reperfusion injury

American Journal of Transplantation, 2006

Research paper thumbnail of A macrophage molecular signature in vascular acute renal allograft rejection

Research paper thumbnail of Expressão De Moléculas Imunorreguladoras Em Rins Não-Funcionantes Com Rejeição Aguda

Brazilian Journal of Transplantation, 2008

Introdução: Tim-3 é uma proteína de membrana com função inibitória, presente em linfócitos Th1. S... more Introdução: Tim-3 é uma proteína de membrana com função inibitória, presente em linfócitos Th1. Seu ligante recentemente identificado, a galectina-9, é expresso em alguns subtipos de linfócitos, e também pode ser induzido por citocinas inflamatórias em células endoteliais e fibroblastos. Juntamente com as células T CD4+CD25+, essas moléculas exercem uma função reguladora da resposta imune. O fator de transcrição FOXP3 está relacionado aos linfócitos T reguladores CD4+CD25+. Objetivo: Avaliar a presença de moléculas relacionadas à resposta imune reguladora intra-enxerto renal durante episódio de rejeição. Material e Métodos: Os níveis de RNA mensageiro para moléculas representativas da resposta imune reguladora (Tim-3, galectina-9 e FOXP3) e da resposta imune citotóxica (perforina, granzima B e interferon-γ) foram quantificados pelo método de reação em cadeia da polimerase em 24 amostras de produtos de enxertectomia, com os seguintes diagnósticos: rejeição aguda não-vascular (n=5), rejeição aguda vascular (n=14) e perda de causa não-imune (n=5, como controle). Resultados: A diferença encontrada entre as medianas dos grupos controle e de rejeição aguda vascular foi estatisticamente significante para todas as moléculas avaliadas: p=0,

Research paper thumbnail of Non-invasive diagnosis of B cell infiltration in renal allografts with acute rejection and chronic nephropathy by detection of CD20 and blimp-1 in urine

American Journal of Transplantation, May 1, 2007

Research paper thumbnail of TH1/TH2 pattern of renal tissues in acute and chronic animal models treated with mesenchymal stem cells

Brazilian Journal of Transplantation, 2007

Mesenchymal stem cell (MSC) therapy is a promising new therapy for kidney diseases. Many authors ... more Mesenchymal stem cell (MSC) therapy is a promising new therapy for kidney diseases. Many authors have been demonstrated that the MSC treatment leads to N improvement of the renal function in acute damaged models. However, the way it works still remains elusive. Purpose: To evaluate whether the renal protection provided by MSC administration seen in acute and chronic renal remnant damaged models involves modulation of the inflammation. Methods: MSC were attained from bone marrow of male Wistar rats. Female Wistar were subjected to ischemia-reperfusion damage by clamping renal pedicles for 1 hour. After a 6h reperfusion, 2.105 MSC were administrated i.v. in the chronic model. The nephrectomy models 5/6 were treated with 1.106 MSC administered i.v. after two weeks. Results: After a 24h reperfusion, MSC-treated animals presented a significant improvement of the renal function associated to decreased levels of IL-1β, IL-6 and TNF-α gene expression. Interestingly, the IL-4 mRNA expression i...

Research paper thumbnail of Gut Microbiota and Intestinal Epithelial Myd88 Signaling Are Crucial for Renal Injury in UUO Mice

Frontiers in Immunology, 2020

Increasing evidence shows the essential participation of gut microbiota in human health and disea... more Increasing evidence shows the essential participation of gut microbiota in human health and diseases by shaping local and systemic immunity. Despite an accumulating body of studies showing that chronic kidney disease (CKD) is closely associated with disturbances in the composition of gut microbiota, it remains unclear the importance of gut microbiota in the onset and development of CKD. For the purpose of untangling the role of gut microbiota in CKD, gut microbiota was depleted with a pool of broad-spectrum antibiotics in mice submitted to unilateral ureteral obstruction (UUO). Depletion of gut microbiota significantly decreased levels of proinflammatory cytokines and fibrosis markers, attenuating renal injury. Additionally, to study whether the pathogenic role of gut microbiota is dependent of microbial-host crosstalk, we generated mice lacking Myd88 (myeloid differentiation primary response gene 8) expression in intestinal epithelial cells (IECs) and performed UUO. The absence of ...

Research paper thumbnail of NF-κB System Is Chronically Activated and Promotes Glomerular Injury in Experimental Type 1 Diabetic Kidney Disease

Frontiers in Physiology, 2020

High glucose concentration can activate TLR4 and NF-κB, triggering the production of proinflammat... more High glucose concentration can activate TLR4 and NF-κB, triggering the production of proinflammatory mediators. We investigated whether the NF-κB pathway is involved in the pathogenesis and progression of experimental diabetic kidney disease (DKD) in a model of long-term type 1 diabetes mellitus (DM). Adult male Munich-Wistar rats underwent DM by a single streptozotocin injection, and were kept moderately hyperglycemic by daily insulin injections. After 12 months, two subgroups-progressors and non-progressors-could be formed based on the degree of glomerulosclerosis. Only progressors exhibited renal TLR4, NF-κB and IL-6 activation. This scenario was already present in rats with short-term DM (2 months), at a time when no overt glomerulosclerosis can be detected. Chronic treatment with the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), prevented activation of renal TLR4, NF-κB or IL-6, without interfering with blood glucose. PDTC prevented the development of glomerular injury/inflammation and oxidative stress in DM rats. In addition, the NF-κB p65 component was detected in sclerotic glomeruli and inflamed interstitial areas in biopsy material from patients with type 1 DM. These observations indicate that the renal NF-κB pathway plays a key role in the development and progression of experimental DKD, and can become an important therapeutic target in the quest to prevent the progression of human DKD.

Research paper thumbnail of l-Arginine supplementation blunts resistance exercise improvement in rats with chronic kidney disease

Research paper thumbnail of Correction: Bradykinin B1 Receptor Antagonism Is Beneficial in Renal Ischemia-Reperfusion Injury

Research paper thumbnail of P-608

Fertility and Sterility, 2006

Research paper thumbnail of High Serum Levels of Soluble Fas (sFas) in Ckd Patients: Effects of Renal Clearance, Reabsorption and Synthesis

The International Journal of Artificial Organs, 2008

PurposeIncreased serum concentrations of soluble Fas (sFas) have been reported in patients with c... more PurposeIncreased serum concentrations of soluble Fas (sFas) have been reported in patients with chronic kidney disease (CKD). However, little is known about the renal clearance of sFas, whether sFas is reabsorbed in the renal tubules, or the behavior of sFas synthesis in CKD.Materials and MethodsWe studied 69 patients with CKD (60±15 years old, creatinine clearance 37+19 ml/min/1.73 m2) and 14 healthy subjects (61±17 years, creatinine clearance 79±24 ml/min/1.73 m2). ELISA was used to measure the levels of sFas (pg/mL) and retinol binding protein (RBP - mg/L). RT-PCR was used to quantify sFasmRNA of leukocytes.ResultsSerum sFas levels were significantly higher in patients with CKD (2781±1214 vs. 2196±773, p=0.02). The concentrations of sFas in 24-hour urine samples (23±27 vs. 40±17, p=0.006) and sFas Clearance (0.019±0.022 vs. 0.036±0.020, p=0.01) were significantly lower in patients with CKD. sFas clearance correlated with creatinine clearance (r=0.25, p=0.02). Urine concentrations...