ANTONIO CARLOS SEGURO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais, Hospital das Clínicas, Faculdade de Medicina - Líder
101 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 101
- Cathelicidin protects mice from Rhabdomyolysis-induced Acute Kidney Injury(2021) SILVA, Beatriz Helena Cermaria Soares da; ARIGA, Suely Kubo; BARBEIRO, Hermes Vieira; VOLPINI, Rildo Aparecido; BARBEIRO, Denise Frediani; SEGURO, Antonio Carlos; SILVA, Fabiano Pinheiro daBackground: Cathelicidins are ancient and well-conserved antimicrobial peptides (AMPs) with intriguing immunomodulatory properties in both infectious and non-infectious inflammatory diseases. In addition to direct antimicrobial activity, cathelicidins also participate in several signaling pathways inducing both pro-inflammatory and anti-inflammatory effects. Acute kidney injury (AKI) is common in critically ill patients and is associated with high mortality and morbidity. Rhabdomyolysis is a major trigger of AKI. Objectives: Here, we investigated the role of cathelicidins in non-infectious Acute kidney Injury (AKI). Method: Using an experimental model of rhabdomyolysis, we induced AKI in wild-type and cathelicidin-related AMP knockout (CRAMP(-/-)) mice. Results: We previously demonstrated that CRAMP(-/-) mice, as opposed wild-type mice, are protected from AKI during sepsis induced by cecal ligation and puncture. Conversely, in the current study, we show that CRAMP(-/-) mice are more susceptible to the rhabdomyolysis model of AKI. A more in-depth investigation of wild-type and CRAMP(-/-) mice revealed important differences in the levels of several inflammatory mediators. Conclusion: Cathelicidins can induce a varied and even opposing repertoire of immune-inflammatory responses depending on the subjacent disease and the cellular context.
- Ecstasy induces reactive oxygen species, kidney water absorption and rhabdomyolysis in normal rats. Effect of N-acetylcysteine and Allopurinol in oxidative stress and muscle fiber damage(2018) BRAGANCA, Ana C. de; MOREAU, Regina L. M.; BRITO, Thales de; SHIMIZU, Maria H. M.; CANALE, Daniele; JESUS, Denise A. de; SILVA, Ana M. G.; GOIS, Pedro H.; SEGURO, Antonio C.; MAGALDI, Antonio J.
bookPart Rins e envelhecimento(2015) LO, Simone Chinwa; SEGURO, Antonio Carlos; ZATZ, Roberto- Vitamin D Deficiency Aggravates Chronic Kidney Disease Progression after Ischemic Acute Kidney Injury(2014) GONCALVES, Janaina Garcia; BRAGANCA, Ana Carolina de; CANALE, Daniele; SHIMIZU, Maria Heloisa Massola; SANCHES, Talita Rojas; MOYSES, Rosa Maria Affonso; ANDRADE, Lucia; SEGURO, Antonio Carlos; VOLPINI, Rildo AparecidoBackground: Despite a significant improvement in the management of chronic kidney disease (CKD), its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-beta 1 (TGF-beta 1). Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD). Methods: Rats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI); and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-beta, and vitamin D receptor (VDR); gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages), type IV collagen, fibronectin, vimentin, and alpha-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area. Results: IRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and alpha-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy), increased expression of TGF-beta 1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals. Conclusion: Through inflammatory pathways and involvement of TGF-beta 1 growth factor, VDD could be considered as an aggravating factor for tubulointerstitial damage and fibrosis progression following acute kidney injury induced by ischemia/reperfusion.
bookPart Ácido úrico e rim(2014) GOIS, Pedro Henrique França; LUCHI, Weverton Machado; SEGURO, Antonio Carlos- Vitamin D Deficiency Aggravates the Renal Features of Moderate Chronic Kidney Disease in 5/6 Nephrectomized Rats(2018) BRAGANCA, Ana Carolina de; CANALE, Daniele; GONCALVES, Janaina Garcia; SHIMIZU, Maria Heloisa Massola; SEGURO, Antonio Carlos; VOLPINI, Rildo AparecidoThe pathogenesis of chronic kidney disease (CKD) involves a very complex interaction between hemodynamic and inflammatory processes, leading to glomerular/vascular sclerosis, and fibrosis formation with subsequent evolution to end-stage of renal disease. Despite efforts to minimize the progression of CKD, its incidence and prevalence continue to increase. Besides cardiovascular diseases and infections, several studies demonstrate that vitamin D status could be considered as a non-traditional risk factor for the progression of CKD. Therefore, we investigated the effects of vitamin D deficiency (VDD) in the course of moderate CKD in 5/6 nephrectomized rats (Nx). Adult male Wistar rats underwent Sham surgery or Nx and were subdivided into the following four groups: Sham, receiving standard diet (Sham); Sham VDD, receiving vitamin D-free diet (VDD); Nx, receiving standard diet (Nx); and VDD+Nx, receiving vitamin D-free diet (VDD+Nx). Sham or Nx surgeries were performed 30 days after standard or vitamin D-free diets administration. After validation of vitamin D depletion, we considered only Nx and VDD+Nx groups for the following studies. Sixty days after surgeries, VDD+Nx rats exhibited hypertension, a greater decline in renal function and plasma FGF-23 levels, renal hypertrophy, as well as higher plasma levels of PTH and aldosterone. In addition, those animals presented more significant chronic tubulointerstitial changes (cortical interstitial expansion/inflammation/fibrosis), higher expression of collagen IV, fibronectin and alpha-smooth muscle actin, and lower expressions of JG12 and M2 macrophages. Also, VDD+Nx rats had greater infiltration of inflammatory cells (M1 macrophages and T-cells). Such changes were accompanied by higher expression of TGF-beta 1 and angiotensinogen and decreased expression of VDR and Klotho protein. Our observations indicate that vitamin D deficiency impairs the renal function and worsens the renovascular and morphological changes, aggravating the features of moderate CKD in 5/6 nephrectomized rats.
- Vitamin D deficiency aggravates ischemic acute kidney injury in rats(2015) BRAGANCA, Ana Carolina de; VOLPINI, Rildo A.; CANALE, Daniele; GONCALVES, Janaina G.; SHIMIZU, Maria Heloisa M.; SANCHES, Talita R.; SEGURO, Antonio C.; ANDRADE, LuciaVitamin D deficiency (VDD) increases the risk of death in hospitalized patients. Renal ischemia/reperfusion injury (IRI) induces acute kidney injury (AKI), which activates cell cycle inhibitors, including p21, a cyclindependent kinase inhibitor and genomic target of 25-hydroxyvitamin D, which is in turn a potent immunomodulator with antiproliferative effects. In this study, we assess the impact of VDD in renal IRI. Wistar rats were divided into groups, each evaluated for 30 days: control (receiving a standard diet); VDD (receiving a vitamin D-free diet); IRI (receiving a standard diet and subjected to 45-min bilateral renal ischemia on day 28); and VDD + IRI (receiving a vitamin D-free diet and subjected to 45-min bilateral renal ischemia on day 28). At 48 h after IRI, animals were euthanized; blood, urine, and kidney tissue samples were collected. Compared with IRI rats, VDD + IRI rats showed a more severe decrease in glomerular filtration rate, greater urinary protein excretion, a higher kidney/body weight ratio and lower renal aquaporin 2 expression, as well as greater morphological damage, characterized by increased interstitial area and tubular necrosis. Our results suggest that the severity of tubular damage in IRI may be associated with downregulation of vitamin D receptors and p21. VDD increases renal inflammation, cell proliferation and cell injury in ischemic AKI.
- Vitamin D Deficiency in Chronic Kidney Disease: Recent Evidence and Controversies(2018) GOIS, Pedro Henrique Franca; WOLLEY, Martin; RANGANATHAN, Dwarakanathan; SEGURO, Antonio CarlosVitamin D (VD) is a pro-hormone essential for life in higher animals. It is present in few types of foods and is produced endogenously in the skin by a photochemical reaction. The final step of VD activation occurs in the kidneys involving a second hydroxylation reaction to generate the biologically active metabolite 1,25(OH)(2)-VD. Extrarenal 1-hydroxylation has also been described to have an important role in autocrine and paracrine signaling. Vitamin D deficiency (VDD) has been in the spotlight as a major public healthcare issue with an estimated prevalence of more than a billion people worldwide. Among individuals with chronic kidney disease (CKD), VDD prevalence has been reported to be as high as 80%. Classically, VD plays a pivotal role in calcium and phosphorus homeostasis. Nevertheless, there is a growing body of evidence supporting the importance of VD in many vital non-skeletal biological processes such as endothelial function, renin-angiotensin-aldosterone system modulation, redox balance and innate and adaptive immunity. In individuals with CKD, VDD has been associated with albuminuria, faster progression of kidney disease and increased all-cause mortality. Recent guidelines support VD supplementation in CKD based on extrapolation from cohorts conducted in the general population. In this review, we discuss new insights on the multifactorial pathophysiology of VDD in CKD as well as how it may negatively modulate different organs and systems. We also critically review the latest evidence and controversies of VD monitoring and supplementation in CKD patients.
conferenceObject IMPACT OF DIFFERENT METHODS OF RENAL REPLACEMENT THERAPY IN WEIL SYNDROME(2015) CLETO, Sergio; MALAQUE, Ceila; RODRIGUES, Camila; SZTAJNBOK, Jaques; SEGURO, Antonio; ANDRADE, LuciaconferenceObject Impaired Kidney Functional In Histidine Dipeptide Depleted Animals. An Exploratory Study With Carns1 Knockout Rats(2022) GONCALVES, Livia S.; NATALI, Jose; SHIMIZU, Maria Heloisa M.; SALES, Lucas P.; SAITO, Tiemi; FERNANDES, Alan L.; GUALANO, Bruno; SEGURO, Antonio Carlos; ARTIOLI, Guilherme G.