TALITA ROJAS CUNHA SANCHES
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais, Hospital das Clínicas, Faculdade de Medicina
LIM/08 - Laboratório de Anestesiologia, Hospital das Clínicas, Faculdade de Medicina
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais, Hospital das Clínicas, Faculdade de Medicina
LIM/08 - Laboratório de Anestesiologia, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- Effects of Continuous Erythropoietin Receptor Activator in Sepsis-Induced Acute Kidney Injury and Multi-Organ Dysfunction(2012) RODRIGUES, Camila E.; SANCHES, Talita R.; VOLPINI, Rildo A.; SHIMIZU, Maria H. M.; KURIKI, Patricia S.; CAMARA, Niels O. S.; SEGURO, Antonio C.; ANDRADE, LuciaBackground: Despite advances in supportive care, sepsis-related mortality remains high, especially in patients with acute kidney injury (AKI). Erythropoietin can protect organs against ischemia and sepsis. This effect has been linked to activation of intracellular survival pathways, although the mechanism remains unclear. Continuous erythropoietin receptor activator (CERA) is an erythropoietin with a unique pharmacologic profile and long half-life. We hypothesized that pretreatment with CERA would be renoprotective in the cecal ligation and puncture (CLP) model of sepsis-induced AKI. Methods: Rats were randomized into three groups: control; CLP; and CLP+CERA (5 mu g/kg body weight, i.p. administered 24 h before CLP). At 24 hours after CLP, we measured creatinine clearance, biochemical variables, and hemodynamic parameters. In kidney tissue, we performed immunoblotting-to quantify expression of the Na-K-2Cl cotransporter (NKCC2), aquaporin 2 (AQP2), Toll-like receptor 4 (TLR4), erythropoietin receptor (EpoR), and nuclear factor kappa B (NF-kappa B)-and immunohistochemical staining for CD68 (macrophage infiltration). Plasma interleukin (IL)-2, IL-1 beta, IL-6, IL-10, interferon gamma, and tumor necrosis factor alpha were measured by multiplex detection. Results: Pretreatment with CERA preserved creatinine clearance and tubular function, as well as the expression of NKCC2 and AQP2. In addition, CERA maintained plasma lactate at normal levels, as well as preserving plasma levels of transaminases and lactate dehydrogenase. Renal expression of TLR4 and NF-kappa B was lower in CLP+CERA rats than in CLP rats (p<0.05 and p<0.01, respectively), as were CD68-positive cell counts (p<0.01), whereas renal EpoR expression was higher (p<0.05). Plasma levels of all measured cytokines were lower in CLP+CERA rats than in CLP rats. Conclusion: CERA protects against sepsis-induced AKI. This protective effect is, in part, attributable to suppression of the inflammatory response.
- Klotho deficiency aggravates sepsis-related multiple organ dysfunction(2019) JORGE, Lecticia B.; COELHO, Fernanda O.; SANCHES, Talita R.; MALHEIROS, Denise M. A. C.; SOUZA, Leandro Ezaquiel de; SANTOS, Fernando dos; LIMA, Larissa de Sa; SCAVONE, Cristoforo; IRIGOYEN, Maria; KURO-O, Makoto; ANDRADE, LuciaSepsis-induced organ failure is characterized by a massive inflammatory response and oxidative stress. Acute kidney injury (AKI) occurs in approximately half of patients in septic shock, and the mortality associated with sepsis-induced AKI is unacceptably high. Klotho is a protein expressed by renal cells and has anti-senescence properties. Klotho has also been shown to protect the kidneys in ischemia-reperfusion injury and to have antioxidant properties. To analyze the role of Klotho in sepsis-related organ dysfunction and AKI, we used a cecal ligation and puncture (CLP) model of sepsis in heterozygous Klotho-haploinsufficient mice and their wild-type littermates (CLP-Kl/+ and CLP-WT mice, respectively). In comparison with the CLP-WT mice, CLP-Kl/+ mice showed lower survival, impaired renal function, impaired hepatic function, greater oxidative stress, upregulation of inflammatory pathways (at the systemic and kidney tissue levels), and increased NF-KB activation. It is noteworthy that CLP-Kl/+ mice also showed lower heart-rate variability, less sympathetic activity, impaired baroreflex sensitivity to sodium nitroprussidc, and a blunted blood pressure response to phenylephrine. We also demonstrated that sepsis creates a state of acute Klotho deficiency. Given that low Klotho expression exacerbates sepsis and multiple organ dysfunction. Klotho might play a protective role in sepsis, especially in elderly individuals in whom Klotho expression is naturally reduced.
- Erythropoietin prevents sepsis-related acute kidney injury in rats by inhibiting NF-kappa B and upregulating endothelial nitric oxide synthase(2012) SOUZA, Ana Carolina C. Pessoa de; VOLPINI, Rildo A.; SHIMIZU, Maria Heloisa; SANCHES, Talita Rojas; CAMARA, Niels Olsen Saraiva; SEMEDO, Patricia; RODRIGUES, Camila Eleuterio; SEGURO, Antonio Carlos; ANDRADE, Luciade Souza ACCP, Volpini RA, Shimizu MH, Sanches TR, Camara NOS, Semedo P, Rodrigues CE, Seguro AC, Andrade L. Erythropoietin prevents sepsis-related acute kidney injury in rats by inhibiting nuclear factor-kappa B and upregulating endothelial nitric oxide synthase. Am J Physiol Renal Physiol 302: F1045-F1054, 2012. First published January 11, 2012; doi:10.1152/ajprenal.00148.2011.-The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks, a mechanism to which NF-kappa B activation is central. Downregulation of endothelial nitric oxide synthase (eNOS) contributes to sepsis-induced endothelial dysfunction. Erythropoietin (EPO) has emerged as a major tissue-protective cytokine in the setting of stress. We investigated the role of EPO in sepsis-related acute kidney injury using a cecal ligation and puncture (CLP) model. Wistar rats were divided into three primary groups: control (sham-operated); CLP; and CLP + EPO. EPO (4,000 IU/kg body wt ip) was administered 24 and 1 h before CLP. Another group of rats received N-nitro-L-arginine methyl ester (L-NAME) simultaneously with EPO administration (CLP + EPO + L-NAME). A fifth group (CLP + EPOtreat) received EPO at 1 and 4 h after CLP. At 48 h postprocedure, CLP + EPO rats presented significantly higher inulin clearance than did CLP and CLP + EPO + L-NAME rats; hematocrit levels, mean arterial pressure, and metabolic balance remained unchanged in the CLP + EPO rats; and inulin clearance was significantly higher in CLP + EPOtreat rats than in CLP rats. At 48 h after CLP, creatinine clearance was significantly higher in the CLP + EPO rats than in the CLP rats. In renal tissue, pre-CLP EPO administration prevented the sepsis-induced increase in macrophage infiltration, as well as preserving eNOS expression, EPO receptor (EpoR) expression, IKK-alpha activation, NF-kappa B activation, and inflammatory cytokine levels, thereby increasing survival. We conclude that this protection, which appears to be dependent on EpoR activation and on eNOS expression, is attributable, in part, to inhibition of the inflammatory response via NF-kappa B downregulation.
- Acute kidney injury in a mouse model of meningococcal disease(2021) KOLBE, Karin R.; SANCHES, Talita R.; FANELLI, Camilla; GARNICA, Margoth R.; CASTRO, Leticia Urbano de; GOOCH, Karen; THOMAS, Stephen; TAYLOR, Stephen; GORRINGE, Andrew; NORONHA, Irene de L.; ANDRADE, LuciaIntroduction Meningococcal disease is associated with high mortality. When acute kidney injury (AKI) occurs in patients with severe meningococcal disease, it is typically attributable to sepsis, although meningococcal disease and lipopolysaccharide release are rarely investigated. Therefore, we evaluated renal tissue in a mouse model of meningococcal disease. Methods Female BALB/c mice were induced to AKI by meningococcal challenge. Markers of renal function were evaluated in infected and control mice. Results In the infected mice, serum concentrations of tumor necrosis factor alpha, interferon gamma, interleukins (IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-12), and granulocyte-macrophage colony-stimulating factor were elevated, as was renal interstitial infiltration with lymphocytes and neutrophils (p < 0.01 for the latter). Histological analysis showed meningococcal microcolonies in the renal interstitium, without acute tubular necrosis. Infected mice also showed elevated renal expression of toll-like receptor 2, toll-like receptor 4, and Tamm-Horsfall protein. The expression of factors in the intrinsic pathway of apoptosis was equal to or lower than that observed in the control mice. Urinary sodium and potassium were also lower in infected mice, probably due to a tubular defect. Conclusion Our findings corroborate those of other studies of AKI in sepsis. To our knowledge, this is the first time that meningococci have been identified in renal interstitium and that the resulting apoptosis and inflammation have been evaluated. However, additional studies are needed in order to elucidate the mechanisms involved.