CLEONICE DA SILVA
Índice h a partir de 2011
4
Projetos de Pesquisa
Unidades Organizacionais
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
Agora exibindo 1 - 2 de 2
- Terlipressin combined with conservative fluid management attenuates hemorrhagic shock-induced acute kidney injury in rats(2022) CASTRO, Leticia Urbano Cardoso; OTSUKI, Denise Aya; SANCHES, Talita Rojas; SOUZA, Felipe Lima; SANTINHO, Mirela Aparecida Rodrigues; SILVA, Cleonice da; NORONHA, Irene de Lourdes; DUARTE-NETO, Amaro Nunes; GOMES, Samirah Abreu; MALBOUISSON, Luiz-Marcelo Sa; ANDRADE, LuciaHemorrhagic shock (HS), a major cause of trauma-related mortality, is mainly treated by crystalloid fluid administration, typically with lactated Ringer's (LR). Despite beneficial hemodynamic effects, such as the restoration of mean arterial pressure (MAP), LR administration has major side effects, including organ damage due to edema. One strategy to avoid such effects is pre-hospitalization intravenous administration of the potent vasoconstrictor terlipressin, which can restore hemodynamic stability/homeostasis and has anti-inflammatory effects. Wistar rats were subjected to HS for 60 min, at a target MAP of 30-40 mmHg, thereafter being allocated to receive LR infusion at 3 times the volume of the blood withdrawn (liberal fluid management); at 2 times the volume (conservative fluid management), plus terlipressin (10 mu g/100 g body weight); and at an equal volume (conservative fluid management), plus terlipressin (10 mu g/100 g body weight). A control group comprised rats not subjected to HS and receiving no fluid resuscitation or treatment. At 15 min after fluid resuscitation/treatment, the blood previously withdrawn was reinfused. At 24 h after HS, MAP was higher among the terlipressin-treated animals. Terlipressin also improved post-HS survival and provided significant improvements in glomerular/tubular function (creatinine clearance), neutrophil gelatinase-associated lipocalin expression, fractional excretion of sodium, aquaporin 2 expression, tubular injury, macrophage infiltration, interleukin 6 levels, interleukin 18 levels, and nuclear factor kappa B expression. In terlipressin-treated animals, there was also significantly higher angiotensin II type 1 receptor expression and normalization of arginine vasopressin 1a receptor expression. Terlipressin associated with conservative fluid management could be a viable therapy for HS-induced acute kidney injury, likely attenuating such injury by modulating the inflammatory response via the arginine vasopressin 1a receptor.
- Thalidomide suppresses inflammation in adenine-induced CKD with uraemia in mice(2013) SANTANA, Alexandre C.; DEGASPARI, Sabrina; CATANOZI, Sergio; DELLE, Humberto; LIMA, Larissa De Sa; SILVA, Cleonice; BLANCO, Paula; SOLEZ, Kim; SCAVONE, Cristoforo; NORONHA, Irene L.Persistent systemic inflammation has been widely recognized in patients with chronic kidney disease (CKD), and is associated with increased risk of morbidity and mortality. Intervention therapies aiming for the blockade of inflammatory cytokines are considered attractive approaches for CKD patients with signs of chronic inflammation. In this context, thalidomide, due to its potent anti-inflammatory and immunomodulatory properties, may represent an alternative strategy of treatment. In the present study, we developed an experimental model of CKD with uraemia in mice, induced by a diet rich in adenine, which causes progressive renal dysfunction, resembling the human uraemic features. Inflammatory parameters were analysed in this model of CKD and the potential beneficial effects of thalidomide as an anti-inflammatory drug was also investigated. C57/BL-6 mice were fed with an adenine-containing diet during a period of 6 weeks. Thirty mice were divided into three groups: Control group (animals receiving normal diet), ADE group (mice receiving adenine-containing diet) and ADE TLD group (CKD mice receiving thalidomide, 30 mg/kg/day, by gavage). Besides biochemical and histopathological changes, local and systemic inflammatory parameters were also analysed, including expression of cytokines interleukin (IL)-1, tumour necrosis factor-, IL-6, IL-4 and IL-10 in kidney samples by real-time RTPCR and quantification of serum levels of cytokines. Finally, the electrophoretic mobility shift assay (EMSA) for NF-B was also examined. Adenine-fed mice developed advanced CKD characterized by a marked increase in serum urea, creatinine, phosphorus and intact parathyroid hormone (iPTH) levels. In addition, histological changes of tubulointerstitial injury, characterized by deposition of crystals in the kidney, accompanied by tubular dilatation, degeneration of proximal tubular epithelium with loss of the brush border, inflammatory cellular infiltration, foreign-body granuloma formation and interstitial fibrosis were also evident. By immunohistochemistry, Mac-2- and -SMA-positive cells were identified in the tubulointerstitial compartment. Treatment with thalidomide significantly reduced serum urea, creatinine, phosphorus and iPTH levels and protected against tubulointerstitial injury. Local and systemic inflammation in the mice model of adenine-induced CKD was confirmed by the findings of significantly high expression of cytokine mRNA levels and NF-B activation in the kidney tissue as well as marked increased serum levels of in?ammatory cytokines. Thalidomide treatment significantly reduced gene expression of these cytokines and the activation of the NF-B in the renal tissue and the circulating levels of cytokines. Dietary adenine caused advanced CKD with uraemia in mice providing a useful experimental model to study molecular and morphological changes associated with this disease. The negative impact of inflammation in this CKD model was overcome by the marked anti-inflammatory effects of thalidomide, promoting renal protection.