ANA CRISTINA BREITHAUPT FALOPPA
Projetos de Pesquisa
Unidades Organizacionais
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- PROTECTIVE EFFECT OF ESTRADIOL ON ACUTE LUNG INFLAMMATION INDUCED BY AN INTESTINAL ISCHEMIC INSULT IS DEPENDENT ON NITRIC OXIDE(2013) BREITHAUPT-FALOPPA, A. C.; FANTOZZI, E. T.; ASSIS-RAMOS, M. M.; VITORETTI, L. B.; COUTO, G. K.; ROSSONI, L. V.; OLIVEIRA-FILHO, R. M.; VARGAFTIG, B. B.; TAVARES-DE-LIMA, W.Introduction: It has been shown that the innate immune system mediates acute lung inflammation triggered by intestinal trauma. Sexual dimorphism modulates the profile of T(H)1 and T(H)2 lymphocytes, and accordingly sex hormones may modulate acute lung inflammation by intestinal ischemia/reperfusion (I/R). Studies indicate that female rats are relatively resistant to organ injury caused by hemorrhagic shock and that the gut of female is more resistant than that of the male to deleterious effects of ischemic injury. At the present study, we investigated the effect of estradiol (E-2) on the lung inflammation after intestinal I/R and its interaction with the nitric oxide (NO) pathway. Methods: Anesthetized female rats submitted or not to 7 days ovariectomy (OVx) were subjected to occlusion of the superior mesenteric artery during 45 min, followed by 2 h of reperfusion. Groups of rats were treated with E2 (17 beta-estradiol, 280 mu g/kg, s.c.) 24 h before ischemia and/or with the nonselective NO synthase inhibitor L-NAME (N5-nitro-L-arginine methyl ester hydrochloride) (5 mg/kg, i.v.). In a parallel set of experiments, the selective NO synthase inhibitor, aminoguanidine (50 mg/kg i.v.), was given 1 h before ischemia. In all groups, lung vascular permeability (LVP) was assessed using the Evans blue dye extravasation method, neutrophil recruitment to the tissues by the standard myeloperoxidase (MPO) method, and endothelial NO synthase (eNOS) protein expression by Western blot. Results: In OVx rats, LVP and MPO were increased after intestinal I/R as compared with intact controls. Estradiol reverted the LVP, but not MPO. Aminoguanidine reduced LVP in OVx rats. The E2 protective effect on LVP was abolished by L-NAME; moreover, an increase in LVP even when compared with OVx rats treated only with L-NAME was observed. In addition, lung eNOS protein expression was reduced in OVx-I/R rats in comparison to intact controls and the E2 inhibited this effect. Conclusions: Estradiol treatment is able to reduce lung inflammation due to intestinal I/R, but with the concomitant blockade of NOS activity, this effect is abolished. Nitric oxide probably reduces the vascular deleterious effects of intestinal I/R, and E2 pretreatment reduces lung inflammation after intestinal I/R and exerts these effects by modulating eNOS protein expression in the lungs.
- ESTRADIOL MODULATES LOCAL GUT INJURY INDUCED BY INTESTINAL ISCHEMIA-REPERFUSION IN MALE RATS(2017) RICARDO-DA-SILVA, Fernanda Yamamoto; FANTOZZI, Evelyn Thais; RODRIGUES-GARBIN, Sara; OLIVEIRA-FILHO, Ricardo Martins; VARGAFTIG, Bernardo Boris; BREITHAUPT-FALOPPA, Ana Cristina; LIMA, Wothan Tavares deIntestinal ischemia and reperfusion (I/R) triggers a systemic inflammatory response characterized by leukocyte mobilization from the bone marrow, release of cytokines to the circulation, and increased microvascular permeability, leading to high mortality. Females have shown attenuated inflammatory response to trauma when compared with males, indicatinga role for female sex hormones in this process. Here, we have evaluated the effect of estradiol on the local gut injury induced by I/R in male rats. I/R was induced by the clamping of the superior mesenteric artery for 45 min, followed by 2 h of reperfusion. Agroup received 17 beta-estradiol (280 mu g/kg, i.v., single dose) at 30 min of ischemia. Morphometric analysis of the gut showed I/R induced a reduction of villous height that was prevented by estradiol. White blood cells, notably granulocytes, were mobilized from the circulation to the intestine by I/R, which was also prevented by estradiol treatment. Groups had the intestine wrapped in a plastic bag to collect intestinal fluid, where leukocytescount, TNF-alpha, and IL-10 levels were increased by I/R. Serum chemokines (CINC-1, MIP-1 alpha, MIP-2), ICAM-1 expression in the mesenteric tissue, and neutrophils spontaneous migration measured in vitro were also increased after I/R. Estradiol treatment reduced leukocytes numbers and TNF-alpha on intestinal fluid, serum chemokine release and also downregulated MIP-1 alpha, MIP-2 gene expression, and spontaneous in vitro neutrophil migration. In conclusion, estradiol blunts intestinal injury induced by I/R by modulating chemokines release and leukocyte trafficking.
- ACUTE EFFECTS OF ESTRADIOL ON LUNG INFLAMMATION DUE TO INTESTINAL ISCHEMIC INSULT IN MALE RATS(2014) BREITHAUPT-FALOPPA, Ana Cristina; FANTOZZI, Evelyn Thais; ROMERO, Daniel Cancelli; RODRIGUES, Adriana da Silva; SOUSA, Paulo Thales Rocha de; FRANCO, Adriana Lino dos Santos; OLIVEIRA-FILHO, Ricardo Martins; VARGAFTIG, Bernardo Boris; LIMA, Wothan Tavares deIntestinal ischemia and reperfusion (intestinal I/R) causes acute lung inflammation that is characterized by leukocyte migration, increased lung microvascular permeability, and, in severe forms, noncardiogenic pulmonary edema and acute respiratory distress syndrome. Female sex hormones interfere with immune response, and experimental and clinical evidence shows that females are more resistant than males to organ injury caused by gut trauma. To reduce the lung inflammation caused by intestinal I/R, we have acutely treated male rats with estradiol. Intestinal I/R was performed by the clamping (45 min) of the superior mesenteric artery (SMA), followed by 2 h of intestinal reperfusion (unclamping SMA). Groups of rats received 17 beta estradiol (E2, 280 mu g/kg, i.v., single dose) 30 min after the SMA occlusion (ischemia period) or 1 h after the unclamping of SMA (reperfusion period). Leukocytes influx into the lung and microvascular leakage were assessed by lung myeloperoxidase activity and Evans blue dye extravasation, respectively. The lung expression of adhesion molecules (intercellular adhesion molecule 1, platelet endothelial cell adhesion molecule 1, and vascular cell adhesion molecule [VCAM]) was evaluated by immunohistochemistry. Interleukin 1 beta (IL-1 beta), IL-10, and NOx- concentrations were quantified in supernatants of cultured lung tissue. We have found that intestinal I/R increased the lung myeloperoxidase activity and Evans blue dye extravasation, which were reduced by treatment of rats with E2. Intestinal I/R increased ICAM-1 expression only, and it was decreased by E2 treatment. However, E2 treatment reduced the basal expression of platelet endothelial cell adhesion molecule 1. E2 treatment during intestinal ischemia was effective to reduce the levels of IL-10 and IL-1 beta in explant supernatant, but only IL-10 levels were reduced by E2 at reperfusion phase. The treatment with E2 did not affect NOx- concentration. Taken together, our data suggest that estradiol modulates the lung inflammatory response induced by lung injury, likely by acute effects. Thus, acute estradiol treatment could be considered as a potential therapeutic agent in ischemic events.
- HYPERTONIC SALINE SOLUTION REDUCES MICROCIRCULATORY DYSFUNCTION AND INFLAMMATION IN A RAT MODEL OF BRAIN DEATH(2019) CORREIA, Cristiano de Jesus; ARMSTRONG JR., Roberto; CARVALHO, Priscila Oliveira de; SIMAS, Rafael; SANCHEZ, Daniela Crisina Janolli; BREITHAUPT-FALOPPA, Ana Cristina; SANNOMIYA, Paulina; MOREIRA, Luiz Felipe PinhoBackground: Brain death (BD) induces hemodynamic instability with microcirculatory hypoperfusion, leading to increased organ inflammation and dysfunction. This study investigated the effects of 7.5% hypertonic saline solution (HSS) on mesenteric microcirculatory dysfunction and inflammation in a rat model of BD. Methods: Male Wistar rats were anesthetized and mechanically ventilated. BD was induced by rapidly inflating an intracranial balloon catheter. The rats were randomly divided into: SH, sham-operated rats subjected to trepanation; NS, rats treated with NaCl 0.9%, 4 mL/kg immediately after BD; T-1, rats treated with HSS (NaCl 7.5%, 4 mL/kg) immediately or 60 min after BD, T-60. All groups were analyzed 180 min after the start of the experiment. Results: Rats in BD groups presented with a similar hypertensive peak, followed by hypotension. Proportion of perfused small vessels was decreased in the NS group (46%) compared with the SH group (74%, P = 0.0039). HSS restored the proportion of perfused vessels (T-1 = 71%, P = 0.0018). The anti-endothelial nitric oxide synthase (eNOS) protein expression significantly increased in rats given HSS (T-1, and T-60, P = 0.0002). Similar results were observed regarding endothelin-1 (P<0.0001). Increased numbers of rolling (P = 0.0015) and migrated (P = 0.0063) leukocytes were observed in the NS group compared with the SH group. Rats given HSS demonstrated an overall reduction in leukocyte-endothelial interactions. The ICAM-1 levels increased in the NS group compared with the SH group, and decreased in the HSS-treated groups (P = 0.0002). Conclusions: HSS may improve the density of mesenteric perfused small vessels due to its effects on eNOS and endothelin-1 protein expression, and reduces inflammation by decreasing leukocyte adhesion and migration in a rat model of BD.