ANA MARIA DE MENDONCA COELHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/37 - Laboratório de Transplante e Cirurgia de Fígado, Hospital das Clínicas, Faculdade de Medicina
13 resultados
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- Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion(2016) VASQUES, Enio Rodrigues; CUNHA, Jose Eduardo Monteiro; COELHO, Ana Maria Mendonca; SAMPIETRE, Sandra N.; PATZINA, Rosely Antunes; ABDO, Emilio Elias; NADER, Helena B.; TERSARIOL, Ivarne L. S.; LIMA, Marcelo Andrade; GODOY, Carlos M. G.; RODRIGUES, Tiago; CHAIB, Eleazar; D'ALBUQUERQUE, Luiz A. C.Background Ischemia and reperfusion (I/R) causes tissue damage and intracellular calcium levels are a factor of cell death. Sodium calcium exchanger (NCX) regulates calcium extrusion and Trisulfated Disaccharide (TD) acts on NCX decreasing intracellular calcium through the inhibition of the exchange inhibitory peptide (XIP). Objectives The aims of this research are to evaluate TD effects in liver injury secondary to I/R in animals and in vitro action on cytosolic calcium of hepatocytes cultures under calcium overload. Methods Wistar rats submitted to partial liver ischemia were divided in groups: Control: (n = 10): surgical manipulation with no liver ischemia; Saline: (n = 15): rats receiving IV saline before reperfusion; and TD: (n = 15): rats receiving IV TD before reperfusion. Four hours after reperfusion, serum levels of AST, ALT, TNF-alpha, IL-6, and IL-10 were measured. Liver tissue samples were collected for mitochondrial function and malondialdehyde (MDA) content. Pulmonary vascular permeability and histologic parameters of liver were determined. TD effect on cytosolic calcium was evaluated in BRL3A hepatic rat cell cultures stimulated by thapsigargin pre and after treatment with TD. Results AST, ALT, cytokines, liver MDA, mitochondrial dysfunction and hepatic histologic injury scores were less in TD group when compared to Saline Group (p<0.05) with no differences in pulmonary vascular permeability. In culture cells, TD diminished the intracellular calcium raise and prevented the calcium increase pre and after treatment with thapsigargin, respectively. Conclusion TD decreases liver cell damage, preserves mitochondrial function and increases hepatic tolerance to I/R injury by calcium extrusion in Ca2+ overload situations.
- THE M-RNA, EXPRESSION OF SERCA2 AND NCX1 IN THE PROCESS OF PHARMACOLOGICAL CELL PROTECTION IN EXPERIMENTAL ACUTE PANCREATITIS INDUCED BY TAUROCHOLATE(2018) VASQUES, Enio Rodrigues; CUNHA, Jose Eduardo Monteiro; KUBRUSLY, Marcia Saldanha; COELHO, Ana Maria; SANPIETRI, Sandra N.; NADER, Helena B.; TERSARIOL, Ivarne L. S.; LIMA, Marcelo A.; CHAIB, Eleazar; D'ALBUQUERQUE, Luiz Augusto CarneiroBackground: Intracellular calcium overload is known to be a precipitating factor of pancreatic cell injury in acute pancreatitis (AP). Intracellular calcium homeostasis depends of Plasmatic Membrane Calcium ATPase (PMCA), Sarcoplasmic Endothelial Reticulum Calcium ATPase 2 (SERCA 2) and the Sodium Calcium Exchanger (NCX1). The antioxidant melatonin (Mel) and Trisulfate Disaccharide (TD) that accelerates NCX1 action could reduce the cell damage determined by the AP. Aim: To evaluate m-RNA expressions of SERCA2 and NCX1 in acute pancreatitis induced by sodium taurocholate in Wistar rats pre-treated with melatonin and/or TD. Methods: Wistar rats were divided in groups: 1) without AP; 2) AP without pre-treatment; 3) AP and Melatonin; 4) AP and TD; 5) AP and Melatonin associated to TD. Pancreatic tissue samples were collected for detection of SERCA2 and NCX1 m-R NA levels by polymerase chain reaction (PCR). Results: Increased m-RNA expression of SERCA2 in the melatonin treated group, without increase of m-RNA expression of the NCX1. The TD did not affect levels of SERCA2 and NCX1 m-RNA expressions. The combined melatonin and TD treatment reduced the m-RNA expression of SERCA2. Conclusions: The effect of melatonin is restricted to increased m-RNA expression of SERCA2. Although TD does not affect gene expression, its action in accelerating calcium exchanger function can explain the slightest expression of SERCA2 m-RNA when associated with Melatonin, perhaps by a joint action of drugs with different and but possibly complementary mechanisms.
- Pentoxifylline enhances the protective effects of hypertonic saline solution on liver ischemia reperfusion injury through inhibition of oxidative stress(2014) ROCHA-SANTOS, Vinicius; FIGUEIRA, Estela R. R.; ROCHA-FILHO, Joel A.; COELHO, Ana M. M.; PINHEIRO, Rafael Soraes; BACCHELLA, Telesforo; MACHADO, Marcel C. C.; D'ALBUQUERQUE, Luiz A. C.BACKGROUND: Liver ischemia reperfiision (IR) injury triggers a systemic inflammatory response and is the main cause of organ dysfunction and adverse postoperative outcomes after liver surgery. Pentoxifylline (PTX) and h-ypertonic saline solution (HTS) have been identified to have beneficial effects against IR injury This study aimed to investigate if the addition of PTX to HTS is superior to HTS alone for the prevention of liver IR injury. METHODS: Male Wistar rats were allocated into three groups. Control rats underwent 60 minutes. of partial liver ischemia, HTS rats were treated with 0.4 mL/kg of intravenous 7.5% NaC1 15 minutes before reperfusion, and HPTX group were treated with 7.5% NaC1 plus 25 mg/kg of PTX 15 minutes before reperfusion. Samples were collected after reperfusion for determination of ALT, AST, TNF-alpha, IL-6, IL-10, mitochondrial respiration, lipid peroxidation, pulmonary permeability and myeloperoxidase. RESULTS: HPTX significantly decreased TNF-alpha 30 minutes after reperfusion. HPTX and HTS significantly decreased ALT, AST, IL-6, mitochondrial dysfunction and pulmonary myeloperoxidase 4 hours after reperfusion. Compared with HTS only, HPTX significantly decreased hepatic oxidative stress 4 hours after reperfusion and pulmonary permeability 4 and 12 hours after reperfusion. CONCLUSION: This study showed that PTX added the beneficial effects of HTS on liver IR injury through decreases of hepatic oxidative stress and pulmonary permeability.
- Intestinal barrier dysfunction and increased COX-2 gene expression in the gut of elderly rats with acute pancreatitis(2016) BARBEIRO, Denise Frediani; KOIKE, Marcia Kiyomi; COELHO, Ana Maria Mendonca; SILVA, Fabiano Pinheiro da; MACHADO, Marcel Cerqueira CesarBackground/Objectives: The clinical course of acute pancreatitis can vary from mild to severe. In its most severe manifestation, acute pancreatitis is associated with an exacerbated systemic inflammatory response and high mortality rates. The severe form of acute pancreatitis is more frequent in elderly patients than in young patients, but the mechanisms underlying this difference are still under investigation. Methods: Rats were divided into two groups as follows: Group 1, young rats; and Group 2, old rats. Acute pancreatitis group was induced by a retrograde injection of a sodium taurocholate solution into the biliopancreatic duct. Using this model of acute pancreatic injury, we designed a study to investigate possible differences in microbial translocation and characteristics of the intestinal barrier between elderly and young rats. Results: There was a significantly higher number of bacterial colonies in the pancreas of elderly rats compared with young rats following pancreas injury, which was associated with a more severe local intestinal inflammatory response that included elevated gene expression of COX-2 and a decreased gene expression of tight junction proteins. Conclusions: We conclude that intestinal damage during acute pancreatitis is exacerbated in elderly rats compared with young rats and that COX-2 inhibition could be a potential therapeutic target to offer tailored treatment for acute pancreatitis in the elderly.
- Beneficial effects of adenosine triphosphate-sensitive K+ channel opener on liver ischemia/reperfusion injury(2014) NOGUEIRA, Mateus Antunes; COELHO, Ana Maria Mendonca; SAMPIETRE, Sandra Nassa; PATZINA, Rosely Antunes; SILVA, Fabiano Pinheiro da; D'ALBUQUERQUE, Luiz Augusto Carneiro; MACHADO, Marcel Cerqueira CesarAIM: To investigate the effect of diazoxide administration on liver ischemia/reperfusion injury. METHODS: Wistar male rats underwent partial liver ischemia performed by clamping the pedicle from the medium and left anterior lateral segments for 1 h under mechanical ventilation. They were divided into 3 groups: Control Group, rats submitted to liver manipulation, Saline Group, rats received saline, and Diazoxide Group, rats received intravenous injection diazoxide (3.5 mg/kg) 15 min before liver reperfusion. 4 h and 24 h after reperfusion, blood was collected for determination of aspartate transaminase (AST), alanine transaminase (ALT), tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), nitrite/nitrate, creatinine and tumor growth factor-beta 1 (TGF-beta 1). Liver tissues were assembled for mitochondrial oxidation and phosphorylation, malondialdehyde (MDA) content, and histologic analysis. Pulmonary vascular permeability and myeloperoxidase (MPO) were also determined. RESULTS: Four hours after reperfusion the diazoxide group presented with significant reduction of AST (2009 +/- 257 U/L vs 3523 +/- 424 U/L, P = 0.005); ALT (1794 +/- 295 U/L vs 3316 +/- 413 U/L, P = 0.005); TNF-alpha (17 +/- 9 pg/mL vs 152 +/- 43 pg/mL, P = 0.013; IL-6 (62 +/- 18 pg/mL vs 281 +/- 92 pg/mL); IL-10 (40 +/- 9 pg/mL vs 78 +/- 10 pg/mL P = 0.03), and nitrite/nitrate (3.8 +/- 0.9 mu mol/L vs 10.2 +/- 2.4 mu mol/L, P = 0.025) when compared to the saline group. A significant reduction in liver mitochondrial dysfunction was observed in the diazoxide group compared to the saline group (P < 0.05). No differences in liver MDA content, serum creatinine, pulmonary vascular permeability and MPO activity were observed between groups. Twenty four hours after reperfusion the diazoxide group showed a reduction of AST (495 +/- 78 U/L vs 978 +/- 192 U/L, P = 0.032); ALT (335 +/- 59 U/L vs 742 +/- 182 U/L, P = 0.048), and TGF-beta 1 (11 +/- 1 ng/mL vs 17 +/- 0.5 ng/mL, P = 0.004) serum levels when compared to the saline group. The control group did not present alterations when compared to the diazoxide and saline groups. CONCLUSION: Diazoxide maintains liver mitochondrial function, increases liver tolerance to ischemia/reperfusion injury, and reduces the systemic inflammatory response. These effects require further evaluation for using in a clinical setting.
- Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model(2015) STEFANO, J. T.; PEREIRA, I. V. A.; TORRES, M. M.; BIDA, P. M.; COELHO, A. M. M.; XERFAN, M. P.; COGLIATI, B.; BARBEIRO, D. F.; MAZO, D. F. C.; KUBRUSLY, M. S.; D'ALBUQUERQUE, L. A. C.; SOUZA, H. P.; CARRILHO, F. J.; OLIVEIRA, C. P.Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg.kg(-1).day(-1) by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1 alpha) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1 alpha and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1 alpha expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.
- Local and systemic effects of aging on acute pancreatitis(2019) COELHO, Ana Maria Mendonca; MACHADO, Marcel Cerqueira Cesar; SAMPIETRE, Sandra Nassa; SILVA, Fabiano Pinheiro da; CUNHA, Jose Eduardo Monteiro; D'ALBUQUERQUE, Luiz Augusto CarneiroBackground: /Objectives: Evaluation of the local and systemic effects of aging on the severity of acute pancreatitis (AP) in an experimental rat model in elderly animals. Methods: AP was induced in Wistar rats by intraductal 2.5% taurocholate injection and divided into two groups: Young (3 month old) and Aged (18 month old). Two and 24 h after AP induction blood samples were collected for determinations of amylase, AST, ALT, urea, creatinine, glucose, and of plasma I-FABP. TNF-alpha and IL-6 levels were determined in serum and ascitic fluid. Liver mitochondrial function and malondialdehyde (MDA) contents, pancreas histological analysis, and pulmonar myeloperoxidade (MPO) activity were performed. Bacterial translocation was evaluated by bacterial cultures of pancreas. Results: A significant increase in serum amylase, AST, ALT, urea, creatinine, glucose, I-FABP, and IL-6 levels, and a reduction in serum and ascitic fluid TNF-alpha levels were observed in the aged group compared to the young group. Liver mitochondrial dysfunction, MDA contents, and pulmonary MPO activity were increased in the Aged AP group compared to the Young AP group. Positive bacterial cultures obtained from pancreas tissue in aged group were significantly increased compared to the young group. Acinar necrosis was also increased in aged AP group when compared to young AP group. Conclusion: Aging worsens the course of acute pancreatitis evidenced by increased local and systemic lesions and increased bacterial translocation.
- Do opioid receptors play a role in the pathogenesis of the inflammatory response in acute pancreatitis?(2012) PENIDO, Artur; COELHO, Ana Maria Mendonca; MOLAN, Nilza Trindade; SILVA, Fabiano Pinheiro da; D'ALBUQUERQUE, Luiz Augusto Carneiro; MACHADO, Marcel Cerqueira CesarPURPOSE: To investigate the effect of the opioid blocker naltrexone in the inflammatory response in acute pancreatitis (AP). METHODS: Acute pancreatitis was induced in anesthetized male Wistar rats by retrograde injection of 2.5% sodium taurocholate diluted in 0.5ml saline into the main pancreatic duct. Animals were randomized to the following experimental groups: Control Group (n=9): animals received an intraperitoneal injection of saline solution (0.5ml), 15 minutes before the induction of AP. Naltrexone Group (n=9): animals received an intraperitoneal injection of naltrexone 0.5ml (15 mg/kg), 15 minutes before induction of AP. Peritoneal levels of TNF-alpha and serum levels of IL-6 and amylase were determined The volume of the ascitic fluid was also evaluated. Myeloperoxidase (MPO) activities were analyzed in homogenates of pulmonary tissue. RESULTS: There were no significant differences in the ascitic fluid volume, nor in TNF-alpha and IL-6 levels in the naltrexone group compared to controls. Treatment with naltrexone did not affect the lung MPO activity compared to control group. CONCLUSIONS: The opioid receptors don't play an important role in the pathogenesis of the inflammatory response in acute pancreatitis. If opioids affect leukocytes inflammatory signaling, there are no major implications in the pathogenesis of acute pancreatitis.
- Sevoflurane Preconditioning plus Postconditioning Decreases Inflammatory Response with Hemodynamic Recovery in Experimental Liver Ischemia Reperfusion(2019) FIGUEIRA, Estela Regina Ramos; ROCHA-FILHO, Joel Avancini; LANCHOTTE, Cinthia; COELHO, Ana Maria Mendonca; NAKATANI, Mauro; TATEBE, Eduardo Ryoiti; LIMA, Jonathan Augusto Venceslau; MENDES, Camilla Oliveira; ARAUJO, Bruno Camargo Rocha Paim de; ABDO, Emilio Elias; D'ALBUQUERQUE, Luiz Carneiro; GALVAO, Flavio Henrique FerreiraObjective. The inhalation anesthetic sevoflurane has presented numerous biological activities, including anti-inflammatory properties and protective effects against tissue ischemic injury. This study investigated the metabolic, hemodynamic, and inflammatory effects of sevoflurane pre- and postconditioning for short periods in the rescue of liver ischemia-reperfusion (IR) injury using a rat model. Materials and Methods. Twenty Wistar rats were divided into four groups: sham group, control ischemia group (partial warm liver ischemia for 45min followed by 4h of reperfusion), SPC group (administration of sevoflurane 2.5% for 15min with 5min of washout before liver IR), and SPPoC group (administration of sevoflurane 2.5% for 15min before ischemia and 20min during reperfusion). Results. All animals showed a decrease in the mean arterial pressure (MAP) and portal vein blood flow during ischemia. After 4h of reperfusion, only the SPPoC group had MAP recovery. In both the SPC and SPPoC groups, there was a decrease in the ALT level and an increase in the bicarbonate and potassium serum levels. Only the SPPoC group showed an increase in the arterial blood ionized calcium level and a decrease in the IL-6 level after liver reperfusion. Therefore, this study demonstrated that sevoflurane preconditioning reduces hepatocellular injury and acid-base imbalance in liver ischemia. Furthermore, sevoflurane postconditioning promoted systemic hemodynamic recovery with a decrease in inflammatory response.
- Nitric oxide synthase inhibition reduces albumin induced lung damage in acute pancreatitis(2013) ABDO, Emilio Elias; COELHO, Ana Maria Mendonca; PATZINA, Rosely Antunes; SAMPIETRE, Sandra Nassa; CUNHA, Jose Eduardo Monteiro; MACHADO, Marcel Cerqueira Cesar; D'ALBUQUERQUE, Luiz Augusto CarneiroBackground/objectives: Colloid resuscitation in acute pancreatitis (AP) is a matter of controversy due to the possible deleterious effect on lung function. A previous study demonstrates that albumin administration increases lung damage in burns and this effect can be reversed by inducible nitric oxide synthase (iNOS) inhibition. This study evaluates the effects of S-methylisothiourea (SMT), a specific iNOS inhibitor, on lungs and pancreas of rats with AP receiving intravenous albumin. Methods: AP was induced in Wistar rats by intraductal 5% taurocholate injection. To evaluate the effect of albumin on lung damage, animals received IV saline or human albumin immediately after AP (Groups: Saline and Albumin). To evaluate the effect of iNOS inhibition on lung damage, SMT was given immediately after AP (Group Saline+SMT, and Group Albumin-FSMT). At 12 h after AP induction, serum amylase activity, lung vascular permeability and myeloperoxidase (MPO) activity were evaluated. Lung and pancreas histological analysis were performed. Results: Serum amylase activity, pancreatic edema, lung vascular permeability, MPO activity, and inflammatory infiltration were significantly increased after AP. Albumin administration increased lung vascular permeability, inflammatory infiltration, and pancreatic edema compared to saline administration (p < 0.05). Albumin administration with SMT reduced lung vascular permeability, MPO activity, and inflammatory infiltration compared to albumin administration alone (p < 0.05). Conclusion: Lung and pancreatic damage induced by albumin administration for restoration of plasma volume in AP are reduced by iNOS inhibition. Awareness of this fact may be useful in high-risk patients who need to receive albumin for volume replacement.