Francieli Guolo | Universidade do Extremo Sul Catarinense (original) (raw)

Papers by Francieli Guolo

Mediators of Inflammation, 2015

Asthma represents a public health problem and traditionally is classified as an atopic disease, w... more Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways. Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involved in cytokine production that regulates immunoglobulin synthesis. Recognizing that T cell interaction with antigens/allergens is key to the development of inflammatory diseases, the aim of this study is to evaluate the anti-inflammatory potential of cannabidiol (CBD) in this setting. Asthma was induced in 8-week-old Wistar rats by ovalbumin (OVA). In the last 2 days of OVA challenge animals received CBD (5 mg/kg, i.p.) and were killed 24 hours after. The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-αwere determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels. CB...

Anais da Academia Brasileira de Ciências, 2015

The aim of this study was to determine parameters of NO metabolism in plasma and placenta of pree... more The aim of this study was to determine parameters of NO metabolism in plasma and placenta of preeclamptic (PE) patients. It was conducted a case-control study at São José Hospital, Brazil. Thirty-three PE and 33 normotensive pregnant were included in the study. The diagnosis of PE was established in accordance with the definitions of American College of Obstetricians and Gynecologists. Peripheral venous blood and placenta samples were obtained at postpartum period. Plasma NO levels and SOD activity were significantly lower and endothelin-1 levels and arginase activity were significantly higher in PE women when compared to controls. None of the analyzed parameters were different in the placenta between groups. Our findings suggest that parameters associated with NO metabolism are altered only at the systemic level, but not in placenta of PE patients.

Molecular medicine (Cambridge, Mass.), Jan 26, 2015

Sepsis associated encephalopathy (SAE) is associated with an increased rate of morbidity and mort... more Sepsis associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40-CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40-CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40-CD40L in the brain, and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment i...

Revista Brasileira de terapia intensiva, 2011

Red blood cell transfusions are common in intensive care units. For many years, transfusions of r... more Red blood cell transfusions are common in intensive care units. For many years, transfusions of red blood were thought to have obvious clinical benefits. However, in recent years, the risks and benefits of blood transfusions have been examined more carefully, including the risk of increased morbidity and mortality due to transfusion-related immunomodulation effects. To evaluate red blood cell transfusion effects and the relationship of this procedure to the production of inflammatory cytokines and oxidative damage in critically ill patients admitted to an intensive care unit. For 6 months in 2008, we evaluated patients admitted to an intensive care unit who underwent packed red blood cell transfusions. Pre- and post-transfusion levels of interleukin-6, carbonylated proteins and thiobarbituric acid reactive substances were assessed. Serum post-transfusion interleukin-6 levels were reduced, and thiobarbituric acid reactive substances and carbonylated proteins were significantly increa...

Environmental Toxicology and Pharmacology, 2014

Oxidative damage a b s t r a c t We evaluated the effects green and mate teas on oxidative and DN... more Oxidative damage a b s t r a c t We evaluated the effects green and mate teas on oxidative and DNA damages in rats exposed to ultraviolet radiation. Were utilized 70 adult male Wistar rats that received daily oral or topic green or mate tea treatment during exposed to radiation by seven days. After, animals were killed by decapitation. Thiobarbituric acid-reactive species levels, protein oxidative damage were evaluated in skin and DNA damage in blood. Our results show that the rats exposed to ultraviolet radiation presented DNA damage in blood and increased protein carbonylation and lipid peroxidation in skin. Oral and topic treatment with green tea and mate tea prevented lipid peroxidation, both treatments with mate tea also prevented DNA damage. However, only topic treatment with green tea and mate tea prevented increases in protein carbonylation. Our findings contribute to elucidate the beneficial effects of green tea and mate tea, here in demonstrated by the antioxidant and antigenotoxic properties presented by these teas.

Neurochemistry International, 2009

Major depression is characterized for symptoms at the psychological, behavioral and physiological... more Major depression is characterized for symptoms at the psychological, behavioral and physiological levels. The chronic mild stress model has been used as an animal model of depression. The consumption of sweet food, locomotor activity, body weight, lipid and protein oxidation levels and superoxide dismutase and catalase activities in the rat hippocampus, prefrontal cortex and cortex were assessed in rats exposed

Molecular Neurobiology, 2013

There is no description on the mechanisms associated with blood-brain barrier (BBB) disruption du... more There is no description on the mechanisms associated with blood-brain barrier (BBB) disruption during sepsis development. Thus, we here determined changes in permeability of the BBB in an animal model of severe sepsis and the role of matrix metalloproteinase (MMP)-2 and MMP-9 in the dysfunction of the BBB. Sepsis was induced in Wistar rats by cecal ligation and perforation. BBB permeability was assessed using the Evans blue dye method. The content of MMP-2 and MMP-9 in the cerebral microvessels was determined by western blot. The activity of MMP-2 and MMP-9 was determined using zymography. An inhibitor of MMP-2 and MMP-9 or specific inhibitors of MMP-2 or MMP-9 were administered to define the role of MMPs on BBB permeability, brain inflammatory response, and sepsis-induced cognitive alterations. The increase of BBB permeability is time-related to the increase of MMP-9 and MMP-2 in the microvessels, both in cortex and hippocampus. Using an MMP-2 and MMP-9 inhibitor, or specific MMP-2 or MMP-9 inhibitors, the increase in the permeability of the BBB was reversed. This was associated with lower brain levels of interleukin (IL)-6 and lower oxidative damage. In contrast, only the inhibition of both MMP-9 and MMP-2 was able to improve acute cognitive alterations associated with sepsis. In conclusion, MMP-2 and MMP-9 activation seems to be a major step in BBB dysfunction, but BBB dysfunction seems not to be associated with acute cognitive dysfunction during sepsis development.

Brain, Behavior, and Immunity, 2015

Oxidative stress and inflammation is likely to be a major step in the development of sepsis-assoc... more Oxidative stress and inflammation is likely to be a major step in the development of sepsis-associated encephalopathy (SAE) and long-term cognitive impairment. To date, it is not known whether brain inflammation and oxidative damage are a direct consequence of systemic inflammation or whether these events are driven by brain resident cells, such as microglia. Therefore, the aim of this study is to evaluate the effect of minocycline on behavioral and neuroinflammatory parameters in rats submitted to sepsis. Male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP). The animals were divided into sham-operated (Sham+control), sham-operated plus minocycline (sham+MIN), CLP (CLP+control) and CLP plus minocycline (CLP+MIN) (100 μg/kg, administered as a single intracerebroventricular (ICV) injection). Some animals were killed 24h after surgery to assess the breakdown of the blood brain barrier, cytokine levels, oxidative damage to lipids (TBARS) and proteins in the hippocampus. Some animals were allowed to recover for 10 days when step-down inhibitory avoidance and open-field tasks were performed. Treatment with minocycline prevented an increase in markers of oxidative damage and inflammation in the hippocampus after sepsis. This was associated with an improvement in long-term cognitive performance. In conclusion, we demonstrated that the inhibition of the microglia by an ICV injection of minocycline was able to decrease acute brain oxidative damage and inflammation as well as long-term cognitive impairment in sepsis survivors.

Neuroscience letters, 2015

A growing body of evidence points toward an association between the glutamatergic system, as well... more A growing body of evidence points toward an association between the glutamatergic system, as well as immune system dysregulation and major depression. So, the present study was aimed at evaluating the behavioral and molecular effects of the ketamine, an antagonist of the N-methyl-d-aspartate (NMDA) receptor of glutamate in maternally deprived adult rats. In deprived rats treated with saline, we observed an increase in the immobility time; however, ketamine treatment reversed this effect, decreasing immobility time. In addition, maternal deprivation induced an increase in cytokines: TNF-α and IL-1in serum, and in IL-6 in serum and cerebrospinal fluid (CSF). Interestingly, ketamine treatment reduced the levels of all the cytokines in deprived rats. In conclusion, these findings further support a relationship between immune activation and depression. Considering the action of ketamine, this study suggested that antagonists of the NMDA receptor, such as ketamine, could exert their effec...

Pharmacology Biochemistry and Behavior, 2012

Animal models of chronic stress represent valuable tools by which to investigate the behavioral, ... more Animal models of chronic stress represent valuable tools by which to investigate the behavioral, endocrine and neurobiological changes underlying stress-related psychopathologies, such as major depression, and the efficacy of antidepressant therapies. The present study was aimed at investigating the neurochemical effects of the antidepressant tianeptine in rats exposed to the chronic stress model. To this aim, rats were subjected to 40days of chronic unpredictable stressful stimuli, after which the animals received saline or tianeptine (15mg/kg) once a day for 7days. Additionally, IL-6, IL-1, TNF-α levels and oxidative stress parameters were assessed in the prefrontal cortex (PFC), hippocampus (HPC), amygdala (AMY) and nucleus accumbens (NAc) in all of the experimental groups studied. The results indicated that chronic mild stress and tianeptine did not exercise any effects on cytokines in all of the structures studied; in the PFC and AMY thiobarbituric acid reactive substances (TBARS) levels were decreased in control rats treated with tianeptine in the HPC; superoxide dismutase (SOD) activity was found to have decreased in stressed rats treated with saline in the PFC, HPC, AMY and NAc, and tianeptine reversed this effect; catalase (CAT) activity was found to have decreased in the PFC, HPC and NAc of stressed rats treated with saline, but was shown to have increased in stressed rats treated with tianeptine, and tianeptine also reversed the decreases in CAT activity in stressed rats treated with saline, suggesting that tianeptine exerted antioxidant activity. In conclusion, the present findings open new vistas on the pharmacological activity of tianeptine, in particular, concerning its ability to attenuate oxidative stress.

Neuroscience Letters, 2010

Bacterial meningitis is associated with intense inflammation and also linked to the production of... more Bacterial meningitis is associated with intense inflammation and also linked to the production of reactive oxygen species. To this aim, animals underwent a magna cistern tap and received either sterile saline as a placebo or an equivalent volume of a Streptococcus pneumoniae suspension. The animals began antibiotic therapy 16h after induction. The animals were sacrificed at 24 or 48h post-infection and the hippocampus and cortex were harvested. The activity of the enzymes superoxide dismutase, catalase, and thiobarbituric acid reactive species, protein carbonyls, and free sulphydryl groups were altered, but reversed, in part, by the antibiotic treatment. Our results support the hypothesis that antibiotic treatment prevents, in part, the oxidative stress in the bacterial meningitis induced by Streptococcus pneumoniae.

Neurochemical Research, 2011

We verify the levels of cytokine/chemokine, myeloperoxidase activity, oxidative stress and disrup... more We verify the levels of cytokine/chemokine, myeloperoxidase activity, oxidative stress and disruption of BBB in hippocampus and cortex of the neonate Wistar rats after meningitis by S. agalactiae. In the hippocampus the levels were increased of CINC-1 at 6 h and 12 h, IL-1b at 6, 12 and 24 h, IL-6 at 6, 24 and 96 h, IL-10 at 24, 48 and 96 h and TNF-a at 24 h and 96 h. In the cortex the CINC-1 and IL-1b levels were found increased at 6 h. The MPO activity was significantly elevated at 24, 48 and 98 h in hippocampus and at 6, 12, 24, 48 and 96 h in the cortex. The breakdown of BBB started at 12 h.TBARS levels were elevated in the hippocampus at 6, 12, 24, 48, 72 and 96 h and cortex at 72 and 96 h. Protein carbonyls were elevated in the hippocampus and cortex at 6, 24, 48, 72 and 96 h. There was a decrease of SOD activity in hippocampus and in cortex. Catalase activity was elevated in hippocampus at 6 h and in the cortex at 12 and 96 h. Neonatal bacterial infections of the CNS are severe, the interference with the complex network of cytokines/chemokine, other inflammatory mediators and oxidants tend to aggravate the illness and can be involved in the breakdown of the BBB.

Metabolic Brain Disease, 2011

Contrast-induced nephropathy is a common cause of acute renal failure in hospitalized patients, o... more Contrast-induced nephropathy is a common cause of acute renal failure in hospitalized patients, occurring from 24 to 48 h and up to 5 days after the administration of iodinated contrast media. Encephalopathy may accompany acute renal failure and presents with a complex of symptoms progressing from mild sensorial clouding to delirium and coma. The mechanisms responsible for neurological complications in patients with acute renal failure are still poorly known, but several studies suggest that mitochondrial dysfunction plays a crucial role in the pathogenesis of uremic encephalopathy. Thus, we measured mitochondrial respiratory chain complexes and creatine kinase activities in rat brain and kidney after administration of contrast media. Wistar rats were submitted to 6.0 ml/kg meglumine/sodium diatrizoate administration via the tail vein (acute renal failure induced by contrast media) and saline in an equal volume with the radiocontrast material (control group); 6 days after, the animals were killed and kidney and brain were obtained. The results showed that contrast media administration decreased complexes I and IV activities in cerebral cortex; in prefrontal cortex, complex I activity was inhibited. On the other hand, contrast media administration increased complexes I and II-III activities in hippocampus and striatum and complex IV activity in hippocampus. Moreover, that administration of contrast media also decreased creatine kinase activity in the cerebral cortex. The present findings suggest that the inhibition of mitochondrial respiratory chain complexes and creatine kinase caused by the acute renal failure induced by contrast media administration may be involved in the neurological complications reported in patients and might play a role in the pathogenesis of the encephalopathy caused by acute renal failure.

Journal of Psychiatric Research, 2009

Major depression is a common, serious and recurrent disorder, characterized by symptoms at the ps... more Major depression is a common, serious and recurrent disorder, characterized by symptoms at the psychological, behavioral and physiological levels. Recent studies have suggested that reactive oxygen species (ROS) may play a role in the pathophysiology of bipolar disorder. The chronic mild stress (CMS) rat model has been used as an animal model of depression, since it induces some symptoms of a major depressive episode in humans (i.e. anhedonia). We investigated behavioral, physiological and neurochemical aspects of rats exposed for 40 days to CMS. Sweet food consumption, locomotor activity and body weight were assessed in stressed and control rats. We also investigated the potential involvement of ROS in the CMS model. Superoxide generation in submitochondrial particles from the rat hippocampus, prefrontal cortex and cortex was measured through superoxide-dependent oxidation of epinephrine to adrenochrome in a submitochondrial extract. We report that sweet food intake was reduced in rats subjected to CMS compared to controls. Further, CMS animals failed to gain body weight compared with non-stressed rats. Locomotor activity was not affected in stressed rats. An increase in superoxide production was detected in all brain structures analyzed. However, thiobarbituric acid reactive substances were increased only in cortex. In conclusion, these observations support the view that the CMS model of depression mimics alterations observed in depressed patients. The model affords a useful system in which to test the hypothesis that altered brain energy metabolism is associated with neuropsychiatric disorders.

Intensive Care Medicine, 2008

The aim of this study was investigate the effects of nociceptin/orphanin FQ (N/OFQ) and ([Nphe 1 ... more The aim of this study was investigate the effects of nociceptin/orphanin FQ (N/OFQ) and ([Nphe 1 ,Arg 14 ,Lys 15 ]N/OFQ-NH 2) (UFP-101), the endogenous N/ OFQ peptide receptor (NOP) ligand and a selective NOP antagonist, respectively, in the inflammatory response after cecal ligation and puncture (CLP) model of sepsis in rats. Design: Prospective, controlled experiment. Setting: Animal basic science laboratory. Subjects: Male Wistar rats, weighing 300-350 g. Interventions: Rats subjected to CLP were treated with N/ OFQ (0.001, 0.01 or 0.1 mg/kg) or UFP-101 (0.03, 0.03 or 0.3 mg/kg) subcutaneously administered immediately after surgery. Measurements and main results: Twelve hours after surgery, blood was collected by cardiac puncture and bronchoalveolar (BAL) and peritoneal lavage were performed. In a separate set of experiments mortality was evaluated monitoring CLP rats for 10 days. Our findings showed that UFP-101 (0.03 mg/kg, sc, but not 0.003 mg/ kg) modified parameters related to the systemic inflammatory response by effectively preventing cells migration, bacterial dissemination, and by modulating the release of proinflammatory cytokines and chemokines, and reducing animal mortality in a clinically relevant model of sepsis. By contrast, N/OFQ (0.1 mg/kg, sc) increased mortality in the CLP model. Conclusions: Our findings point to a functional relationship between the N/OFQ-NOP receptor system and inflammatory response in the CLP model of sepsis and suggest that NOP receptor antagonists are worthy of testing as innovative drugs for the treatment of sepsis.

Inflammation Research, 2010

Objective We report the effects of the gastrin-releasing peptide (GRP) receptor antagonist RC-309... more Objective We report the effects of the gastrin-releasing peptide (GRP) receptor antagonist RC-3095 in an acute inflammation model induced by carrageenan. Methods Male Wistar rats received saline or saline containing 2% k-carrageenan into the pleural cavity, with some also receiving RC-3095 3 mg/kg subcutaneously, immediately after surgery. Four hours later, the rats were killed and pleural exudate was obtained for evaluation of total cell count, lactate dehydrogenase activity, total protein, cytokines analysis and nitrite/nitrate concentrations; myeloperoxidase (MPO) activity and oxidative stress were evaluated in the lung. Results RC-3095 exhibited pronounced anti-inflammatory actions by inhibition of leukocyte influx and blockade of MPO, nitrite/nitrate and cytokine levels. Moreover, the results showed that RC-3095 elicits action against oxidative damage in lipids and proteins, as well as increasing cell viability. Conclusion The present findings suggest that GRP plays a role in acute inflammation that can be related with the reduction of oxidative damage and that it could be effective in therapeutic applications.

The Journal of surgical research, Jan 15, 2011

The derangement in oxygen utilization occurring during sepsis is likely to be linked to impaired ... more The derangement in oxygen utilization occurring during sepsis is likely to be linked to impaired mitochondrial functioning. Skeletal muscle comprises 50%-60% of body cell mass and represents the largest organ potentially affected by systemic inflammation. Thus, we investigated whether sepsis induced by cecal ligation and puncture (CLP) modifies mitochondrial activity in respiratory and nonrespiratory skeletal muscle.

Archives of Gynecology and Obstetrics, 2012

Objective To identify the role of Interleukin-6, IL-10 and their epidemiological association in w... more Objective To identify the role of Interleukin-6, IL-10 and their epidemiological association in women with persistence of DNA-HPV. Design and methods A nested case-control study within a longitudinal cohort study. Cervical specimens and blood samples were collected at enrolment from asymptomatic women who looked for a service of public health in a district of Porto Alegre, Brazil. A logistic regression analysis was performed with 95% confidence intervals. The outcome was the persistence of DNA-HPV infection. Results The analysis showed that the age of the first intercourse below 20 years old (OR = 19.65, IC 95% 2.43-68.85), four or more sexual partners during lifetime (OR = 5.67, IC 95% 1.28-24.99), women with a previous altered Pap smear (OR = 10.17, IC 95% 1.80-57.33), marital status (OR = 12.94, IC 95% 2.43-68.85) and IL6 B 3.106 pg/ml were associated with persistence of HPV infection. IL-10 were not associated with the HPV persistence. Conclusion The present study suggests that IL-6 levels may be a marker of HPV DNA persistence, although further investigation is necessary.

American Journal of Respiratory and Critical Care Medicine, 2006

Rationale: Several new therapeutic strategies have been described for the treatment of sepsis, bu... more Rationale: Several new therapeutic strategies have been described for the treatment of sepsis, but to date none are related to alterations in the bombesin/gastrin-releasing peptide (GRP) receptor pathways. Objectives: To determine the effects of a selective GRP receptor antagonist, RC-3095, on cytokine release from macrophages and its in vivo effects in the cecal ligation and puncture (CLP) model of sepsis and in acute lung injury induced by intratracheal instillation of LPS. Methods: We determined the effects of RC-3095 in the CLP model of sepsis and in acute lung injury induced by intratracheal instillation of LPS. In addition, we determined the effects of RC-3095 on tumor necrosis factor-␣ (TNF-␣), interleukin (IL)-1␤, IL-10, and nitric oxide release from activated macrophages. Measurements and Main Results: The GRP antagonist attenuated LPSor CLP-induced TNF-␣, IL-1␤, and nitric oxide release in cultured macrophages and decreased the mRNA levels of inducible nitric oxide synthase. The administration of RC-3095 (0.3 mg/kg) 6 h after sepsis induction improved survival in the CLP model, and diminished lung damage after intratracheal instillation of LPS. These effects were associated with attenuation on the circulating TNF-␣ and IL-1␤ levels and decreased myeloperoxidase activity in several organs. Conclusions: We report that a selective GRP receptor antagonist attenuates the release of proinflammatory cytokines in vitro and in vivo and improves survival in "established" sepsis. These are consistent with the involvement of a new inflammatory pathway relevant to the development of sepsis.

Revista Brasileira de Terapia Intensiva, 2015

The aim of this study was to investigate whether plasma serotonin levels or acetylcholinesterase ... more The aim of this study was to investigate whether plasma serotonin levels or acetylcholinesterase activities determined upon intensive care unit admission could predict the occurrence of acute brain dysfunction in intensive care unit patients. Methods: A prospective cohort study was conducted with a sample of 77 non-consecutive patients observed between May 2009 and September 2010. Delirium was determined using the Confusion Assessment Method for the Intensive Care Unit tool, and the acetylcholinesterase and serotonin measurements were determined from blood samples collected up to a maximum of 24 h after the admission of the patient to the intensive care unit. Results: In the present study, 38 (49.6%) patients developed delirium during their intensive care unit stays. Neither serum acetylcholinesterase activity Conflicts of interest: None.