Carla Brigagão Pacheco da Silva | University of Sao Paulo (original) (raw)

Papers by Carla Brigagão Pacheco da Silva

Journal of Smooth Muscle Research

Purpose: This study aimed to verify whether Adjuvant-Induced Arthritis (AIA) and/or Orchiectomy (... more Purpose: This study aimed to verify whether Adjuvant-Induced Arthritis (AIA) and/or Orchiectomy (ORX) modify the expression of the Nox1, Nox2 and Nox4 isoforms, the endothelial function or the structure of rat aortas. Methods: Sixty-three Wistar rats were distributed into four groups: 1) Control; 2) ORX; 3) AIA; 4) Orchiectomy plus to Arthritis-induction (ORX/AIA). Thus, 21 days after the onset of AIA (by intradermal injection of Mycobacterium tuberculosis), the presence of Nox1, Nox2 and Nox4, the acetylcholine (ACh)-induced relaxation and the media layer thickness were assessed in the aorta taken from these animals. Results: The Nox1, Nox2 and Nox4 were immunostained in intima, media and adventitia layers of aortas taken from all studied groups and AIA apparently increased this immunostaining. These modifications of Nox1, Nox2 or Nox4 expression, however, were not confirmed by Western blotting. In addition, neither AIA nor ORX changed the endothelial function, but ORX increased the media layer thickness in the studied aortas. Conclusion: The present study showed weak clues of increased expression of Nox1, Nox2 and Nox4 as a result of AIA, as well as of Nox1 reduction caused by ORX. In addition, the endothelial function was not modified in the aortas of these animals by both AIA and/or ORX. On the other hand, ORX increased significantly the aorta media layer thickness in the studied animals, which was apparently mitigated by AIA.

SILVA, C. B. P. Mechanisms underlying the renal toxicity induced by chronic ethanol consumption: ... more SILVA, C. B. P. Mechanisms underlying the renal toxicity induced by chronic ethanol consumption: the role of inducible nitric oxide synthase (iNOS). 2020. 104 f. Thesis (Doctoral).

Nitric Oxide, 2019

Hypertension is a risk factor for erectile dysfunction (ED) and both conditions are associated wi... more Hypertension is a risk factor for erectile dysfunction (ED) and both conditions are associated with oxidative stress. Given that nitrite is described to display antioxidant effects, we hypothesized that treatment with nitrite would exert antioxidant effects attenuating both reactive oxygen species (ROS) generation in the corpora cavernosa (CC) and ED induced by hypertension. Two kidney, one clip (2K1C) hypertension was induced in male Wistar rats. Treatment with sodium nitrite (15 mg/kg/day, p.o., gavage) was initiated two weeks after surgery to induce hypertension and maintained for four weeks. Nitrite abrogated both the decrease in intracavernosal pressure and endothelial dysfunction of the CC induced by hypertension. Treatment with nitrite decreased hypertension-induced ROS generation in the CC assessed in situ using the fluorescent dye dihidroethidium (DHE) and with the lucigenin assay. Western immunoblotting analysis revealed that nitrite prevented the increase in Nox1 expression in the CC from 2K1C rats. Decreased concentrations of hydrogen peroxide (H 2 O 2) were found in the CC from hypertensive rats and treatment with nitrite prevented this response. Treatment with nitrite increased the fluorescence of DAF-2DA in the CC from sham-operated rats and restored nitric oxide (NO) levels in the CC from 2K1C rats. In summary, we found novel evidence that nitrite reversed the decrease in intracavernosal pressure induced by 2K1C hypertension. This response was partially attributed to the antioxidant effect of nitrite that blunted ROS generation and endothelial dysfunction in the CC. In addition, nitrite-derived NO may have promoted direct protective actions against hypertension-induced CC dysfunction.

Revista do Instituto de Medicina Tropical de São Paulo, 2014

Currently multiresistant Staphylococcus aureus is one common cause of infections with high rates ... more Currently multiresistant Staphylococcus aureus is one common cause of infections with high rates of morbidity and mortality worldwide, which directs scientific endeavors in search for novel antimicrobials. In this study, nine extracts from Bidens pilosa (root, stem, flower and leaves) and Annona crassiflora (rind fruit, stem, leaves, seed and pulp) were obtained with ethanol: water (7:3, v/v) and their in vitro antibacterial activity evaluated through both the agar diffusion and broth microdilution methods against 60 Oxacillin Resistant S. aureus (ORSA) strains and against S. aureus ATCC6538. The extracts from B. pilosa and A. crassiflora inhibited the growth of the ORSA isolates in both methods. Leaves of B. pilosa presented mean of the inhibition zone diameters significantly higher than chlorexidine 0.12% against ORSA, and the extracts were more active against S. aureus ATCC (p < 0.05). Parallel, toxicity testing by using MTT method and phytochemical screening were assessed, an...

American Journal of Physiology-Heart and Circulatory Physiology, 2021

Ethanol consumption represents a significant public health problem, and excessive ethanol intake ... more Ethanol consumption represents a significant public health problem, and excessive ethanol intake is a risk factor for cardiovascular disease (CVD), one of the leading causes of death and disability worldwide. The mechanisms underlying the effects of ethanol on the cardiovascular system are complex and not fully comprehended. The gut microbiota and their metabolites are indispensable symbionts essential for health and homeostasis and therefore, have emerged as potential contributors to ethanol-induced cardiovascular system dysfunction. By mechanisms that are not completely understood, the gut microbiota modulates the immune system and activates several signaling pathways that stimulate inflammatory responses, which in turn, contribute to the development and progression of CVD. This review summarizes preclinical and clinical evidence on the effects of ethanol in the gut microbiota and discusses the mechanisms by which ethanol-induced gut dysbiosis leads to the activation of the immune...

Canadian Journal of Physiology and Pharmacology, 2021

Cardiac damage during the acute phase of Chagas disease (CD) is associated with an increase in pr... more Cardiac damage during the acute phase of Chagas disease (CD) is associated with an increase in pro-inflammatory markers and oxidative stress. Melatonin (MEL) has emerged as a promising therapy for CD due to its antioxidant and immunomodulatory properties; however, the protective action of MEL in the cardiac tissue, as well as its direct action on the parasite cycle, is not fully understood. We investigated the effects of MEL on heart parasitism in mice infected with Trypanosoma cruzi and also its effects on the parasitic proliferation in vitro. Our in vivo study showed that MEL reduced circulating parasitemia load, but did not control tissue (heart, liver, and spleen) parasitism in mice. MEL did not prevent the redox imbalance in the left ventricle of infected mice. Our in vitro findings showed that MEL did not inhibit parasites replication within cells, but rather increased their release from cells. MEL did not control parasitism load in the heart or prevent the cardiac redox imbal...

Canadian journal of physiology and pharmacology, 2020

We tested the hypothesis that ethanol consumption would aggravate the renal damage induced by cyc... more We tested the hypothesis that ethanol consumption would aggravate the renal damage induced by cyclophosphamide (CYP). Male C57BL/6J mice from control (n=8) and CYP (n=12) groups had free access to filtered water and standard rodent chow for 12 weeks. Then, 24 h before euthanasia mice received an intraperitoneal injection of saline or CYP (300 mg/kg). Mice from ethanol (n=8) and CYP + ethanol (n=12) groups had free access to increasing doses of ethanol for 12 weeks. Twenty four hours before euthanasia, mice from ethanol and CYP + ethanol groups received an intraperitoneal injection of saline or CYP, respectively. Ethanol, CYP or the association of both drugs augmented serum levels of creatinine and increased the levels of superoxide (O2•-) generation and thiobarbituric acid reactive substances (TBARS) in the renal cortex. Up-regulation of Nox4 and increased activity of superoxide dismutase (SOD) were detected in the renal cortex of mice treated with ethanol, CYP or the combination of...

Cardiovascular Toxicology, 2020

Changes in redox state are described in the early stages of ethanol-induced cardiac toxicity. Her... more Changes in redox state are described in the early stages of ethanol-induced cardiac toxicity. Here, we evaluated whether nebivolol would abrogate ethanol-induced redox imbalance in the heart. Male Wistar rats were treated with a solution of ethanol (20% v/v) for 3 weeks. Treatment with nebivolol (10 mg/kg/day; p.o. gavage) prevented the increase of both superoxide (O2•-) and thiobarbituric acid reactive substances (TBARS) in the left ventricle of rats chronically treated with ethanol. Neither ethanol nor nebivolol affected the expression of Nox4, p47phox, or Rac-1. Nebivolol prevented ethanol-induced increase of Nox2 expression in the left ventricle. Superoxide dismutase (SOD) activity as well as the concentration of reduced glutathione (GSH) was not altered by ethanol or nebivolol. Augmented catalase activity was detected in the left ventricle of both ethanol- and nebivolol-treated rats. Treatment with nebivolol, but not ethanol increased eNOS expression in the left ventricle. No changes in the activity of matrix metalloproteinase (MMP)2 or in the expressions of MMP2, MMP9, and tissue inhibitor metalloproteinase (TIMP)1 were detected after treatment with ethanol or nebivolol. However, ethanol increased the expression of TIMP2, and this response was prevented by nebivolol. Our results provided novel insights into the mechanisms underlying the early stages of the cardiac injury induced by ethanol consumption. We demonstrated that Nox2/NADPH oxidase-derived ROS play a role in ethanol-induced lipoperoxidation and that this response was prevented by nebivolol. In addition, we provided evidence that MMPs are not activated in the early stages of ethanol-induced cardiac toxicity.

Life Sciences, 2020

AIMS Reactive oxygen species (ROS) and pro-inflammatory cytokines play a critical role in organ d... more AIMS Reactive oxygen species (ROS) and pro-inflammatory cytokines play a critical role in organ damage induced by ethanol consumption. Interleukin (IL)-10 maintain tissue homeostasis through restriction of excessive inflammatory responses and inhibition of ROS generation. These responses limit unnecessary tissue damage in the cardiorenal system. We hypothesized that IL-10 would limit the deleterious effects induced by ethanol consumption in the cardiorenal system. MATERIALS AND METHODS Male C57BL/6J wild-type (WT) or IL10-deficient mice (IL-10-/-) were treated with ethanol (20% v/v) for 6 weeks. KEY FINDINGS IL-10 deficiency was associated with an increased mortality rate. Ethanol consumption decreased plasma levels of IL-10 in WT mice. Increased levels of IL-6 were detected in the aorta from IL-10-deficient mice, but not WT mice. No alterations in the levels of urea, creatinine, sodium, potassium or creatine kinase (CK)-MB were found after treatment with ethanol. Augmented concentration of thiobarbituric acid reactive substances (TBARS) was found in the left ventricle (LV) of IL-10-deficient mice, but not WT mice. Increased levels of superoxide anion (O2-) were found in the renal cortex of both WT and IL-10-deficient mice. Renal cortex from WT mice chronically treated with ethanol showed decreased levels of H2O2. No changes in the expression of Nox1, Nox4 or catalase were found in the renal cortex from ethanol-treated mice. SIGNIFICANCE IL-10 limited the production of ROS and the synthesis of pro-inflammatory cytokines induced by ethanol in the cardiorenal system. These findings provided novel evidence that IL-10 counteracted the initial mechanisms whereby ethanol induces its cardiorenal damages.

European Journal of Pharmacology, 2019

Cytokine, 2019

We evaluated the role of tumor necrosis factor (TNF)-α receptor 1 (TNFR1) on ethanol-induced card... more We evaluated the role of tumor necrosis factor (TNF)-α receptor 1 (TNFR1) on ethanol-induced cardiac dysfunction. Male C57BL/6J wild-type (WT) or TNFR1-deficient mice (TNFR1 −/−) were treated with ethanol (20% v/v) for 10 weeks. Increased protein expression of TNFR1 and NFκB p65 was detected in the left ventricle (LV) of WT mice chronically treated with ethanol. Echocardiographic analysis showed that ethanol consumption increased left ventricular posterior wall end-diastolic diameter and left ventricular posterior wall end-systolic diameter in WT, but not TNFR1 −/− mice. Increased levels of TNF-α, interleukin (IL)-6, superoxide anion (O 2 %−), thiobarbituric acid reactive substances (TBARS) as well as increased nitrotyrosine immunostaining were detected in the LV from WT, but not TNFR1 −/− mice. Conversely, treatment with ethanol decreased nitrate/ nitrite (NOx) concentration in the LV. Histopathological analysis showed that ethanol did not induce inflammatory infiltrates, necrosis or edema in the LV. No differences in the ventricular expression of iNOS, Nox2 or COX-2 as well as in the activity of superoxide dismutase (SOD), myeloperoxidase (MPO) and N-acetyl-beta-Dglucosaminidase (NAG) were found after treatment with ethanol. Our study provided novel evidence that ethanol consumption augmented the production of reactive oxygen species (ROS) and the synthesis of proinflammatory proteins in the LV through TNFR1-dependent mechanisms. These findings provided novel mechanistic insights about the contribution of TNFR1 in the initial steps of the cardiac damage induced by ethanol.

Journal of pharmacological and toxicological methods, Jan 9, 2016

There is certainly a great benefit to treatment with antineoplastic drugs for cancer patients wit... more There is certainly a great benefit to treatment with antineoplastic drugs for cancer patients with a life-threatening disease. However, for the workers who are exposed to these agents as part of their work practice, precautions should be taken to eliminate or reduce exposure as much as possible. The aim of this study is to develop and validate a wipe sampling procedure followed by liquid chromatographic separation with electrospray ionization and a tandem mass spectrometric detection method for the simultaneous determination of cyclophosphamide (CP), docetaxel (DOC), doxorubicin (DOXO) and 5-fluorouracil (5-FU). The chromatographic separation was carried out in 15min by applying a gradient elution of 0.1% formic acid and acetonitrile. MS/MS was performed on a triple quadrupole instrument in the multiple reaction monitoring (MRM) mode. The analytical range was linear between 3.5 to 300ng/mL for CP, 4 to 300ng/mL for DOC and DOXO and 2 to 300ng/mL for 5-FU. The present method offers a...