Alessandra Hubner de Souza
Universidade Luterana do Brasil
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Featured researches published by Alessandra Hubner de Souza.
Rheumatology | 2014
Diana A. Koch; Rodrigo B. M. Silva; Alessandra Hubner de Souza; Carlos E. Leite; Natália F. Nicoletti; Maria M. Campos; Stefan Laufer; Fernanda Bueno Morrone
OBJECTIVE Mitogen-activated protein kinase (MAPK) p38 inhibitors have entered the clinical phase, although many of them have failed due to high toxicity and lack of efficacy. In the present study we compared the effects of the selective p38 inhibitor ML3403 and the dual p38-PDE4 inhibitor CBS-3595, on inflammatory and nociceptive parameters in a model of polyarthritis in rats. METHODS Male Wistar rats (180-200 g) were used for the complete Freunds adjuvant (CFA)-induced arthritis model and they were evaluated at 14-21 days. We also analysed the effects of these pharmacological tools on liver and gastrointestinal toxicity and on cytokine levels. RESULTS Repeated CBS-3595 (3 mg/kg) or ML3403 (10 mg/kg) administration produced significant anti-inflammatory actions in the chronic arthritis model induced by CFA. CBS-3595 and ML3403 treatment also markedly reduced the production of the proinflammatory cytokine IL-6 in the paw tissue, whereas it widely increased the levels of the anti-inflammatory cytokine IL-10. Moreover, CBS-3595 produced partial anti-allodynic effects in the CFA model at 4 and 8 days after treatment. Notably, ML3403 and CBS-3595 did not show marked signs of hepatoxicity, as supported by unaltered histological observations in the liver sections. Finally, both compounds were safe in the gastrointestinal tract, according to evaluation of intestinal biopsies. CONCLUSION CBS-3595 displayed a superior profile regarding its anti-inflammatory effects. Thus p38 MAPK/PDE4 blocking might well constitute a relevant strategy for the treatment of RA.
Toxicon | 2015
Juliana Figueira da Silva; Célio José Castro-Junior; Sara Marchesan Oliveira; Gerusa Duarte Dalmolin; Cássia Regina Silva; Luciene B. Vieira; Danuza Montijo Diniz; Marta N. Cordeiro; Juliano Ferreira; Alessandra Hubner de Souza; Marcus V. Gomez
Venom-derived peptides constitute a unique source of drug prototypes for the pain management. Many of them can modulate voltage-gated calcium channels that are central in the processing of pain sensation. PhTx3-4 is a peptide isolated from Phoneutria nigriventer venom, which blocks high voltage-activated calcium channels with low specificity, thereby leading to neuroprotection in models of ischemia in vitro. The aim of the present work was evaluating the potential of intrathecal PhTx3-4 in the reversal of different nociceptive states in mice, furthermore assessing the potential of PhTx3-4 in triggering motor side effects. We found that bellow 100 pmol/site, PhTx3-4 did not cause major motor side effects. By comparison, ω-conotoxin MVIIA and ω-conotoxin MVIIC triggered motor side effects at the doses of 10 and 100 pmol/site, respectively. Also, PhTx3-4 (30 pmol/site) caused no significant alterations in the forced locomotor activity test (rotarod) and in the exploratory activity test (versamax). In a model of inflammatory persistent pain (formalin test), PhTx3-4 reversed nociceptive behavior both pre or post-administered, although this effect was observed only at the inflammatory phase of the test and not at the neurogenic phase. Comparatively, ω-conotoxin MVIIC was effective only when post-administered in the formalin test. Nonetheless, PhTx3-4 treatment was devoid of action in acute nociceptive thermal model (hotplate test), whereas morphine showed efficacy in this test. Efficacy of PhTx3-4 in the formalin test was associated with inhibition of formalin-induced glutamate release in the cerebrospinal fluid. PhTx3-4, but not ω-conotoxin MVIIC, reversed NMDA-induced nociceptive behavior indicating a putative role of PhTx3-4 at ionotropic glutamate receptors. Finally, we observed efficacy of PhTx3-4 in ameliorating mechanical hypersensitivity induced by paw incision, a post-operative and more clinically relevant pain model. Taken together, our data show that PhTx3-4 possesses antinociceptive effect in different models of pain in mice, suggesting that this toxin may serve as drug prototype for pain control.
Toxicon | 2014
Alessandra Hubner de Souza; Aírton Martins da Costa Lopes; Célio J. Castro; Elizete Maria Rita Pereira; Caroline Peres Klein; Claudio Antonio da Silva; Juliana Figueira da Silva; Juliano Ferreira; Marcus V. Gomez
This study investigated the effects of Phα1β, pregabalin and diclofenac using an animal model of fibromyalgia (FM). Repeated administration of reserpine (0.25 mg/kg sc) once daily for three consecutive days significantly decreased thermal hyperalgesia, mechanical allodynia, and dopamine and serotonin content in the brain on the 4th day. Phα1β and pregabalin treatment completely reverted the mechanical allodynia and thermal hyperalgesia induced by reserpine treatment on the 4th day, but diclofenac was ineffective. Reserpine treatment significantly increased the immobility time in the forced swim test, which is indicative of depression in the animals. Phα1β, but not pregabalin, reduced the immobility time (56%), suggesting that Phα1β may control persistent pathological pain in FM.
Toxicon | 2017
Flavia Karine Rigo; Gabriela Trevisan; Samira Dal-Toé De Prá; Marta N. Cordeiro; Márcia H. Borges; Juliana Figueiredo Silva; Flavia Viana Santa Cecilia; Alessandra Hubner de Souza; Gabriela de Oliveira Adamante; Alessandra Marcon Milioli; Célio José de Castro Junior; Juliano Ferreira; Marcus Vinicius Gomez
Abstract The native Ph&agr;1&bgr; – a Voltage‐Gated Calcium Channel (VGCC) blocker – and its Recombinant Version – were both tested in rodent pain models with an intraplantar injections of capsaicin or formalin, a chronic constriction injury, and melanoma cancer related pain. The formalin nociceptive behaviour in the neurogenic phase was not affected by the toxin pre‐treatments, while in the inflammatory phase, Ph&agr;1&bgr; and the Recombinant form caused a significant reduction. The nociception that was triggered by capsaicin, an agonist of the TRPV1 vanilloid receptor, was totally blocked by 100 pmol/site, i.t. of Ph&agr;1&bgr; or the recombinant version. For the neuropathic pain that was induced by a chronic constriction injury of the sciatic nerve, Ph&agr;1&bgr; and its Recombinant reduced the allodynia that was induced by the CCI procedure in the rats and the hypersensitivity lasted for 4 h. Fourteen days after the inoculation of the B16‐F10 melanoma cells in the mice, a marked hyperalgesia was induced in the melanoma cancer pain model. Ph&agr;1&bgr; and the Recombinant form reduced the hyperalgesia with a full reversion at 100 pmol/site i.t. The inhibitory effects of the nociception that was induced by native Ph&agr;1&bgr; and the Recombinant in the studied pain models were not statistically different and they developed with no side effects. HighlightsPh&agr;1&bgr;, a Voltage‐Gated Calcium Channel blocker and the Recombinant Version were both tested in rodent pain models.Both peptides caused antinociception on pain models of chronic chonstriction injury, capsaicin and formalin injections.Ph&agr;1&bgr; and the Recombinant caused full reversion of the hyperalgesia induced by melanoma cancer pain model.The antinociceptive effects of the native Ph&agr;1&bgr; were fully mimicked by the Recombinant, without causing any side effects.
Pharmacology, Biochemistry and Behavior | 2014
Danuza Montijo Diniz; Alessandra Hubner de Souza; Elizete Maria Rita Pereira; Juliana Figueira da Silva; Flávia Karine Rigo; Marco Aurélio Romano-Silva; Nancy Scardua Binda; Célio J. Castro; Marta N. Cordeiro; Juliano Ferreira; Marcus V. Gomez
XVII FÓRUM DE PESQUISA CIENTÍFICA E TECNOLÓGICA | 2017
Luiza Gabriela Rosa; Alessandra Hubner de Souza; Vanessa Gaissler
Revista de Iniciação Científica da ULBRA | 2017
Iasmine Oliveira Berbigier; Luciana Alós Bielefeld; Estela Schiavini Wazenkeski; Mariana Brandalise; Lidiane Santos; Alessandra Hubner de Souza
Revista Saúde e Desenvolvimento | 2017
Andréia Silva Gomes; Karen Magnus; Alessandra Hubner de Souza
3° ENCONTRO ULBRA DE BOLSISTAS CNPQ E FAPERGS | 2017
Joana Morez Silvestri; Camila Fernanda da Silveira Alves; Alessandra Hubner de Souza; Wolnei Caumo; Daniel Simon
3° ENCONTRO ULBRA DE BOLSISTAS CNPQ E FAPERGS | 2017
Gabriela Santana de Oliveira; Camila Fernanda da Silveira Alves; Alessandra Hubner de Souza; Wolnei Caumo; Daniel Simon