Amitriptyline Downregulates Chronic Inflammatory Response to Biomaterial in Mice
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ORIGINAL ARTICLE
Amitriptyline Downregulates Chronic Inflammatory Response to Biomaterial in Mice Karina Scheuermann,1 Laura Alejandra Ariza Orellano,1,2 Celso Tarso Rodrigues Viana,1 Clara Tolentino Machado,1 Marcela Guimarães Takahashi Lazari,1 Luciano Santos Aggum Capettini,3 Silvia Passos Andrade,4 and Paula Peixoto Campos 1,5 Received June 3, 2020; accepted October 2, 2020
Abstract— Recent data has signaled that in addition to its therapeutic indications as antidepressant and analgesic, amitriptyline (AM) exerts anti-inflammatory effects in humans and experimental animal models of acute inflammation. We tested the hypothesis that this compound could also modulate the chronic inflammatory process induced by synthetic matrix in mice. Polyether-polyurethane sponge disks were implanted subcutaneously in 9-week-old male C57BL/6 mice. The animals received by oral gavage 5.0 mg/kg of amitriptyline for seven consecutive days in two treatment regimens. In the first series, the treatment was initiated on the day of surgery and the implants removed at day 7 post-implantation. For the assessment of the effect of amitriptyline on chronic inflammation, the treatment was initiated 7 days post-implantation and the sponge discs removed 14 after implantation. The inflammatory markers evaluated, myeloperoxidase - MPO, nitrite content, IL-6, IFN-γ, TNF-α, CXCL1 and CCL2 levels, and NF-κB transcription factor activation were reduced in implants when the treatment began 7 days post-implantation (chronic inflammation). In contrast, only mast cell number, MPO activity and activation of NF-κB pathway decreased when the treatment began soon after implantation (sub-acute inflammation) in 7-day old implants. The anti-inflammatory effects of amitriptyline described here, extend its range of actions as a potential agent able to attenuate long-term inflammatory processes. KEY WORDS: amitriptyline; anti-inflammatory; sponge model; chronic inflammation. 1
Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627– Pampulha, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil 2 Department of Pathology, University of Massachusetts Medical School, 368 Plantation St, Worcester, MA, United States 3 Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil 4 Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil 5 To whom correspondence should be addressed at Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627–Pampulha, Belo Horizonte, Minas Gerais CEP 31270-901, Brazil. E-mail: [email protected]
INTRODUCTION Antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SSRI), and tricyclic antidepressants (TCA), initially used exclusively to treat depression, have bee
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