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Amitriptyline Downregulates Chronic Inflammatory Response to Biomaterial in Mice

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.

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Acknowledgments

The western blots images shown in this work were obtained using Typhoon™ FLA 9000 scanner equipment in the Centro de Aquisição e Processamento de Imagens (CAPI-ICB/UFMG).

Funding

The Brazilian Research Support from FAPEMIG and CNPq funded this project (grant number: APQ-01140-13 and 448853/2014-0).

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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Karina Scheuermann, Laura Alejandra Ariza Orellano, Luciano Santos Aggum Capettini, Silvia Passos Andrade, and Paula Peixoto Campos. The first draft of the manuscript was written by Paula Peixoto Campos and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Paula Peixoto Campos.

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Scheuermann, K., Orellano, L.A.A., Viana, C.T.R. et al. Amitriptyline Downregulates Chronic Inflammatory Response to Biomaterial in Mice. Inflammation 44, 580–591 (2021). https://doi.org/10.1007/s10753-020-01356-0

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KEY WORDS

  • amitriptyline
  • anti-inflammatory
  • sponge model
  • chronic inflammation