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Amitriptyline attenuates bleomycin-induced pulmonary fibrosis: modulation of the expression of NF-κβ, iNOS, and Nrf2

  • Mai A. ZaafanEmail author
  • Ahmed R. Haridy
  • Amr M. Abdelhamid
Original Article

Abstract

Amitriptyline is a tricyclic antidepressant that was suggested to have antifibrotic potential. The current study aimed to investigate the modulatory effects of amitriptyline on bleomycin-induced pulmonary fibrosis in rats. Rats were randomly assigned into 4 groups: normal control, bleomycin control, amitriptyline+bleomycin, and amitriptyline only treated group. Lung injury was evaluated through the histological examination and immunohistochemical detection of α-smooth muscle actin (α-SMA) in lung tissue, in addition to the biochemical assessment of pulmonary contents of hydroxyproline and transforming growth factor beta-1 (TGF-β1). In addition, the following parameters were investigated for studying the possible mechanisms of amitriptyline antifibrotic effect: inducible nitric oxide synthase (iNOS), nuclear factor-κβ (NF-κβ), tumor necrosis factor-alpha (TNF-α), serpine-1, p53, nuclear factor erythroid 2-related factor 2 (Nrf2), lipid peroxides, and reduced glutathione (GSH). Amitriptyline exhibited potent antifibrotic effect that was reflected upon the histopathological examination and through its ability to suppress all the fibrotic parameters. Amitriptyline successfully suppressed the expression of NF-κβ, Nrf2, iNOS, and p53 in lung tissues besides the inhibition of other oxidative stress and inflammatory mediators. Amitriptyline could be a promising treatment to pulmonary fibrosis. Amitriptyline not only prevents the depression and its drawbacks in patients suffering from pulmonary fibrosis but also it can suppress fibrosis through variable mechanisms mainly via inhibition of NF-κβ/TNF-α/TGF-β pathway in addition to inhibition of Nrf2 and iNOS expression.

Keywords

Amitriptyline Pulmonary fibrosis Nuclear factor-κβ Nrf2 iNOS 

Notes

Acknowledgments

The authors are very grateful to Dr. Adel M. Bakeer, Professor of Pathology, Faculty of Veterinary Medicine, Cairo University, for examining and interpreting histopathologic aspects of this study. In addition, the authors are very grateful to our dear students; Marina Rafeal, Aghaby Youhana and Mahmoud Ismail who helped in the practical part of the study.

Author contribution

MA and AR conceived and designed the research. MA and AM conducted experiments. AM and AR analyzed data. MA wrote the manuscript. All authors read and approved the manuscript.

Compliance with ethical standards

The study was done with compliance to the ethics standards and approval from the ethics committee of the October University for Modern Sciences and Arts, Egypt.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Pharmacology and Toxicology Department, Faculty of PharmacyOctober University for Modern Sciences and Arts (MSA)6th of OctoberEgypt
  2. 2.Biochemistry Department, Faculty of PharmacyOctober University for Modern Sciences and Arts (MSA)6th of OctoberEgypt

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