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Halofuginone improves caustic-induced oxidative injury of esophagus in rats

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Abstract

Background

The aim of this study is to evaluate the anti-inflammatory and anti-fibrotic effects of halofuginone in caustic esophageal burn injury in rats.

Materials and methods

Corrosive esophageal injury (CEI) was produced in male Wistar albino rats by instilling NaOH solution (1 ml, 37.5%) into the distal esophagus. Rats were decapitated on the 3rd day (early group) or 28th day (late group), and treated daily with either saline or halofuginone (100 µg/kg/day; i.p.), continued on alternate days after the third day. Histopathological evaluation and measurement of nitric oxide (NO), peroxynitrite (ONOO-) and oxygen-derived radicals by chemiluminescence (CL) were made in the distal 2 cm of the esophagus. Non-irrigated proximal esophageal samples were assessed for the levels of nuclear factor (NF)-κB, caspase-3, glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) activity.

Results

GSH, MDA, NF-κB and caspase-3 levels, and MPO activity in the proximal esophagus were not different among groups. Increased number of TUNEL (+) cells in the irrigated esophagus of the early and late caustic injury groups was reduced by halofuginone treatment. High microscopic damage scores in both early and late CEI groups were decreased with halofuginone treatment. NO, ONOO- and CL levels, which were elevated in the saline-treated early CEI group, were reduced by halofuginone treatment, but reduced NO and ONOO- levels in the late period of saline-treated group were increased by halofuginone.

Conclusion

In addition to its anti-fibrotic effects, current findings demonstrate that halofuginone exerts antioxidant and anti-apoptotic actions and supports therapeutic potential for halofuginone in CEI-induced oxidative stress.

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Acknowledgements

The authors acknowledge Merve Evren, PhD Candidate at Ege University Natural and Applied Sciences Department of Biotechnology, for the preparation of the excellent medical illustration (merveulu@gmail.com). This work was supported by a grant from Marmara University Research Fund. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Authors and Affiliations

  1. Department of Pediatric Surgery, School of Medicine, Marmara University, Fevzi Çakmak Mahallesi, Muhsin Yazicioğlu Caddesi, No: 10, Üst Kaynarca, Pendik, 34899, Istanbul, Turkey

    Kıvılcım Karadeniz Cerit & E. Tolga Dağlı

  2. Department of Physiology, School of Medicine, Marmara University, Istanbul, Turkey

    Elif Bahadır & Berrak Ç. Yeğen

  3. Department of Histology and Embryology, School of Medicine, Marmara University, Istanbul, Turkey

    Nurdan Bülbül & Feriha Ercan

  4. Department of Basic Health Sciences, Marmara University Health Sciences Faculty, Istanbul, Turkey

    Berna Karakoyun

  5. Department of Medical Laboratory, Marmara University Vocational School of Health Related Professions, Istanbul, Turkey

    Meral Yüksel

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  1. Kıvılcım Karadeniz Cerit
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  2. Berna Karakoyun
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  3. Elif Bahadır
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  4. Meral Yüksel
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  7. E. Tolga Dağlı
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Correspondence to Kıvılcım Karadeniz Cerit.

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Ethical Statement

All experimental protocols were approved by the Marmara University Animal Care and Use Committee (06.2014.mar).

Conflict of interest

Authors have no financial, personal, academic or intellectual conflicts of interest to declare, except for the grant obtained from the Marmara University Research Fund, Istanbul, Turkey (SAG-B-100914-0308).

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Cerit, K.K., Karakoyun, B., Bahadır, E. et al. Halofuginone improves caustic-induced oxidative injury of esophagus in rats. Esophagus 15, 59–68 (2018). https://doi.org/10.1007/s10388-017-0594-4

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  • DOI: https://doi.org/10.1007/s10388-017-0594-4

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