Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA128

Poster Communications

Caustic oesophageal burn injury in rats is alleviated by the antifibrotic drug halofuginone

K. Karadeniz Cerit2, B. Karakoyun3, E. F. Bahadir1, M. Yuksel4, N. Bulbul5, F. Ercan5, T. Dagli2, B. C. Yegen1

1. Physiology, Marmara University School of Medicine, Istanbul, Turkey. 2. Peadiatric Surgery, Marmara University School of Medicine, Istanbul, Turkey. 3. Basic Health Sciences, Marmara University Health Sciences Faculty, Istanbul, Turkey. 4. Medical Laboratory, Marmara University Vocational School of Health Related Professions, Istanbul, Turkey. 5. Histology & Embryology, Marmara University, School of Medicine,, Istanbul, Turkey.

Background: Accidental ingestion of corrosive substances in children, leading to oesophageal strictures, is still an important health issue in developing countries. We have previously shown that halofuginone, a specific inhibitor of collagen type 1 synthesis, is beneficial in ameliorating oxidative damage in different rat models. The aim of this study is to evaluate the anti-inflammatory and antifibrotic effects of halofuginone in caustic oesophageal burn injury in rats. Materials and Methods: Under ketamine (100 mg kg−1, I.P.) and chlorpromazine (0.75mg kg−1, I.P.) anaesthesia, caustic oesophageal burn injury (EBI) was produced in male Wistar albino rats by the application of 37.5% NaOH onto the distal oesophagus (n=40), while only 0.09% NaCl solution was instilled in the control group (n=8). Until the rats were decapitated on the 3rd day (early group) or on the 28th day (late group) of EBI induction, rats were treated intraperitoneally with saline or halofuginone (100 µg/kg/day) on each day (early group) or on alternate days (late group). Nitric oxide (NO), peroxynitrite (ONOO-), nuclear factor (NF)-kB, caspase-3 and luminol- and lucigenin-enhanced chemiluminescence (CL) levels were measured in the oesophageal tissues. Tissue samples were prepared for histopathological evaluation. Statistical analysis was performed by ANOVA and Student's t-tests. Results: NFkB and caspase-3 levels were not different among groups. Microscopic damage scores were elevated in both early and late EBI groups (p<0.001), while halofuginone treatment reduced the microscopic damage scores in both groups. NO, ONOO- and CL levels, which were elevated in the saline-treated early EBI group (p<0.05-0.001), were suppressed by halofuginone treatment (p<0.05). EBI-induced elevations in NO and ONOO- levels were reduced in the late period of saline-treated group, while these levels were increased by halofuginone (p<0.001). EBI-induced high CL levels were not changed in the late groups treated with either saline or halofuginone. Conclusion: In the early period, halofuginone alleviated injury of the caustic oesophagus by reducing the release of oxygen/nitrogen-derived free radicals. Although halofuginone was still efficient in reducing EBI in the chronic phase, its oxidant scavenging effect was replaced by enhanced production of nitrogen radicals, suggesting the contribution of other anti-inflammatory mechanisms.

Where applicable, experiments conform with Society ethical requirements