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Comparing the influence of two immunosuppressants (fingolimod, azathioprine) on wound healing in a rat model of primary and secondary intention wound closure
Author(s) -
Ginestal Ricardo,
PérezKöhler Bárbara,
PérezLópez Paloma,
Rodríguez Marta,
Pascual Gemma,
Cebrián David,
Bellón Juan M.,
GarcíaMoreno Francisca
Publication year - 2018
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/wrr.12685
Subject(s) - azathioprine , medicine , wound healing , fingolimod , saline , wound closure , surgery , placebo , dorsum , anesthesia , pathology , multiple sclerosis , immunology , anatomy , alternative medicine , disease
ABSTRACT In this study, rat models of wound closure by first and second intention were developed to evaluate the influence that two immunosuppressants for treating multiple sclerosis (fingolimod, azathioprine) have on wound healing. Sixty‐three Sprague‐Dawley rats were daily treated with fingolimod (0.6 mg/kg), azathioprine (2.5 mg/kg), or placebo (saline). Following 6 weeks of treatment, a linear incision (1.5 cm) or a circular excisional defect (diameter 1.5 cm) was made on the dorsal skin. The treatments were uninterrupted and after 7 days (incisional) or 21 days (incisional, excisional), animals were euthanized ( n = 7 per group and time‐point). Morphometric (wound closure), histological (stainings), and immunofluorescent studies (macrophages) were performed to evaluate the healing process. For both the incisional and excisional defects, animals treated with fingolimod exhibited a healing process equivalent to that of placebo in terms of collagenization, wound closure, and macrophage response. By comparison, groups treated with azathioprine displayed a delay in healing times which was especially evident in the excisional defect, where inflammatory reaction and collagen deposition in the repair tissue remained active by day 21. These results show that immunosuppressants with a selective mechanism of action (fingolimod) can have less impact on wound healing than their classical nonselective counterparts (azathioprine).