Affiliation:
1. Experimental Medicine Research Center, Tehran University of Medical
Sciences, Tehran, Iran
2. Department of Pharmacology, School of Medicine, Tehran University of
Medical Sciences, Tehran, Iran
Abstract
Abstract
Background This study aimed to evaluate the potential neuroprotective
effect of cyclosporine – a calcineurin inhibitor–, ondansetron,
and tropisetron-5-hydroxytryptamine (serotonin) 3 receptor (5-HT3R)
antagonists–, on optic nerve crush (ONC) injury in rats. Moreover,
underlying signaling activities of their beneficial neuroprotective effects were
studied.
Methods Adult male rats were treated with the intravitreal administration
of cyclosporine (1.6 mM), ondansetron (100 nM), and tropisetron
(100 nM) immediately after the induction of ONC. Subsequently, on 7th
day after surgery, the rats’ retinas were extracted, and the expression
of apoptotic regulators (Bax and Bcl-2) and calcineurin were studied by western
blot analysis.
Results The induction of ONC injury was associated to higher expression of
Bax and calcineurin, while Bcl-2 expression was considerably decreased in these
animals. Intravitreal treatment with cyclosporine (1.6 mM), ondansetron
(100 nM), and tropisetron (100 nM) significantly attenuated the
increased expression of Bax and calcineurin. Moreover, the treatment with these
agents resulted in an elevated expression of Bcl-2 in the retina.
Conclusion Our findings indicate that cyclosporine, ondansetron, and
tropisetron protect against ONC injury in rats, possibly via the suppression of
apoptosis and modulation of calcineurin activity directly and via 5-HT3
receptors. Moreover, immunoblotting showed that tropisetron was more effective
as opposed to ondansetron. Further studies are needed to evaluate the precise
mechanism behind cyclosporine, ondansetron, and tropisetron activities.
Funder
Tehran University of Medical Sciences
Iran National
Sciences Foundation
Subject
Drug Discovery,General Medicine
Cited by
3 articles.
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