Protective Effects of Ondansetron and Tropisetron on Optic Nerve Crush Injury in Rats
Maryam Shayan1 *, Ahmad Reza Dehpour1
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
Abstract: The purpose of this study was to evaluate the potential neuroprotective effect of cyclosporine, ondansetron, and tropisetron, on the optic nerve crush (ONC) injury in rats. Moreover, the underlying signaling activities of their beneficial neuroprotective effects were investigated.
Methods: Adult male rats were treated with intravitreal administration of cyclosporine (1.6 mM), ondansetron (100 nM), and tropisetron (100 nM) immediately after the induction of optic nerve crush. Subsequently, on the 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: Induction of optic nerve crush injury was associated with higher expression of Bax and calcineurin, while Bcl-2 expression was notably 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. Additionally, treatment with these agents resulted in an elevated expression of Bcl-2 in the retina. Moreover, we found that tropisetron is more effective as opposed to ondansetron.
Conclusion: Our findings indicate that ondansetron and tropisetron protect against optic nerve crush injury in rats through suppression of apoptosis and modulation of calcineurin activity directly and via 5-HT3 receptors. Further investigations are needed to evaluate the precise mechanism behind ondansetron and tropisetron activities.
