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Drug Res (Stuttg) 2023; 73(02): 88-94
DOI: 10.1055/a-1969-4600
Original Article

The Possible Protective Effects of Ondansetron and Tropisetron on Optic Nerve Crush Injury in Rats

Maryam Shayan
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
,
Faezeh Eslami
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
,
Ayda Khosravi
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
,
Amir Rashidian
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
,
Razie Mohammad Jafari
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
,
Seyed Farzad Maroufi
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
,
Hasti Tashak Golroudbari
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
,
Ahmad Reza Dehpour 
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
› Author Affiliations
Funding This study was supported by a grant from the Tehran University of Medical Sciences (TUMS) (Grant No. 1400310155306) and Iran National Sciences Foundation (INSF) (Grant No. 96002757).
› Further Information
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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.

Key words

cyclosporine - ondansetron - tropisetron - optic nerve crush (ONC) - calcineurin - 5-HT3 receptor - apoptosis - rat


Publication History

Received: 22 August 2022

Accepted: 24 October 2022

Article published online:
24 November 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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