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

IF 1.7 Q3 PHARMACOLOGY & PHARMACY

Drug Research Pub Date : 2023-02-01 DOI:10.1055/a-1969-4600

Maryam Shayan, Faezeh Eslami, Ayda Khosravi, Amir Rashidian, Razie Mohammad Jafari, Seyed Farzad Maroufi, Hasti Tashak Golroudbari, Ahmad Reza Dehpour

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引用次数: 2

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.

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昂丹司琼与托吡司琼对视神经挤压损伤的保护作用。

背景:本研究旨在评价钙调磷酸酶抑制剂环孢素、昂丹司琼和托司琼-5-羟色胺(5-HT3R)拮抗剂对大鼠视神经损伤(ONC)的潜在神经保护作用。此外，研究了其有益神经保护作用的潜在信号活动。方法:成年雄性大鼠ONC诱导后即刻玻璃体内注射环孢素(1.6 mM)、昂丹司琼(100 nM)、托司司琼(100 nM)。术后第7天提取大鼠视网膜，采用western blot法检测细胞凋亡调节因子Bax、Bcl-2和钙调磷酸酶的表达。结果:ONC损伤的诱导与Bax和钙调磷酸酶的高表达相关，而Bcl-2的表达明显降低。环孢素(1.6 mM)、昂丹司琼(100 nM)和托异司琼(100 nM)玻璃体内处理可显著减弱Bax和钙调磷酸酶的表达。此外，用这些药物治疗导致视网膜中Bcl-2的表达升高。结论:本研究结果表明，环孢素、昂丹司琼和托司琼对大鼠ONC损伤的保护作用可能是通过直接或通过5-HT3受体抑制细胞凋亡和调节钙调磷酸酶活性来实现的。此外，免疫印迹显示托司琼比昂丹司琼更有效。需要进一步的研究来评估环孢素、昂丹司琼和托烷司琼活性背后的确切机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Research PHARMACOLOGY & PHARMACY-

CiteScore

3.50

自引率

0.00%

发文量

期刊介绍： Drug Research (formerly Arzneimittelforschung) is an international peer-reviewed journal with expedited processing times presenting the very latest research results related to novel and established drug molecules and the evaluation of new drug development. A key focus of the publication is translational medicine and the application of biological discoveries in the development of drugs for use in the clinical environment. Articles and experimental data from across the field of drug research address not only the issue of drug discovery, but also the mathematical and statistical methods for evaluating results from industrial investigations and clinical trials. Publishing twelve times a year, Drug Research includes original research articles as well as reviews, commentaries and short communications in the following areas: analytics applied to clinical trials chemistry and biochemistry clinical and experimental pharmacology drug interactions efficacy testing pharmacodynamics pharmacokinetics teratology toxicology.