Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Protective effect of midazolam against convulsion in neonatal rats via down-regulation of LC3 and Beclin-1 expression

Juan Shi¹, Shuzhong Jiang², Qinhua Wang³, Jiajia Hua⁴, Feifan Xu⁵, Delin Gu⁶, Hui Zhou⁷

¹Department of Pediatrics; ²Department of Gastroenterology; ³Animal Laboratory; ⁴Department of Traditional Chinese Medicine; ⁵Department of Clinical Laboratory; ⁶Science and Education Section, The Sixth People's Hospital of Nantong; ⁷Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226011, China.

For correspondence:- Hui Zhou Email: MarcusLaurafBkC@yahoo.com Tel:+8651380886688

Accepted: 24 February 2020 Published: 31 March 2020

Citation: Shi J, Jiang S, Wang Q, Hua J, Xu F, Gu D, et al. Protective effect of midazolam against convulsion in neonatal rats via down-regulation of LC3 and Beclin-1 expression. Trop J Pharm Res 2020; 19(3):557-563 doi: 10.4314/tjpr.v19i3.14

© 2020 The authors.
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Abstract

Purpose: To investigate the effect of midazolam on growth of neurocytes in vitro and in neonatal rats.

Methods: Neurocyte proliferation and activity of lactate dehydrogenase were assessed by MTT and lactate dehydrogenase assays, respectively. Western blotting was used to determine the effect of midazolam on LC3, Bax, p62 and Beclin-1 protein expressions.

Results: The suppression of neurocyte proliferation byconvulsion was alleviated significantly (p < 0.05) by midazolum treatment. Exposure of convulsion model of neurocytes to midazolum suppressed LC3, Bax, p62 and Beclin-1 protein expression. Midazolum exposure of convulsion model of neurocytes suppressed LDH, caspase-3, caspase-8 and caspase-9 activities. The 3-MA (autophagy inhibitor) treatment also significantly (p < 0.05) promoted neurocyte viability after convulsion induction. In convulsion-induced neurocytes, 3-MA exposure suppressed expression of caspase-3/8/9, LC3, Bax, BeclinÃ¢â‚¬â€˜1 and p62, while application of midazolum treatment to the rats with convulsion markedly decreased brain water content and neurocyte apoptosis (p < 0.05). Treatment with midazolum inhibited LC3, p62 and BeclinÃ¢â‚¬â€˜1 expression in the rat model of convulsion.

Conclusion: Midazolum promotes neurocyte proliferation and inhibits edema development via down-regulation of autophagy. Therefore, midazolum can potentially be used for the treatment of convulsion, but further studies need to be carried out first.

Keywords: Convulsion, Neurocytes, Caspase, Autophagy, Mitochondrial pathway