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Investigation on the Anticonvulsant Potential of Luteolin and Micronized Luteolin in Adult Zebrafish (Danio rerio)

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Abstract

Epilepsy affects around 50 million people worldwide, and an important number of patients (30%) fail to respond to any available antiepileptic drug. Previous studies have shown that luteolin presents a promising potential as an anticonvulsant. On the other hand, different studies showed that luteolin does not promote anticonvulsant effects. Therefore, there is a lack of consensus about the use of luteolin for seizure control. Luteolin low bioavailability could be a limiting factor to obtain better results. Attractively, micronization technology has been applied to improve flavonoids bioavailability. Thus, the present study aimed to investigate the effects of luteolin on its raw form and micronized luteolin in a PTZ-induced seizure model in adult zebrafish (Danio rerio). Our results demonstrate that luteolin and micronized luteolin did not block PTZ-induced seizures in adult zebrafish. Also, luteolin and micronized luteolin did not provoke behavioral changes. Finally, our results show that 24 h after seizure occurrence, no changes were detected for p70S6Kb, interleukin 1β, and caspase-3 transcript levels. Altogether, we failed to observe an anticonvulsant potential of luteolin in adult zebrafish, even in its micronized form. However, we recommend new studies to investigate luteolin benefits in epilepsy.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC 06/2017, Grant Number 2019TR55), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (PIBIC/CNPq; PDE/CNPq), Governo do Estado de Santa Catarina (Programa UNIEDU), and Universidade Comunitária da Região de Chapecó (Unochapecó).

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Correspondence to Anna Maria Siebel.

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11064_2021_3409_MOESM1_ESM.tiff

Supplementary file1 Supplementary figure 1 Differential scanning calorimetry of the luteolin and micronized luteolin (TIFF 2208 kb)

11064_2021_3409_MOESM2_ESM.tiff

Supplementary file2 Supplementary figure 2 Behavioral analysis comparing sham and saline groups in novel tank test. Sham group corresponds to animals manipulated but not exposed to PTZ or drugs and animals from the saline group were pretreated with 0.9% saline, and then exposed to PTZ. Data are expressed as mean ± S.D. Obtained data were analyzed by Welch’s t-test (n = 16) (TIFF 2650 kb)

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Garbinato, C., Lima-Rezende, C.A., Schneider, S.E. et al. Investigation on the Anticonvulsant Potential of Luteolin and Micronized Luteolin in Adult Zebrafish (Danio rerio). Neurochem Res 46, 3025–3034 (2021). https://doi.org/10.1007/s11064-021-03409-8

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