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Berberine and hesperidin prevent the memory consolidation impairment induced by pentylenotetrazole in zebrafish.

This study verified the effects of the natural compounds berberine and hesperidin on seizure development and cognitive impairment triggered by pentylenetetrazole (PTZ) in zebrafish. Adult animals were submitted to a training session in the inhibitory avoidance test and, after 10minutes, they received an intraperitoneal injection of 25, 50, or 100mg/kg berberine or 100 or 200mg/kg hesperidin. After 30minutes, the animals were exposed to 7.5mM PTZ for 10minutes. Animals were submitted to the test session 24h after the training session to verify their cognitive performance. Zebrafish larvae were exposed to 100µM or 500µM berberine or 10µM or 50µM hesperidin for 30minutes. After, larvae were exposed to PTZ and had the seizure development evaluated by latency to reach the seizure stages I, II, and III. Adult zebrafish pretreated with 50mg/kg berberine showed a longer latency to reach stage III. Zebrafish larvae pretreated with 500µM berberine showed a longer latency to reach stages II and III. Hesperidin did not show any effect on seizure development both in larvae and adult zebrafish. Berberine and hesperidin pretreatments prevented the memory consolidation impairment provoked by PTZ-induced seizures. There were no changes in the distance traveled in adult zebrafish pretreated with berberine or hesperidin. In larval stage, berberine caused no changes in the distance traveled; however, hesperidin increased the locomotion. Our results reinforce the need for investigating new therapeutic alternatives for epilepsy and its comorbidities.

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