Exploring the neuroprotective potential of antimicrobial peptides from Dinoponera quadriceps venom against pentylenetetrazole-induced seizures in vivo

Epilepsy affects around 50 million people worldwide and 30% of patients have difficulty controlling the disease. The search for substances that can fill the existing gaps in the treatment of epilepsy is of great importance. Arthropod venoms are promising sources for this purpose due to the presence...

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Bibliographic Details
Published in:Toxicon (Oxford) 2024-01, Vol.237, p.107538-107538, Article 107538
Main Authors: Paes, Livia Correia Fernandes, Lima, Dânya Bandeira, Silva, Daniel Moreira Alves da, Valentin, José Tiago, Aquino, Pedro Everson Alexandre de, García-Jareño, Alicia Belén, Orzaéz, Mar, Fonteles, Marta Maria de França, Martins, Alice Maria Costa
Format: Article
Language:English
Subjects:
Animals
Anticonvulsants - pharmacology
Anticonvulsants - therapeutic use
Antimicrobial Peptides
Ants
Arthropod venom
Dinoponera quadriceps
Epilepsy
Humans
Male
Mice
Pentylenetetrazole
Pentylenetetrazole - toxicity
Peptides
Peptides - chemistry
Seizure
Seizures - chemically induced
Seizures - drug therapy
Seizures - prevention & control
Venoms - toxicity
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Summary:Epilepsy affects around 50 million people worldwide and 30% of patients have difficulty controlling the disease. The search for substances that can fill the existing gaps in the treatment of epilepsy is of great importance. Arthropod venoms are promising sources for this purpose due to the presence of small peptides that modulate the activity of ion channels and neuron receptors. The aim of this study was to investigate dinoponeratoxins from the Dinoponera quadriceps ant venom (M-PONTX-Dq3a, M-PONTX-Dq3b and M-PONTX-Dq3c) as potential anticonvulsants. We evaluated them in a seizure model induced by pentylenetetrazole (PTZ) in male swiss mice. Interestingly, intraperitoneal treatment with each peptide increased the time until the first seizure and the percentage of survival, with M-PONTX-Dq3b showing the best results. M-PONTX-Dq3a was discarded due to the appearance of some signs of toxicity with the increase in malondialdehyde (MDA) levels in the striatum. Both, M-PONTX-Dq3b and M-PONTX-Dq3c decreased iNOS and TNF-α in the hippocampus. Notably, M-PONTX-Dq3c treatment decreased the levels of MDA and nitrite in the cortex and hippocampus. Our results indicate that, M-PONTX-Dq3b and M-PONTX-Dq3c have anticonvulsant activity and exhibit anti-inflammatory effects in epilepsy, offering new perspectives for biopharmaceutical development. [Display omitted] •Dinoponeratoxins (DnTxs) are the major component of Dinoponera. quadriceps venom.•D. quadriceps venom has demonstrated the anticonvulsant effect.•DnTxs M-PONTX-Dq3a, -Dq3b and -Dq3c showed anticonvulsant and antioxidant effect.•M-PONTX-Dq3b and -Dq3c decreased iNOS and TNF-α in the hippocampus.•M-PONTX-Dq3b showed the best result and biotechnological potential.
ISSN:0041-0101
1879-3150
DOI:10.1016/j.toxicon.2023.107538