Triterpene 3β, 6β, 16β trihidroxilup-20(29)-ene protects against excitability and oxidative damage induced by pentylenetetrazol: The role of Na+,K+-ATPase activity

Administration of the compound triterpene 3β, 6β, 16β-trihidroxilup-20(29)-ene (TTHL) resulted in antinociceptive activity in several pain models in mice. Because pain and epilepsy have common mechanisms, and several anticonvulsants are clinically used to treat painful disorders, we investigated the...

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Published in:Neuropharmacology 2013-04, Vol.67, p.455-464
Main Authors: Della-Pace, Iuri Domingues, Rambo, Leonardo Magno, Ribeiro, Leandro Rodrigo, Saraiva, André Luis Lopes, de Oliveira, Sara Marchesan, Silva, Cássia Regina, Villarinho, Jardel Gomes, Rossato, Mateus Fortes, Ferreira, Juliano, de Carvalho, Leandro M., de Oliveira Lima, Fernanda, Furian, Ana Flavia, Oliveria, Mauro Schneider, Santos, Adair Roberto Soares, Facundo, Valdir A., Fighera, Michele Rechia, Royes, Luiz Fernando Freire
Format: Article
Language:English
Subjects:
Animals
Enzyme Activation - drug effects
Enzyme Activation - physiology
Injections, Intraventricular
Mice
Na+,K+-ATPase
Neuroprotective Agents - administration & dosage
Neuroprotective Agents - chemistry
Ouabain
Oxidative damage
Oxidative Stress - drug effects
Oxidative Stress - physiology
Pentylenetetrazol
Pentylenetetrazole - toxicity
Seizures
Seizures - chemically induced
Seizures - enzymology
Seizures - prevention & control
Sodium-Potassium-Exchanging ATPase - physiology
Triterpene
Triterpenes - administration & dosage
Triterpenes - chemistry
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Summary:Administration of the compound triterpene 3β, 6β, 16β-trihidroxilup-20(29)-ene (TTHL) resulted in antinociceptive activity in several pain models in mice. Because pain and epilepsy have common mechanisms, and several anticonvulsants are clinically used to treat painful disorders, we investigated the anticonvulsant potential of TTHL. Behavioral and electrographic recordings revealed that pretreatment with TTHL (30 mg/kg; i.g.) increased the latencies to the first clonic seizure to the tonic–clonic and reduced the duration of the generalized seizures induced by the GABAA receptor antagonist PTZ (80 g; i.p.). The TTHL pretreatment also protected against PTZ-induced deleterious effects, as characterized by protein carbonylation, lipid peroxidation, [3H] glutamate uptake and the inhibition of Na+,K+-ATPase (subunits α1 and α2/α3). Although TTHL did not exhibit DPPH, ABTS radical scavenging activity per se and does not alter the binding of [3H]flunitrazepam to the benzodiazepinic site of the GABAA receptor, this compound was effective in preventing behavioral and EEG seizures, as well as the inhibition of Na+,K+-ATPase induced by ouabain. These results suggest that the protection against PTZ-induced seizures elicited by TTHL is due to Na+,K+-ATPase activity maintenance. In fact, experiments in homogenates of the cerebral cortex revealed that PTZ (10 mM) reduced Na+,K+-ATPase activity and that previous incubation with TTHL (10 μM) protected against this inhibition. Collectively, these data indicate that the protection exerted by TTHL in this model of convulsion is not related to antioxidant activity or GABAergic activity. However, these results demonstrated that the effective protection of Na+,K+-ATPase elicited by this compound protects against the damage due to neuronal excitability and oxidation that is induced by PTZ. In the present study we revealed that previous administration of TTHL protected against the seizures induced by the GABAA receptor antagonist PTZ ▪. TTHL pretreatment also protected against PTZ-induced deleterious effects, characterized here by reactive oxygen species (ROS), [3H] glutamate uptake and Na+,K+-ATPase inhibition (subunits α1 and α2/α3) ▪. Although TTHL has no antioxidant activity per se and not alter the [3H]flunitrazepam binding to benzodiazepinic site of GABAA receptors and Glutamate, ▪ this triterpene protected against the seizures induced by Na+,K+-ATPase inhibitor (ouabain). These results suggest that effective protection of se
ISSN:0028-3908
1873-7064
DOI:10.1016/j.neuropharm.2012.10.022