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

Abstract

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 GABA(A) receptor antagonist PTZ (80 g; i.p.). The TTHL pretreatment also protected against PTZ-induced deleterious effects, as characterized by protein carbonylation, lipid peroxidation, [(3)H] glutamate uptake and the inhibition of Na(+),K(+)-ATPase (subunits α(1) and α(2)/α(3)). Although TTHL did not exhibit DPPH, ABTS radical scavenging activity per se and does not alter the binding of [(3)H]flunitrazepam to the benzodiazepinic site of the GABA(A) 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.

• Authors: Iuri Domingues Della-Pace, Leonardo Magno Rambo, Leandro Rodrigo Ribeiro, André Luis Lopes Saraiva, Sara Marchesan de Oliveira, Cássia Regina Silva, Jardel Gomes Villarinho, Mateus Fortes Rossato, Juliano Ferreira, Leandro M de Carvalho, Fernanda de Oliveira Lima, Ana Flavia Furian, Mauro Schneider Oliveria, Adair Roberto Soares Santos, Valdir A Facundo, Michele Rechia Fighera, Luiz Fernando Freire Royes
• Journal: Neuropharmacology (Neuropharmacology) Vol. 67 Pg. 455-64 (Apr 2013) ISSN: 1873-7064 [Electronic] England
• PMID: 23219656 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Neuroprotective Agents
• Triterpenes
• Sodium-Potassium-Exchanging ATPase
• Pentylenetetrazole

Topics

• Animals
• Enzyme Activation (drug effects, physiology)
• Injections, Intraventricular
• Mice
• Neuroprotective Agents (administration & dosage, chemistry)
• Oxidative Stress (drug effects, physiology)
• Pentylenetetrazole (toxicity)
• Seizures (chemically induced, enzymology, prevention & control)
• Sodium-Potassium-Exchanging ATPase (physiology)
• Triterpenes (administration & dosage, chemistry)