title: 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.affiliation: Centro de Ciências da Saúde, Laboratório de Bioquímica do Exercício (BioEx), Programa de Pós-Graduação em Farmacologia - Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors.forename: Iuri Domingues
authors.initials: ID
authors.lastname: Della-Pace
authors.forename: Leonardo Magno
authors.initials: LM
authors.lastname: Rambo
authors.forename: Leandro Rodrigo
authors.initials: LR
authors.lastname: Ribeiro
authors.forename: André Luis Lopes
authors.initials: AL
authors.lastname: Saraiva
authors.forename: Sara Marchesan
authors.initials: SM
authors.lastname: de Oliveira
authors.forename: Cássia Regina
authors.initials: CR
authors.lastname: Silva
authors.forename: Jardel Gomes
authors.initials: JG
authors.lastname: Villarinho
authors.forename: Mateus Fortes
authors.initials: MF
authors.lastname: Rossato
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.forename: Leandro M
authors.initials: LM
authors.lastname: de Carvalho
authors.forename: Fernanda
authors.initials: F
authors.lastname: de Oliveira Lima
authors.forename: Ana Flavia
authors.initials: AF
authors.lastname: Furian
authors.forename: Mauro Schneider
authors.initials: MS
authors.lastname: Oliveria
authors.forename: Adair Roberto Soares
authors.initials: AR
authors.lastname: Santos
authors.forename: Valdir A
authors.initials: VA
authors.lastname: Facundo
authors.forename: Michele Rechia
authors.initials: MR
authors.lastname: Fighera
authors.forename: Luiz Fernando Freire
authors.initials: LF
authors.lastname: Royes
mesh_terms: D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010433:Pentylenetetrazole / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D014315:Triterpenes / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D018696:Neuroprotective Agents; D014315:Triterpenes; D000254:Sodium-Potassium-Exchanging ATPase; D010433:Pentylenetetrazole