Lithium and valproate protect hippocampal slices against ATP-induced cell death.
Lithium and valproate (VPA) are the most commonly prescribed mood-stabilizing drugs. Recently, several studies have reported their neuroprotective properties in several models of neural toxicity and, in some pathological conditions, large amounts of intracellular ATP can be released from damaged cells. In the present study, we investigate the potential neuroprotective effect of lithium and VPA against ATP-induced cell death in hippocampal slices of adult rats. Acute (in vitro) and chronic (in vivo) treatment at therapeutic doses with lithium or VPA significantly prevent the ATP-induced cell death. Lithium and VPA also exerted a synergic effect in the prevention of ATP-induced cell death. Moreover, hippocampal slices prepared from rats chronically treated with lithium or VPA presented a significant reduction in cell death in the presence of cytotoxic extracellular ATP. Although further investigations are necessary, our results show the neuroprotective effect of lithium and VPA against neuronal death induced by extracellular ATP, probably through a different pathway, and suggest novel uses of these drugs in neurogenerative diseases.
Wilot
Leandre Carmen
LC
Departamento de Bioquímica-ICBS, Universidade Federal do Rio Grande do Sul, Av. Ramiro Barcelos, 2600 - anexo, Porto Alegre, RS CEP 90035-003, Brazil.
Bernardi
Andressa
A
Frozza
Rudimar Luiz
RL
Marques
Ana Lucilia
AL
Cimarosti
Helena
H
Salbego
Christianne
C
Rocha
Elizabete
E
Battastini
Ana Maria Oliveira
AM
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000494:pharmacology*
C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D014635:Valproic Acid; D000255:Adenosine Triphosphate; D018021:Lithium Chloride