Protective effect of the organotelluroxetane RF-07 in pilocarpine-induced status epilepticus.
Temporal lobe epilepsy is the most common form of epilepsy in humans. Caspase activation is a mechanism of cell death induced by seizures. Tellurium (IV) compounds present antitumoral, immunomodulatory and neuroprotective effects due to their ability to inhibit cysteine proteases. We studied the activity of caspase-1, -3 and -8 in the hippocampus of rats exhibiting status epilepticus induced by pilocarpine. All three caspases were activated. Tellurium (IV) compounds RF-07, RF-03 and AS-101 inhibited caspases in vitro, showing high second-order inhibition rate constants. The intraperitoneal injection of RF-07 prior to pilocarpine suppressed the behavioral and electroencephalographic seizure occurrence. According to our results, the caspases are activated as early as 90 min following SE. Tellurium (IV) compounds exerted anticonvulsant effects associated with the inhibition of caspases. These results suggest a promising therapeutic potential of organotellurium (IV) compounds as antiepileptogenic agents.
Persike
Daniele Suzete
DS
Departamento Neurologia/Neurocirurgia, Disciplina de Neurologia Experimental, Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil.
Cunha
Rodrigo Luiz Oliveira Rodrigues
RL
Juliano
Luiz
L
Silva
Iara Ribeiro
IR
Rosim
Fernanda Elisa
FE
Vignoli
Thiago
T
Dona
Flavia
F
Cavalheiro
Esper Abrão
EA
Fernandes
Maria José da Silva
MJ
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D020169:Caspases / Q000187:drug effects* / Q000378:metabolism; D004569:Electroencephalography; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005030:Ethylenes / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D018721:Muscarinic Agonists / Q000633:toxicity; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000201:enzymology*; D013691:Tellurium / Q000494:pharmacology*
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D005030:Ethylenes; D018721:Muscarinic Agonists; D010862:Pilocarpine; C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate; D020169:Caspases; D013691:Tellurium