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.
Departamento Neurologia/Neurocirurgia, Disciplina de Neurologia Experimental, Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil.
Daniele Suzete
DS
Persike
Rodrigo Luiz Oliveira Rodrigues
RL
Cunha
Luiz
L
Juliano
Iara Ribeiro
IR
Silva
Fernanda Elisa
FE
Rosim
Thiago
T
Vignoli
Flavia
F
Dona
Esper Abrão
EA
Cavalheiro
Maria José da Silva
MJ
Fernandes
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