Diphenyl diselenide and 2,3-dimercaptopropanol increase the PTZ-induced chemical seizure and mortality in mice.
The aim of the present study was to evaluate the interaction between a classic GABAergic antagonist -- pentylenetetrazol (PTZ) with an organoselenium compound -- diphenyl diselenide (PhSe)(2) and with the metal chelating agent -- 2,3 dimercaptopropanol (BAL). Mice were pre-treated with 150 micromol/kg (PhSe)(2) or BAL (250, 500 or 1000 micromol/kg) before treatment with PTZ. Pre-treatment with (PhSe)(2) reduced the latency for PTZ-induced seizure at doses of 40 and 60 mg/kg and cause a decrease in the latency for PTZ-induced death at the dose of 60 mg/kg. However, treatment with PTZ at dose of 80 mg/kg was not affected by (PhSe)(2) pre-treatment. Pre-treatment with BAL reduced the latency for PTZ-induced seizure at doses of 40 and 50 mg/kg. In addition, the latency for PTZ-induced death at the dose of 40 mg/kg was decreased significantly by pre-treatment with all doses of BAL. At the dose of 50mg/kg, a significant decrease in the latency for death occurred only in mice pre-treated with 500 and 1000 micromol/kg of BAL. Our results indicate that the PTZ-induced chemical seizures and mortality was enhanced by (PhSe)(2) and BAL. These results indicated that (PhSe)(2) and BAL interact with PTZ possibly by modulating the GABAergic system.
Brito
Verônica B
VB
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CAMPUS UNIVERSITRAIO-CAMOBI, 97105-900 Santa Maria, RS, Brazil.
Folmer
Vanderlei
V
Puntel
Gustavo O
GO
Fachinetto
Roselei
R
Soares
Júlio C M
JC
Zeni
Gilson
G
Nogueira
Cristina W
CW
Rocha
João B T
JB
D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002614:Chelating Agents / Q000633:toxicity; D003292:Convulsants / Q000633:toxicity*; D004112:Dimercaprol / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018756:GABA Antagonists / Q000633:toxicity; D008297:Male; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D016566:Organoselenium Compounds / Q000633:toxicity*; D010433:Pentylenetetrazole / Q000633:toxicity*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D015996:Survival Rate; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001555:Benzene Derivatives; D002614:Chelating Agents; D003292:Convulsants; D018756:GABA Antagonists; D016566:Organoselenium Compounds; D018079:Receptors, GABA; D004112:Dimercaprol; C061132:diphenyldiselenide; D005680:gamma-Aminobutyric Acid; D010433:Pentylenetetrazole