Antinociceptive properties of diphenyl diselenide: evidences for the mechanism of action.
The present study examined the acute toxicity and antinociceptive effects of diphenyl diselenide (PhSe)2, given orally (p.o.), in chemical and thermical models of pain in mice. Diphenyl diselenide (7.8-312 mg/kg, p.o.) did not cause mortality. This compound did not change plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase) activities as well as urea and creatinine levels in mice after 72 h of exposure. Diphenyl diselenide (1-100 mg/kg, p.o.) inhibited acetic acid-, capsaicin-, glutamate-, bradykinin(BK)- and phorbol myristate acetate (PMA)-induced pain. Diphenyl diselenide also reduced glutamate-, bradykinin-, PMA-induced paw oedema formation. Moreover, diphenyl diselenide caused a significant increase in tail-immersion response latency time. Diphenyl diselenide co-injected subplantarly in association with glutamate-induced a significant reduction of the licking and in the paw oedema formation induced by glutamate. The local pre-treatment of mice with l-arginine, intraplantarly, restored antinociception caused by diphenyl diselenide or N(G)-nitro-L-arginine methyl ester (L-NAME) when analyzed against glutamate-induced nociception. The pre-treatment of mice with dithiothreitol (DTT) intraplantarly restored local antinociception caused by diphenyl diselenide or 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) when analyzed against glutamate-induced nociception. These results indicate that diphenyl diselenide produced antinociception in several models of pain through mechanisms that involve an interaction with not only nitrergic system but also via interaction with redox modulatory sites of glutamate receptors.
Savegnago
Lucielli
L
Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Pinto
Larissa G
LG
Jesse
Cristiano R
CR
Alves
Diego
D
Rocha
Joao B T
JB
Nogueira
Cristina W
CW
Zeni
Gilson
G
D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology* / Q000633:toxicity; D001920:Bradykinin; D002211:Capsaicin; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D005971:Glutamates; D006614:Hindlimb; D006358:Hot Temperature / Q000009:adverse effects; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D016566:Organoselenium Compounds / Q000494:pharmacology* / Q000633:toxicity; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*
D000700:Analgesics; D001555:Benzene Derivatives; D005971:Glutamates; D016566:Organoselenium Compounds; C061132:diphenyldiselenide; D019342:Acetic Acid; D002211:Capsaicin; D001920:Bradykinin