Mechanisms involved in the antinociceptive and anti-inflammatory effects of bis selenide in mice.
OBJECTIVE
The present study examined the mechanisms involved in the antinociceptive effects of bis selenide [(Z)-2,3-bis(4-chlorophenylselanyl)prop-2-en-1-ol].


METHODS
The effects of oral bis selenide were tested against licking behaviour and oedema in mice induced by formalin, serotonin, histamine, glutamate, phorbol 12-myristate 13-acetate (PMA), 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) and prostaglandin E2. The effects of a variety of receptor antagonists on the antinociceptive activity were tested to determine the likely mechanism of action of bis selenide.


RESULTS
Bis selenide caused antinociception on the first and second phases of the formalin test, with mean ID50 values of 34.21 (29.66-39.45) and 15.86 (12.17-20.67) mg/kg and maximal inhibition of 65+/-3% and 90+/-1%, respectively. At 50 mg/kg bis selenide significantly inhibited (31+/-2%) paw oedema induced by intraplantar injection of formalin. At 25 mg/kg given 5 min after the formalin injection, bis selenide caused a significant inhibition (42+/-5%) in the second phase of the formalin test, whereas the prophylactic treatment caused more intense inhibition (64+/-3%). Oral administration of bis selenide reduced licking and paw oedema induced by serotonin, histamine, glutamate, PGE2, PMA and 8-BrcAMP. The antinociceptive effect of bis selenide (25 mg/kg, p.o.) on the formalin test was reversed by i.p. administration of p-chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis), ketanserin (a selective 5-HT2A receptor antagonist), ondansetron (a 5-HT3 receptor antagonist) and ranitidine (a histamine H2-receptor antagonist).


CONCLUSIONS
Glutamatergic, prostaglandin E2, serotonergic (5-HT2A and 5-HT3) and histamine H2 receptors are involved in the antinociceptive effects of bis selenide in mice. The interaction of bis selenide with protein kinase C and A signalling pathways was also demonstrated.
Jesse
Cristiano R
CR
Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Brazil.
Savegnago
Lucielli
L
Nogueira
Cristina W
CW
D000284:Administration, Oral; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D008297:Male; D051379:Mice; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010147:Pain Measurement / Q000379:methods; D011493:Protein Kinase C / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology; D018078:Receptors, Prostaglandin E / Q000502:physiology; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology; D015398:Signal Transduction
C533977:(Z)-2,3-bis(4-chlorophenylselanyl)prop-2-en-1-ol; D000700:Analgesics; D016566:Organoselenium Compounds; D044402:Receptor, Serotonin, 5-HT2A; D017470:Receptors, Glutamate; D011970:Receptors, Histamine H2; D018078:Receptors, Prostaglandin E; D044406:Receptors, Serotonin, 5-HT3; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C