Anti-emetic effect of ondansetron and granisetron after exposure to mixed neutron and gamma irradiation.
The anti-emetic efficiency of orally administered ondansetron and granisetron has been tested in macaques exposed to a mixed y and neutron radiation (6 Gy) with a high neutron/gamma-ray ratio. Our experiments reveal that a single delivery of ondansetron (1 or 2 mg kg(-1)) or of granisetron (0.25 mg kg(-1)) 45-90 min before irradiation or 35-45 min after irradiation was not totally effective. Conversely, the delivery of two doses with the same delay prior to and after exposure led to a complete prevention of vomiting and retching. These observations can be explained by the dual mechanism of radiation-induced emesis: an early peripheral mechanism and a later central mechanism. Two deliveries of 5-HT3 receptor antagonists seem to disrupt serotonergic transmission at the brain stem structures and to affect the peripheral release of serotonin from the gut, thus completely preventing radiation-induced vomiting. This study confirms that the 5-HT3-dependent mechanisms that mediate emesis are similar for both neutron and gamma radiation.
Martin
C
C
Département de Radiobiologie, Centre de Recherches du Service de Santé des Armées Emile Parde, La Tronche, France.
Roman
V
V
Agay
D
D
Fatôme
M
M
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D005720:Gamma Rays; D017829:Granisetron / Q000494:pharmacology*; D008252:Macaca fascicularis; D008297:Male; D009325:Nausea / Q000209:etiology / Q000517:prevention & control*; D009502:Neutrons; D017294:Ondansetron / Q000494:pharmacology*; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000517:prevention & control*; D011985:Receptors, Serotonin / Q000502:physiology; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014839:Vomiting / Q000209:etiology / Q000517:prevention & control*
D000932:Antiemetics; D017829:Granisetron; D017294:Ondansetron; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists