5-HT3 receptor antagonists ameliorate emesis in the ferret evoked by neutron or proton radiation.
BACKGROUND
Nausea and vomiting produced by sub-lethal doses of X- or gamma-rays can be ameliorated by serotonin subtype-three (5-hydroxytryptamine; 5-HT3) receptor antagonists. The effectiveness of these anti-emetics on blocking the emetic responses induced by fission neutron or proton radiation exposure was evaluated in the ferret animal model.


OBJECTIVE
5-HT3 receptor antagonists or bilateral vagotomy will ameliorate that emesis evoked by fission neutrons or protons.


METHODS
Groups of ferrets were exposed to whole-body or head-shielded radiations of varying qualities: fission spectrum neutons, high-energy protons, or gamma-rays. Prior to that exposure, some groups were either vagotomized or received subcutaneous (s.c.) or oral (p.o.) treatment with various doses of the 5-HT3 receptor antagonist antiemetics eusatron and ondansetron.


RESULTS
We demonstrated that both eusatron and ondansetron effectively abolished the emesis normally induced by 2-Gy doses of either 60Co gamma or neutron:gamma, mixed-field irradiation, the latter with a neutron-to-total dose ratio (Dn/Dt) of 0.9+/-2% (%SD). Different routes of delivery of the anti-emetics yielded different degrees of inhibition of the emetic responses; p.o. treatment was less efficacious than s.c. treatment for the emesis to fission neutrons. Eusatron was significantly more effective than ondansetron on a mg x kg(-1) basis. Bilateral vagotomy also attenuated or abolished the emetic responses to the mixed-field neutron exposures. Furthermore, emesis induced by exposure to 2.5 Gy of 200-MeV protons was effectively abolished by ondansetron.


CONCLUSIONS
These results are consistent with the concept that similar physiological and pharmacological mechanisms underlie the emetic responses to different qualities of radiation.
King
G L
GL
Department of Physiology, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA.
Rabin
B M
BM
Weatherspoon
J K
JK
D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005289:Ferrets; D005720:Gamma Rays / Q000009:adverse effects*; D007279:Injections, Subcutaneous; D008297:Male; D009325:Nausea / Q000188:drug therapy* / Q000209:etiology*; D009502:Neutrons / Q000009:adverse effects*; D017294:Ondansetron / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011522:Protons / Q000009:adverse effects*; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D014628:Vagotomy; D014839:Vomiting / Q000188:drug therapy* / Q000209:etiology*; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D011522:Protons; D012702:Serotonin Antagonists; D017294:Ondansetron