Peripheral olfactory sensitivity in rodents after treatment with docetaxel.
OBJECTIVE
Clinical studies have documented that cytotoxic chemotherapy is often associated with body weight loss and decreased enjoyment of food. Besides taste, olfaction plays a role in food intake. We assessed whether systemic chemotherapeutic cancer treatment compromises olfactory function in rats and mice treated with docetaxel (Taxotere; Sanofi-Aventis, Paris, France).


METHODS
Randomized, controlled trials on mice and rats.


METHODS
Male mice received a single and male rats either a single, two, or three docetaxel administrations. Olfactory function was tested by means of electroolfactograms (EOGs) from the chemosensory epithelium of the nasal septum and the endoturbinates. We evaluated and compared the magnitude of EOG responses evoked by different odorants recorded at different time points after treatment.


RESULTS
In both animal species, docetaxel administration reduced body weight gain, thus evidencing the general toxic effect of the drug. In both animal species, the olfactory mucosa remained responsive to stimulation of odorants during the whole course of experiment, but treatment revealed regional differences of docetaxel susceptibility and induced marked transitory electrophysiological changes. In mice and rats a significant transitory decrease in EOG response magnitude occurred after a single administration. Unexpectedly, in rats we also observed an increase of the olfactory response following the second administration of the drug.


CONCLUSIONS
Docetaxel exerts a neurotoxic effect on olfactory epithelia of rodents at doses similar to human doses, thus inducing transitory functional alterations. Although moderate, they are consistent with the hypothesis of a dysfunction of olfactory function. Further experiments are needed to elucidate the origin of the electrophysiological effects and their impact on the olfactory perception.
Faure
Frédéric
F
Department of Otolaryngology, Head and Neck Surgery, Hôpital Edouard Herriot, Lyon, Dijon, France.
Da Silva
Stéphanie Veloso
SV
Jakob
Ingrid
I
Pasquis
Bruno
B
Sicard
Gilles
G
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D055724:Electrophysiological Phenomena; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D009831:Olfactory Mucosa / Q000187:drug effects / Q000294:innervation; D009833:Olfactory Pathways / Q000187:drug effects / Q000503:physiopathology*; D055696:Olfactory Perception / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D043823:Taxoids; D000077143:Docetaxel