Peripheral olfactory function in rats after chemotherapeutic treatment with the anticancer drug docetaxel
Résumé
Clinical studies have documented that chemotherapeutic cancer treatment in humans is often associated with weight loss and decreased enjoyment of food. Beside taste, olfaction plays a role in the food intake regulation. We assessed whether hemotherapeutic cancer treatment compromises olfactory function in rats treated with docetaxel (Taxotere, TAX), an antineoplastic drug which disrupts the structures necessary for cell survival and division. Electroolfactogram responses (EOG) can indicate morpho-pathological changes in olfactory epithelium. Male rats received either a single, two or three intravenous injections (one per week) of an estimated 10% lethal dose (LD10) of TAX. After a recovery period of 7-9 days the peripheral olfactory function was measured with EOGs from the epithelium overlaying the septum and the turbinates. We tested three different odorants, isoamyl acetate, benzaldehyde and cineole at three different matched recording sites delivered in vapor phase.To assess changes in sensitivity we recorded concentration response curves during days 3-6 after a single drug administration using submergedEOG recording technique allowing a precise control of stimulus concentration. Single, double or triple doses of TAX caused significant attenuation of weight gain over the duration of the experiment. Whatever the duration of the treatment all recording sites were responsive to the three odorants and all stimuli evoked typical EOGs with rapid rising phase and a slower decline. Odorant stimulation as well forskolin and IBXM in the range of 10-6 to 5x10-4 M elicited typical EOG responses in a concentration–dependent manner. Response thresholds and curve shapes were not to be affected by the single treatment. Vapor-phase supraliminal stimulations revealed effects related to the strength of the treatment. Surprisingly,the maximal amplitude of the EOGs for a given odorant and location was greater in rats after two taxotere injections than in untreated animals. The study failed to demonstrate a detrimental effect of taxotere on the peripheral olfactory function in rat. St. Veloso da Silva is supported by a grant from the Ministere de Recherche et Technologie, France.