title: Oxaliplatin Alters Expression of T1R2 Receptor and Sensitivity to Sweet Taste in Rats.
abstract: As one of the adverse effects of oxaliplatin, a key agent in colon cancer chemotherapy, a taste disorder is a severe issue in a clinical situation because it decreases the quality of life of patients. However, there is little information on the mechanism underlying the oxaliplatin-induced taste disorder. Here, we examined the molecular and behavioral characteristics of the oxaliplatin-induced taste disorder in rats. Oxaliplatin (4-16 mg/kg) was administered to Sprague-Dawley (SD) rats intraperitoneally for 2 d. Expression levels of mRNA and protein of taste receptors in circumvallate papillae (CP) were measured by real-time quantitative polymerase chain reaction (PCR) and immunohistochemistry, respectively. Taste sensitivity was assessed by their behavioral change using a brief-access test. Morphological change of the taste buds in CP was evaluated by hematoxyline-eosin (HE) staining, and the number of taste cells in taste buds was counted by immunohistochemical analysis. Among taste receptors, the expression levels of mRNA and protein of T1R2, a sweet taste receptor subunit, were increased transiently in CP of oxaliplatin-administered rats on day 7. In a brief-access test, the lick ratio was decreased in oxaliplatin-administered rats on day 7 and the alteration was recovered to the control level on day 14. There was no detectable alteration in the morphology of taste buds, number of taste cells or plasma zinc level in oxaliplatin-administered rats. These results suggest that decreased sensitivity to sweet taste in oxaliplatin-administered rats is due, at least in part, to increased expression of T1R2, while these alterations are reversible.
authors.affiliation: Department of Environmental Biochemistry, Kyoto Pharmaceutical University.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohishi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nishida
authors.forename: Yuri
authors.initials: Y
authors.lastname: Yamanaka
authors.forename: Ai
authors.initials: A
authors.lastname: Miyata
authors.forename: Akiko
authors.initials: A
authors.lastname: Ikukawa
authors.forename: Miharu
authors.initials: M
authors.lastname: Yabu
authors.forename: Karin
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Saho
authors.initials: S
authors.lastname: Bansho
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nagasawa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D008297:Male; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077150:Oxaliplatin; D010984:Platinum / Q000097:blood / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism; D013649:Taste / Q000187:drug effects*; D013650:Taste Buds / Q000033:anatomy & histology / Q000187:drug effects; D013651:Taste Disorders / Q000139:chemically induced / Q000378:metabolism*; D014059:Tongue / Q000187:drug effects / Q000378:metabolism; D015032:Zinc / Q000097:blood / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D000077150:Oxaliplatin; D010984:Platinum; D015032:Zinc