Possible peripheral mechanism for taste disorder in rats administered S-1

• Published in: International journal of clinical oncology 2014-06, Vol.19 (3), p.549-556
• Main Authors: Aoki, Kumiko, Obata, Koji, Kurihara, Miyako, Kuniyasu, Hiroki, Kirita, Tadaaki, Takaki, Miyako
• Format: Article
• Language: English
• Subjects: Animals; Cancer; Cancer Research; Cancer therapies; Drug Combinations; Ganglia - drug effects; Male; Medicine; Medicine & Public Health; Nerve Degeneration - chemically induced; Nerve Endings - drug effects; Nerve Endings - pathology; Oncology; Original Article; Oxonic Acid - adverse effects; Quinine; Rats, Wistar; Side effects; Surgical Oncology; Taste; Taste Buds - drug effects; Taste Disorders - chemically induced; Tegafur - adverse effects; Tongue - drug effects; Tongue - pathology
• ISSN: 1341-9625; 1437-7772
• DOI: 10.1007/s10147-013-0572-3

Background Taste disorders are frequently observed in cancer patients undergoing chemotherapy and are serious adverse events which impair the quality of life (QoL) of the cancer patient. Nevertheless, taste disorder mechanisms in cancer patients undergoing chemotherapy have not yet been fully elucidated. The aim of this study was to reveal taste disorder-related peripheral mechanisms using the two-bottle preference test (TBPT) and histological examination of tongues by hematoxylin–eosin staining and immunohistochemistry with protein-gene product 9.5. Methods In the TBPT, one bottle was filled with the 0.01 mM quinine hydrochloride (quinine), as a bitter compound, and the other was filled with water. Doses of 50 and 100 mg kg −1  day −1 S-1 (tegafur/gimeracil/oteracil potassium) are lethal to Wistar rats. Therefore, doses ranging from 2–20 mg kg −1  day −1 were administered to the rats for 3 weeks. The S-1 dose of 2 mg kg −1  day −1 corresponds to the clinical dose administered to cancer patients. The part of the tongue containing the circumvallate papillae was excised the following TBPT. Results The rate of increase in terms of the average preference rate for the quinine vs. all intake (quinine plus water) was significant from the initial S-1 period to the final one, compared with that in control rats, suggesting the possibility of a worsening sensation for the bitter taste. In S-1 rats, the area of taste nerve fibers were significantly decreased and the rate of degeneration of intra-tongue ganglionic nerve cells was significantly increased. These changes were significantly correlated with the rate of increase in average preference rate of the quinine. Conclusion Neuropathy of the gustatory nerve at the periphery may be involved in taste disorders induced by an anticancer drug.