Aoki Kumiko, Obata Koji, Kurihara Miyako, Kuniyasu Hiroki, Kirita Tadaaki, Takaki Miyako
Department of Physiology II, Nara Medical University, School of Medicine, 840 Shijo-cho, Kashihara, 634-8521, Japan.
Int J Clin Oncol. 2014;19(3):549-56. doi: 10.1007/s10147-013-0572-3. Epub 2013 Jun 4.
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.
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.
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.
Neuropathy of the gustatory nerve at the periphery may be involved in taste disorders induced by an anticancer drug.
味觉障碍在接受化疗的癌症患者中经常出现，是严重的不良事件，会损害癌症患者的生活质量（QoL）。然而，化疗癌症患者味觉障碍的机制尚未完全阐明。本研究的目的是通过双瓶偏好试验（TBPT）以及苏木精-伊红染色和蛋白基因产物9.5免疫组织化学对舌头进行组织学检查，揭示与味觉障碍相关的外周机制。
在TBPT中，一个瓶子装有作为苦味化合物的0.01 mM盐酸奎宁，另一个装有水。50和100 mg kg(-1) day(-1) 的替吉奥（替加氟/吉美嘧啶/奥替拉西钾）剂量对Wistar大鼠具有致死性。因此，给大鼠施用2 - 20 mg kg(-1) day(-1) 的剂量，持续3周。2 mg kg(-1) day(-1) 的替吉奥剂量相当于给予癌症患者的临床剂量。在进行TBPT后，切除含有轮廓乳头的舌部组织。
与对照大鼠相比，从最初的替吉奥给药期到最后一期，奎宁相对于所有摄入量（奎宁加水）的平均偏好率增加率显著升高，这表明苦味感觉可能恶化。在替吉奥处理的大鼠中，味觉神经纤维面积显著减少，舌内神经节神经细胞的退化率显著增加。这些变化与奎宁平均偏好率的增加率显著相关。
外周味觉神经病变可能与抗癌药物引起的味觉障碍有关。
