Mogi Keisuke, Azuma Misaki, Iwaki Shiori, Matsuda Yuka, Morito Katsuya, Takayama Kentaro, Nagasawa Kazuki
Laboratory of Environmental Biochemistry, Division of Biological Sciences, Kyoto Pharmaceutical University, 5 Misasaginakauchi-cho, Yamashina-ku, Kyoto 607-8414, Japan.
Chem Senses. 2025 Jan 22;50. doi: 10.1093/chemse/bjaf011.
In cancer chemotherapy, the development of taste disorders is a serious problem because it not only reduces quality of life but also deteriorates patients' nutritional status, sometimes resulting in cessation of chemotherapy. Doxorubicin (DOX), a widely used anticancer anthracycline, reportedly alters patients' taste perception. However, little information exists on the detailed characteristics of DOX-induced taste disorders. In this study, we investigated whether taste responsiveness was altered in DOX-administered mice using a brief-access test and examined the underlying mechanisms. DOX-administered mice exhibited decreased responsiveness to sweet taste, but not to umami, bitter, salty, or sour tastes, on day 7, with recovery by day 14. Although there was no detectable alteration in the number of type II-taste cell marker-immunoreactive cells in the circumvallate papillae (CP), expression of mRNA for sweet taste receptors T1R2, T1R3, and α-gustducin in the CP was greater in DOX-administered mice than in control mice on day 7. Interestingly, in DOX-administered mice on day 7, the lick ratios for a 300-mM sucrose solution showed a significant correlation with the relative expression of T1R3 mRNA in the CP and a trend toward a correlation with food consumption. Together, these findings suggest that the decrease in sweet taste sensitivity in DOX-administered mice might result from dysfunction in signaling downstream of taste perception, with increased sweet taste receptor expression potentially representing a compensatory response to decreased energy intake.
在癌症化疗中，味觉障碍的出现是一个严重问题，因为它不仅会降低生活质量，还会使患者的营养状况恶化，有时甚至导致化疗中断。阿霉素（DOX）是一种广泛使用的抗癌蒽环类药物，据报道会改变患者的味觉感知。然而，关于DOX诱导的味觉障碍的详细特征的信息却很少。在本研究中，我们使用短期接触试验研究了给予DOX的小鼠的味觉反应是否发生改变，并探讨了其潜在机制。给予DOX的小鼠在第7天对甜味的反应性降低，但对鲜味、苦味、咸味或酸味的反应性未降低，到第14天恢复。尽管在轮廓乳头（CP）中II型味觉细胞标记免疫反应性细胞的数量没有可检测到的变化，但在第7天，给予DOX的小鼠CP中甜味受体T1R2、T1R3和α-味导素的mRNA表达高于对照小鼠。有趣的是，在第7天给予DOX的小鼠中，300 mM蔗糖溶液的舔舐比率与CP中T1R3 mRNA的相对表达呈显著相关，并且与食物摄入量有相关趋势。这些发现共同表明，给予DOX的小鼠甜味敏感性降低可能是由于味觉感知下游信号传导功能障碍所致，甜味受体表达增加可能代表对能量摄入减少的一种代偿反应。
