Yanagawa Hiroto, Koyama Yoshihisa, Kobayashi Yuki, Kobayashi Hikaru, Shimada Shoichi
Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan.
Addiction Research Unit, Osaka Psychiatric Research Center, Osaka Psychiatric Medical Center, Osaka, 541-8567, Japan.
Biochem Biophys Rep. 2022 Oct 8;32:101363. doi: 10.1016/j.bbrep.2022.101363. eCollection 2022 Dec.
Anticancer agents can effectively treat several types of cancers but are often limited in clinical settings due to various adverse effects. In particular, nausea and vomiting are serious side effects that markedly reduce the patients' quality of life. Accordingly, the development of novel antiemetic drugs that lack side effects is crucial, given that most conventional antiemetic drugs are known to possess side effects. In addition, reactive oxygen species generated by anticancer agents are involved in nausea and vomiting; hence, appropriate antioxidants might also be effective toward nausea and vomiting. Silicon (Si)-based agents can abundantly generate antioxidant hydrogen in the intestine. Therefore, we assessed whether Si-based agents could be effective against nausea associated with anticancer agents in cisplatin-injected mice. We observed numerous neurons expressing c-Fos protein, a neuronal activity marker, in the nausea-associated regions of the dorsal medulla (area postrema, nuclei of the solitary tract, and dorsal vagal nuclei) 24 h after cisplatin injection. Conversely, mice fed a diet containing 2.5% Si-based agents showed a reduction in c-Fos-positive neurons. These findings revealed that the Si-based agent alleviated cisplatin-induced nausea. Si-based agents demonstrate potent antioxidant effects by producing hydrogen, which has no known side effects and will be a safer antiemetic agent and greatly help improve the quality of life of patients undergoing anticancer drug treatment.
抗癌药物可以有效治疗多种类型的癌症,但由于各种不良反应,在临床应用中常常受到限制。特别是恶心和呕吐是严重的副作用,会显著降低患者的生活质量。因此,鉴于大多数传统止吐药物都已知存在副作用,开发无副作用的新型止吐药物至关重要。此外,抗癌药物产生的活性氧参与恶心和呕吐的发生;因此,合适的抗氧化剂可能对恶心和呕吐也有效。硅基制剂可以在肠道中大量产生抗氧化剂氢气。因此,我们评估了硅基制剂是否能有效对抗顺铂注射小鼠中与抗癌药物相关的恶心。在顺铂注射24小时后,我们观察到在延髓背侧与恶心相关的区域(最后区、孤束核和迷迷束旁核)有大量表达神经元活动标记物c-Fos蛋白的神经元。相反,喂食含2.5%硅基制剂饮食的小鼠中c-Fos阳性神经元减少。这些发现表明硅基制剂减轻了顺铂诱导的恶心。硅基制剂通过产生氢气表现出强大的抗氧化作用,氢气没有已知的副作用,将是一种更安全的止吐药物,并将极大地有助于提高接受抗癌药物治疗患者的生活质量。