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在ICR小鼠中,思普拉丁诱导的毒性的日间变化

Sarah Tominaga¹, Hiroki Yoshioka², Tatsuya Hasegawa³

¹Graduate School of Pharmaceutical Sciences, Kinjo Gakuin University, 2-1723 Omori, Moriyamaku, Nagoya, Aichi, 463-8521, Japan; Department of Neurotoxicology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho Mizuho-ku, Nagoya, Aichi, 467-8601, Japan.

Biochemical and biophysical research communications

|June 15, 2024

概括

西斯普拉丁 (CDDP) 治疗时间影响脏毒性. 在小鼠中,在光明期 (ZT2) 中给予CDDP,与黑暗期 (ZT14) 相比,导致显著降低毒性标志物.

科学领域:

药理学药理学是指药理学的学科.
毒理学毒理学毒理学
时间生物学时间生物学

背景情况:

西斯 (CDDP) 是一种重要的基化疗剂,用于治疗各种癌症.
毒性是西斯普拉丁的显著剂量限制副作用.
目前用于减轻西斯普拉丁诱导的毒性策略是不够的.

研究的目的:

调查西斯普拉丁的慢性毒性,探索服用时间作为减少副作用的策略.
评估在光暗周期的不同阶段给药西斯普拉丁对功能和毒性的影响.

主要方法:

雄性ICR小鼠在Zeitgeber时间 (ZT) 2 (光期) 或ZT14 (暗期) 中接受一次腹膜内注射西斯普拉丁 (20 mg/kg).
注射后72小时收集血和脏组织进行分析.
评估的标志物包括体重变化,血血尿素,血肌,脏氧化应激 (甲),DNA损伤 (γH2AX),急性损伤生物标志物 (KIM-1) 和炎症 (Tnfα).

主要成果:

在ZT2和ZT14给药组之间,体重变化是可比的.
当Cisplatin在黑暗阶段 (ZT14) 与光明阶段 (ZT2) 相比,观察到血尿素,血肌,氧化应激,DNA损伤,KIM-1和Tnfα的显著增加.

结论:

西斯普拉丁的服用时间显著影响其毒性.
在轻度阶段 (ZT2) 服用西斯可能会减少对脏的不良影响.
慢性毒理学为优化药物管理时间表提供了有价值的见解,以最大限度地减少毒性并改善患者的治疗结果.

关键词:

时间毒性时间毒性循环节律是循环节律的节奏.西斯普拉丁 (Cisplatin) 是一种毒性毒性毒性副作用副作用副作用副作用

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