N-Acetylcysteine Attenuates the Anxiety-Like Behavior and Spatial Cognition Impairment Induced by Doxorubicin and Cyclophosphamide Combination Treatment in Rats
N-Acetylcysteine Attenuates the Anxiety-Like Behavior and Spatial Cognition Impairment Induced by Doxorubicin and Cyclophosphamide Combination Treatment in Rats
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DOI：
10.1159/000512117
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发表时间：
2020-12-22
期刊：
影响因子：
3.1
通讯作者：
Sendo, Toshiaki
中科院分区：
文献类型：
--
作者：
Kitamura, Yoshihisa;Ushio, Soichiro;Sendo, Toshiaki
背景：癌症患者化疗后可出现心理和认知障碍，影响生活质量。目的：氧化应激可能与化疗引起的大鼠心理和认知障碍有关。在本研究中，我们研究了n -乙酰半胱氨酸（一种抗氧化剂）对阿霉素和环磷酰胺联合治疗大鼠的焦虑样行为和认知障碍的影响。方法：大鼠腹腔注射阿霉素和环磷酰胺，每周1次，连续2周。采用明暗测试和新颖的位置识别测试分别评估焦虑样行为和空间认知。采用谷胱甘肽/谷胱甘肽二硫化物定量试剂盒测定大鼠海马谷胱甘肽（GSH）和谷胱甘肽二硫化物（GSSG）水平。结果：阿霉素与环磷酰胺联合用药可引起大鼠焦虑样行为和认知障碍。n -乙酰半胱氨酸逆转了联合治疗诱导的焦虑样行为和新位置识别抑制。此外，阿霉素和环磷酰胺联合用药可显著降低大鼠海马GSH/GSSG比值。n -乙酰半胱氨酸逆转了阿霉素和环磷酰胺处理大鼠GSH/GSSG比值的降低。结论：这些结果提示n -乙酰半胱氨酸通过减少海马氧化应激抑制阿霉素和环磷酰胺诱导的焦虑样行为和认知障碍。
Background: Cancer patients can suffer from psychological and cognitive disorders after chemotherapy, which influence quality of life. Objective: Oxidative stress may contribute to the psychological and cognitive disorders induced in rats by chemotherapy. In the present study, we examined the effects of N-acetylcysteine, an anti-oxidant, on anxiety-like behavior and cognitive impairment in rats treated with a combination of doxorubicin and cyclophosphamide. Methods: Rats were intraperitoneally injected with doxorubicin and cyclophosphamide once a week for 2 weeks. The light-dark test and the novel location recognition test were used to assess anxiety-like behavior and spatial cognition, respectively. The rats' hippocampal levels of glutathione (GSH) and glutathione disulfide (GSSG) were measured using a GSSG/GSH quantification kit. Results: Combined treatment with doxorubicin and cyclophosphamide produced anxiety-like behavior and cognitive impairment in rats. N-acetylcysteine reversed the anxiety-like behavior and inhibition of novel location recognition induced by the combination treatment. Furthermore, the combination of doxorubicin and cyclophosphamide significantly reduced the rats' hippocampal GSH/GSSG ratios. N-acetylcysteine reversed the reduction in the GSH/GSSG ratio seen in the doxorubicin and cyclophosphamide-treated rats. Conclusion: These results suggest that N-acetylcysteine inhibits doxorubicin and cyclophosphamide-induced anxiety-like behavior and cognitive impairment by reducing oxidative stress in the hippocampus.