López-Tofiño Yolanda, Barragán Del Caz Luis Felipe, Benítez-Álvarez David, Molero-Mateo Paula, Nurgali Kulmira, Vera Gema, Bagües Ana, Abalo Raquel
Department of Basic Health Sciences, University Rey Juan Carlos (URJC), Alcorcón, Spain.
High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut), University Rey Juan Carlos (URJC), Alcorcón, Spain.
Front Neurosci. 2023 Dec 18;17:1304609. doi: 10.3389/fnins.2023.1304609. eCollection 2023.
Certain antineoplastic drugs cause gastrointestinal disorders even after the end of treatment. Enteric neuropathy has been associated with some of these alterations. Our goal was to assess the impact of repeated treatment with cisplatin and vincristine on the contractility of circular and longitudinal muscle strips isolated from the rat colon.
Two cohorts of male rats were used: in cohort 1, rats received one intraperitoneal () injection of saline or cisplatin (2 mg kg week) on the first day of weeks 1-5; in cohort 2, rats received two cycles of five daily injections (Monday to Friday, weeks 1-2) of saline or vincristine (0.1 mg kg day). Body weight and food and water intake were monitored throughout the study. One week after treatment, responses of colonic smooth muscle strips to acetylcholine (10-10 M) and electrical field stimulation (EFS, 0.1-20 Hz), before and after atropine (10 M), were evaluated in an organ bath.
Both drugs decreased body weight gain. Compared to saline, cisplatin significantly decreased responses of both longitudinal and circular smooth muscle strips to EFS, whereas vincristine tended to increase them, although in a non-significant manner. No differences were observed in the muscle response to acetylcholine. Atropine abolished the contractile responses induced by acetylcholine, although those induced by EFS were only partially reduced in the presence of atropine.
The findings suggest that although both drugs cause the development of enteric neuropathy, this seems to have a functional impact only in cisplatin-treated animals. Understanding the effects of chemotherapy on gastrointestinal motor function is vital for enhancing the quality of life of cancer patients.
某些抗肿瘤药物即使在治疗结束后仍会导致胃肠道疾病。肠神经病变与其中一些改变有关。我们的目标是评估顺铂和长春新碱重复治疗对从大鼠结肠分离的环形和纵形肌条收缩性的影响。
使用两组雄性大鼠：在第1组中，大鼠在第1 - 5周的第一天接受一次腹腔内（）注射生理盐水或顺铂（2 mg/kg/周）；在第2组中，大鼠接受两个周期的每日五次注射（第1 - 2周，周一至周五）生理盐水或长春新碱（0.1 mg/kg/天）。在整个研究过程中监测体重以及食物和水的摄入量。治疗一周后，在器官浴中评估结肠平滑肌条对乙酰胆碱（10 - 10 M）和电场刺激（EFS，0.1 - 20 Hz）在阿托品（10 M）前后的反应。
两种药物均降低体重增加。与生理盐水相比，顺铂显著降低纵形和环形平滑肌条对EFS的反应，而长春新碱虽有增加趋势，但无统计学意义。在肌肉对乙酰胆碱的反应中未观察到差异。阿托品消除了乙酰胆碱诱导的收缩反应，尽管在阿托品存在下EFS诱导的反应仅部分降低。
研究结果表明，尽管两种药物都会导致肠神经病变的发生，但这似乎仅对接受顺铂治疗的动物有功能影响。了解化疗对胃肠运动功能的影响对于提高癌症患者的生活质量至关重要。
