Laboratory of Neurosciences, Instituto Nacional de Pediatria (INP), Mexico City 04530, Mexico.
Laboratory of Experimental Bacteriology, Instituto Nacional de Pediatria INP, Mexico City 04530, Mexico.
Int J Mol Sci. 2024 Jun 5;25(11):6239. doi: 10.3390/ijms25116239.
Neurotoxicity is a major obstacle in the effectiveness of Cisplatin in cancer chemotherapy. In this process, oxidative stress and inflammation are considered to be the main mechanisms involved in brain and lung toxicity. The aim of the present work was to study the influence of the amount of protein on some oxidative parameters in the brain and lungs of rats treated with Cisplatin (CP) and N-Acetylcysteine (NAC) as neuroprotectors. Four groups of Wistar rats, each containing six animals, were fed with a protein diet at 7% for 15 days. Thereafter, the groups were given either a unique dose of CP 5 mg/kg or NAC 5 mg/kg as follows: group 1 (control), NaCl 0.9% vehicle; group 2, CP; group 3, NAC; and group 4, NAC + CP. The animals were sacrificed immediately after the treatments. Blood samples were collected upon sacrifice and used to measure blood triglycerides and glucose. The brain and lungs of each animal were obtained and used to assay lipid peroxidation (TBARS), glutathione (GSH), serotonin metabolite (5-HIAA), catalase, and the activity of Ca, and Mg ATPase using validated methods. TBARS, HO, and GSH were found to be significantly decreased in the cortex and cerebellum/medulla oblongata of the groups treated with CP and NAC. The total ATPase showed a significant increase in the lung and cerebellum/medulla oblongata, while 5-HIAA showed the same tendency in the cortex of the same group of animals. The increase in 5-HIAA and ATPase during NAC and CP administration resulted in brain protection. This effect could be even more powerful when membrane fluidity is increased, thus proving the efficacy of combined NAC and CP drug therapy, which appears to be a promising strategy for future chemotherapy in malnourished patients.
神经毒性是顺铂在癌症化疗中有效性的主要障碍。在这个过程中,氧化应激和炎症被认为是导致脑和肺毒性的主要机制。本研究旨在研究蛋白质含量对顺铂(CP)和 N-乙酰半胱氨酸(NAC)作为神经保护剂治疗的大鼠大脑和肺部某些氧化参数的影响。将四组 Wistar 大鼠(每组 6 只)用 7%的蛋白质饮食喂养 15 天。此后,各组分别给予唯一剂量的 CP 5mg/kg 或 NAC 5mg/kg,如下:第 1 组(对照组),生理盐水 0.9%载体;第 2 组,CP;第 3 组,NAC;第 4 组,NAC+CP。处理后立即处死动物。处死时采集血样,用于测量血甘油三酯和血糖。从每只动物获得大脑和肺,用于测定脂质过氧化(TBARS)、谷胱甘肽(GSH)、5-羟色胺代谢物(5-HIAA)、过氧化氢酶和 Ca、Mg ATP 酶的活性,使用验证方法。CP 和 NAC 处理组的大脑皮质和小脑/延髓的 TBARS、HO 和 GSH 明显降低。肺和小脑/延髓的总 ATP 酶显著增加,而同一组动物的皮质 5-HIAA 也有相同的趋势。NAC 和 CP 给药时 5-HIAA 和 ATP 酶的增加导致大脑保护。当膜流动性增加时,这种作用可能更加强大,从而证明了联合使用 NAC 和 CP 药物治疗的疗效,这似乎是未来营养不良患者化疗的一种有前途的策略。
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