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氨磷汀对顺铂诱导的大鼠脑损伤中凋亡炎症标志物的影响。

Effect of amifostine on apoptotic inflammatory makers in cisplatin induced brain damage in rats.

作者信息

Masoud Mahmoud M, El-Laithy Nabila A, Youness Eman R, Ahmed Nadia M, Mahdy Elsayed M E, Shousha Wafaa Gh

机构信息

68787 Medical Biochemistry Department, Medical Research and Clinical Studies Institute - National Research Centre , Cairo, Egypt.

Department of Chemistry, Faculty of Science, Helwan University, Helwan, Egypt.

出版信息

J Complement Integr Med. 2025 Feb 3. doi: 10.1515/jcim-2024-0250.

DOI:10.1515/jcim-2024-0250
PMID:39889275
Abstract

OBJECTIVES

To lessen the negative effects of the medication, we assessed the neuroprotective impact of amifostine nanoparticles against the neurotoxicity generated by cisplatin.

METHODS

60 adult male albino Wistar rats were arranged into six groups. Group 1; received saline intraperitonealy (IP) and served as negative control. Group 2; received IP injection of silica nano-emulsion, Group 3 received cispatin for three consecutive days at the end of the study, Group 4 received amifostine intrapretonealy (IP) before cisplatin injection, Group 5 received silica nano-emulsion alone for one month, group 6 received silica nano-emulsion in combination with cisplatin for three consecutive days at the end of the study. Monocyte chemoattractant protein-1 (MCP-1) and glial fibrillary acidic protein (GFAP) were estimated by ELISA, butrylcholinesterase (BChE) by spectrophotometric method while caspase-3 as a marker of apoptosis by PCR.

RESULTS

The mean levels of brain GFAP, MCP-1, and caspase-3 in the cisplatin group were considerably higher than those in the control group. However, there was a drop in the average level of brain BChE activity. Additionally, the injection of (SiNPs@AMF + cisplatin) increased BChE activities while reducing GFAP, MCP-1, and caspase-3 levels, thereby reversing the negative effects of cisplatin on the brain tissue. On the other hand, the group treated with SiNPs@AMF + cisplatin showed improvement in overall brain structure and minimal pyknotic nuclei and apoptotic neurons were found.

CONCLUSIONS

These outcomes demonstrated amifostine's ability to lessen the histological changes brought on by cisplatin. To sum up, SiNPs@AMF may be a suitable and secure supplemental treatment agent to lessen cisplatin's toxicity in the brain and enhance the treatment's effects throughout chemotherapy.

摘要

目的

为减轻药物的负面影响,我们评估了氨磷汀纳米颗粒对顺铂所致神经毒性的神经保护作用。

方法

将60只成年雄性白化Wistar大鼠分为六组。第1组腹腔注射生理盐水作为阴性对照;第2组腹腔注射二氧化硅纳米乳剂;第3组在研究结束时连续三天接受顺铂注射;第4组在注射顺铂前腹腔注射氨磷汀;第5组单独接受二氧化硅纳米乳剂治疗一个月;第6组在研究结束时连续三天接受二氧化硅纳米乳剂与顺铂联合治疗。采用酶联免疫吸附测定法(ELISA)检测单核细胞趋化蛋白-1(MCP-1)和胶质纤维酸性蛋白(GFAP),用分光光度法检测丁酰胆碱酯酶(BChE),通过聚合酶链反应(PCR)检测凋亡标志物半胱天冬酶-3(caspase-3)。

结果

顺铂组脑GFAP、MCP-1和caspase-3的平均水平显著高于对照组。然而,脑BChE活性的平均水平有所下降。此外,注射(二氧化硅纳米颗粒@氨磷汀+顺铂)可增加BChE活性,同时降低GFAP、MCP-1和caspase-3水平,从而逆转顺铂对脑组织的负面影响。另一方面,接受二氧化硅纳米颗粒@氨磷汀+顺铂治疗的组脑整体结构有所改善,发现的固缩核和凋亡神经元最少。

结论

这些结果表明氨磷汀能够减轻顺铂引起的组织学变化。总之,二氧化硅纳米颗粒@氨磷汀可能是一种合适且安全的辅助治疗药物,可减轻顺铂在脑中的毒性,并在整个化疗过程中增强治疗效果。

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