Role of bone marrow mesenchymal stem cell-derived exosomes in reducing neurotoxicity and depression-like behaviors induced by doxorubicin in rats.

IF 2.2 4区 医学 Q3 TOXICOLOGY Toxicology Research Pub Date : 2024-10-03 eCollection Date: 2024-10-01 DOI:10.1093/toxres/tfae159
Doaa R I Abdel-Gawad, Fatma Khalil, Olfat Shehata, Marwa A Ibrahim, SalmaI El-Samannoudy, Emad A Mahdi, Nema S Shaban
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Abstract

Background: Doxorubicin (DOX) is a broad-spectrum antitumor drug while its use is limited nowadays due to its neurobiological side effects associated with depression. Bone marrow mesenchymal stem cells (BM-MSCs) derived exosomes are a promising regenerative therapy. In this study, we investigated the therapeutic potentiality of BM-MSCs derived exosomes against the neurotoxicity induced by DOX.

Methods: Twenty-four male albino rats were divided equally in to three groups as follow: group 1 (control), group 2 (rats injected intraperitoneally (i.p|) with DOX at a dose 2.5mg/Kg), and group 3 (rats injected with DOX and BM-MSCs derived exosomes i.p at a dose 1.5ml/Kg). During the experiment the behavior tests were noted, after three weeks rats were sacrificed, serum and brain samples were collected for biochemical, molecular and histopathological examinations.

Results: The results revealed that DOX causing impairment of the locomotor and increasing the anxiety like behavior of rats, marked neuropathological changes, significant elevation of MDA content and TNF-α concentration, reduction of phospholipase (PLD) and acetylcholinesterase (AChE) protein concentration in addition, there were up regulation of JNK, NF-κB and p38 genes and down regulation of Erk1.

Conclusion: Exosomal therapy improved the substantial neurotoxicity of DOX through modulating the markers involved in the neurotoxic signalling pathway of DOX that resulting in improving the pathological lesions and the animal behaviours.

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骨髓间充质干细胞衍生的外泌体在减少多柔比星诱导的大鼠神经毒性和抑郁样行为中的作用
背景:多柔比星(DOX)是一种广谱抗肿瘤药物,但由于其与抑郁症相关的神经生物学副作用,如今其使用已受到限制。骨髓间充质干细胞(BM-MSCs)衍生的外泌体是一种很有前景的再生疗法。在这项研究中,我们探讨了骨髓间充质干细胞衍生的外泌体对DOX诱导的神经毒性的治疗潜力:将 24 只雄性白化大鼠平均分为以下三组:第 1 组(对照组)、第 2 组(腹腔注射 DOX,剂量为 2.5 毫克/千克)和第 3 组(腹腔注射 DOX 和 BM-MSCs 派生外泌体,剂量为 1.5 毫升/千克)。实验期间对大鼠进行行为测试,三周后将大鼠处死,采集血清和脑样本进行生化、分子和组织病理学检查:结果显示:DOX会导致大鼠运动能力受损,焦虑行为增加,神经病理变化明显,MDA含量和TNF-α浓度显著升高,磷脂酶(PLD)和乙酰胆碱酯酶(AChE)蛋白浓度降低,此外,JNK、NF-κB和p38基因上调,Erk1基因下调:结论:外泌体疗法通过调节参与 DOX 神经毒性信号通路的标记物,改善了 DOX 的实质性神经毒性,从而改善了病理损伤和动物行为。
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来源期刊
Toxicology Research
Toxicology Research TOXICOLOGY-
CiteScore
3.60
自引率
0.00%
发文量
82
期刊介绍: A multi-disciplinary journal covering the best research in both fundamental and applied aspects of toxicology
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