Abdel-Gawad Doaa R I, Khalil Fatma, Shehata Olfat, Ibrahim Marwa A, El-Samannoudy SalmaI, Mahdi Emad A, Shaban Nema S
Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Beni-Suef University, Shamla St. next to the Directorate of Roads and Bridges, Beni Suef 62511, Egypt.
Department of Animal and Poultry Management and Wealth Development, Faculty of Veterinary Medicine, Beni-Suef University, Shamla St. next to the Directorate of Roads and Bridges, Beni-Suef 62511, Egypt.
Toxicol Res (Camb). 2024 Oct 3;13(5):tfae159. doi: 10.1093/toxres/tfae159. eCollection 2024 Oct.
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.
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.
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.
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.
阿霉素（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，目前其应用受到限制。骨髓间充质干细胞（BM-MSCs）衍生的外泌体是一种有前景的再生疗法。在本研究中，我们研究了BM-MSCs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三组，如下：第1组（对照组），第2组（腹腔注射（i.p.）剂量为2.5mg/Kg的DOX的大鼠），和第3组（腹腔注射剂量为1.5ml/Kg的DOX和BM-MSCs衍生的外泌体的大鼠）。在实验过程中记录行为测试，三周后处死大鼠，收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导致大鼠运动功能受损并增加其焦虑样行为，出现明显的神经病理学变化，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下调。
外泌体疗法通过调节DOX神经毒性信号通路中涉及的标志物，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。
