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

被引：0

作者：

Abdel-Gawad, Doaa R., I ^{[1
]}

Khalil, Fatma ^{[2
]}

Shehata, Olfat ^{[3
]}

Ibrahim, Marwa A. ^{[4
]}

El-Samannoudy, Salmai ^{[5
]}

Mahdi, Emad A. ^{[6
]}

Shaban, Nema S. ^{[7
]}

机构：

[1] Beni Suef Univ, Dept Toxicol & Forens Med, Fac Vet Med, Shamla St Next Directorate Rd & Bridges, Bani Suwayf 62511, Egypt

[2] Beni Suef Univ, Dept Anim & Poultry Management & Wealth Dev, Shamla St Next Directorate Rd & Bridges, Bani Suwayf 62511, Egypt

[3] Beni Suef Univ, Dept Clin Pathol, Shamla St Next Directorate Rd & Bridges, Bani Suwayf 62511, Egypt

[4] Cairo Univ, Dept Biochem & Mol Biol, Block 17102 8th Dist Obour City, Giza 12211, Egypt

[5] Cairo Univ, Dept Physiol, 81 Dist 9 Neighborhood 4 Sheikh Zayed, Giza 12211, Egypt

[6] Beni Suef Univ, Dept Pathol, Bani Suwayf, Egypt

[7] Beni Suef Univ, Dept Pharmacol, POB 62511,Shamla St Next Directorate Rd & Bridges, Bani Suwayf, Egypt

来源：

TOXICOLOGY RESEARCH | 2024年 / 13卷 / 05期

关键词：

Doxorubicin; BM-MSCs derived exosomes; Neurotoxicity; Behavioral tests; RT-PCR; ELISA; EXTRACELLULAR VESICLES; IN-VITRO; EXPRESSION; CARDIOTOXICITY; IMPAIRMENT; DISEASE; STRESS; DAMAGE; HEART;

D O I：

10.1093/toxres/tfae159

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

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-alpha concentration, reduction of phospholipase (PLD) and acetylcholinesterase (AChE) protein concentration in addition, there were up regulation of JNK, NF-kappa B 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. Graphical Abstract

引用

页数：12