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Naunyn Schmiedebergs Arch Pharmacol ; 396(6): 1077-1093, 2023 06.
Article in English | MEDLINE | ID: mdl-36640200

ABSTRACT

Cisplatin is widely used as an anti-neoplastic agent but is limited by its nephrotoxicity. The use of mesenchymal stem cells (MSCs) for the management of acute kidney injury (AKI) represents a new era in treatment but effective homing of administered cells is needed. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on cisplatin-induced AKI in rats after directed migration by electric field (EF). Forty-eight adult male albino rats were equally classified into four groups: control, cisplatin-treated, cisplatin plus BM-MSCs, and cisplatin plus BM-MSCs exposed to EF. Serum levels of IL-10 and TNF-α were measured by ELISA. Quantitative real-time PCR analysis for gene expression of Bcl2, Bax, caspase-3, and caspase-8 was measured. Hematoxylin and eosin (H&E) staining, periodic acid Schiff staining, and immunohistochemical analysis were also done. MSC-treated groups showed improvement of kidney function; increased serum levels of IL-10 and decreased levels of TNF-α; and increased mRNA expression of Bcl2 and decreased expression of Bax, caspase-3, and caspase-8 proteins comparable to the cisplatin-injured group. EF application increased MSCs homing with significant decrease in serum urea level and caspase-3 gene expression together with significant increase in Bcl2 expression than occurred in the MSCs group. Restoration of normal kidney histomorphology with significant decrease in immunohistochemical expression of caspase-3 protein was observed in the BM-MSCs plus EF group compared to the BM-MSCs group. EF stimulation enhanced the MSCs homing and improved their therapeutic potential on acute cisplatin nephrotoxicity.


Subject(s)
Acute Kidney Injury , Mesenchymal Stem Cells , Humans , Male , Acute Kidney Injury/chemically induced , Acute Kidney Injury/therapy , bcl-2-Associated X Protein/metabolism , Caspase 3/metabolism , Caspase 8/metabolism , Caspase 8/pharmacology , Cisplatin/toxicity , Interleukin-10/genetics , Interleukin-10/metabolism , Mesenchymal Stem Cells/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Animals , Rats
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