Extracellular vesicles derived from bone marrow mesenchymal stem cells repair functional and structural rat adrenal gland damage induced by fluoride

• Published in: Life sciences (1973) Vol. 270; p. 119122
• Main Authors: Faruk, Eman Mohamed, Alasmari, Wardah Abdullah, Fouad, Hanan, Nafea, Ola Elsayed, Hasan, Rehab Abd Allah
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.04.2021; Elsevier BV
• Subjects: Adrenal glands; Adrenal Glands - metabolism; Adrenocorticotropic hormone; Animals; Antioxidants; Biomarkers; Bone marrow; Bone Marrow Cells - cytology; Bone marrow mesenchymal stem cells; Catalase; Cell Differentiation - drug effects; Corticosterone; Drinking water; Extracellular vesicles; Extracellular Vesicles - metabolism; Extracellular Vesicles - transplantation; Female; Flow cytometry; Fluoride; Fluorides; Fluorides - adverse effects; Fluorides - metabolism; Gene expression; Genes; Malondialdehyde; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchymal Stem Cells - physiology; Microscopy, Electron, Transmission - methods; Oral administration; Oxidants; Oxidizing agents; Quantitation; Rats; Sodium fluoride; Stem cell transplantation; Stem cells; Steroidogenesis; Structural damage; Structure-function relationships; Superoxide dismutase; Toxicity; Toxins; Transmission electron microscopy; Vesicles; Extracellular vesicles; Steroidogenesis; Fluoride; Adrenal glands; Bone marrow mesenchymal stem cells; Corticosterone
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.119122

The adrenal glands have striking morpho-biochemical features that render them vulnerable to the effects of toxins. Aims: This study was conducted to explore the therapeutic utility of extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) against fluoride-induced adrenal toxicity. Materials and methods: The work included isolation and further identification of BMSC-EVs by transmission electron microscopy and flow cytometric analysis. Adrenal toxicity in rats was induced by oral administration of 300 ppm of sodium fluoride (NaF) in drinking water for 60 days followed by a single dose injection of BMSC-EVs. The effects of BMSC-EVs against NaF was evaluated by adrenal oxidant/antioxidant biomarkers, hormonal assay of plasma adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) and mRNA gene expression quantitation for adrenal cortical steroidogenic pathway-encoding genes. Histopathological examination of the adrenal tissue was performed. Key findings: BMSC-EVs were effectively isolated and characterized. NaF exposure decreased adrenal superoxide dismutase and catalase activities, increased adrenal malondialdehyde levels, elevated plasma ACTH, diminished CORT concentrations and downregulated the adrenal cortical steroidogenic pathway-encoding genes. In addition, NaF-induced marked adrenal histopathological lesions. Significance: BMSC-EVs treatment repaired damaged adrenal tissue and recovered its function greatly following NaF consumption. BMSC-EVs reversed the toxic effects of NaF and reprogramed injured adrenal cells by activating regenerative processes. [Display omitted] •Fluoride negatively influenced adrenals structures.•Fluoride interfered with steroid biosynthesis.•BMSC-EVs mitigated the toxic effects of fluoride on adrenals.•BMSC-EVs reprogramed injured adrenal cells by activating regenerative processes.