ascorbic-acid and oltipraz

Human Mesenchymal stem cells (hMSCs) are multi-potential cells which are widely used in cell therapy. However, the frequently emerged senescence and decrease of differentiation capabilities limited the broad applications of MSC. Several strategies such as small molecules treatment have been widely studied and used to improve the stem characteristics bypassing the senescence but the exact mechanisms for them to reduce senescence have not been fully studied. In this study, hMSCs were treated by rapamycin, oltipraz, metformin, and vitamin C for the indicated time and these cells were subjected to senescence evaluation and trilineage differentiation. Furthermore, transcriptomics and lipidomics datasets of hMSCs after drug treatment were analyzed to interpret biological pathways responsible for their anti-senescence effects. Although four drugs exhibited significant activities in promoting MSC osteogenic differentiation, metformin is the optimal drug to promote trilineage differentiation. GO terms illustrated that the anti-aging effects of drugs were mainly associated with cellular senescence, mitotic and meiosis process. Biosynthesis of phosphatidylcholines (PC) and phosphatidylethanolamine (PE) were inhibited whereas production of phosphatidylinositols (PIs) and saturated fatty acids (SFA)/ mono-unsaturated fatty acids (MUFA) conversion was activated. Medium free fatty acids (FFA) was increased in hMSCs with different anti-aging phenotypes. Therefore, we established a comprehensive method in assessing drug intervention based on the results of transcriptomics and lipidomics. The method can be used to study different biological phenotypes upon drug intervention in MSC which will extend the clinical application of hMSCs.

Topics: Ascorbic Acid; Cell Differentiation; Cellular Senescence; Humans; Hypoglycemic Agents; Lipidomics; Mesenchymal Stem Cells; Metformin; Pyrazines; Reverse Transcriptase Inhibitors; Sirolimus; Thiones; Thiophenes; Transcriptome

1. The effects of treatment with the antischistosomal drug oltipraz on reduced glutathione (GSH), lipid peroxide (LP) and ascorbic acid (AA) concentrations in the liver, kidney and brain were studied in mice 24 h after drug administration. 2. The influence of pretreatment with cysteine or olive oil on the above variables in oltipraz-treated mice was also investigated. 3. Oltipraz, at single oral doses of 25 and 125 mg/kg, did not affect significantly the concentrations of GSH, LP or AA in any of the tissues studied. 4. At a dose of 625 mg/kg, the drug produced significant increases in GSH concentration in the liver (about 34%), kidney (38%) and brain (24%). 5. AA concentrations were not significantly affected by the drug treatment in any of the organs studied. 6. However lipid peroxide formation in the liver of mice treated with oltipraz (625 mg/kg) was less than that in control animals by about 45% (P less than 0.05). 7. In other organs it was not significantly affected by the treatment. 8. Oltipraz (625 mg/kg) was given orally to mice which were pretreated with cysteine (25, 50 and 100 mg/kg for 7 days intramuscularly). 9. The cysteine pretreatments did not affect significantly the increases in GSH caused by oltipraz alone, although they were effective in significantly increasing GSH concentrations in saline-treated mice. 10. The oltipraz-induced increases in the concentrations of GSH in liver and kidney was enhanced (by about 16%) by olive oil (0.2, 02 and 0.4 ml/mouse) when given 1 h before oltipraz treatment. 11. Concentrations of LP and AA were not significantly affected by olive oil pretreatment.

Topics: Animals; Ascorbic Acid; Brain Chemistry; Cysteine; Glutathione; Kidney; Lipid Peroxidation; Liver; Male; Mice; Olive Oil; Plant Oils; Pyrazines; Thiones; Thiophenes