Para-nonylphenol Toxicity Induces Oxidative Stress and Arrests the Cell Cycle in Mesenchymal Stem Cells of Bone Marrow

The mechanism of para-nonylphenol (PNP) reducing the proliferation and differentiation of bone marrow mesenchymal stem cells (MSCs) is not known. The present study was designed to investigate the mechanism. MSCs were extracted under sterile condition from Wistar rat and cultured in DMEM, containing 15 % FBS and penicillin/streptomycin until the 3rd passage, then cells were treated with 0, 0.5 and 2.5 µM of PNP for 5, 10, 15 and 20 days. We studied the viability, proliferation, cell cycle and morphology of the cells. In addition, the concentration of total protein, sodium, potassium and calcium and the activity of metabolic enzymes (ALT, AST and LDH) were determined. Also, induction of oxidative stress was estimated by determining the total antioxidant and MDA levels in addition to the activity of SOD and CAT. The concentrations of PNP caused a significant increase in metabolic enzymes activity and reduced the total protein dose dependently from day 5 to day 20. But only the higher PNP concentration reduced the sodium level and increased the calcium concentration during the treatment period. In addition, we observed a significant decrease in the total antioxidant level and of SOD and CAT activities whereas a significant increase in MDA was seen. Also, PNP stopped the cell cycle at “S” and “G2/M” phases. Para-NP, used in many industries, was able to reduce the viability and proliferation of the MSCs via metabolic and electrolyte imbalance and by induction of oxidative stress and cell cycle disruption.