Sulfasalazine and Chromotrope 2B reduce oxidative stress in murine bone marrow-derived mesenchymal stem cells

Abstract

With advancing age of stem cells, dysregulation of various processes at the cellular level occurs, thereby decreasing their regeneration potential. One of the changes that occurs during the aging process is the accumulation of reactive oxygen species (ROS), which accelerates the processes of cellular senescence and cell death. The aim of this study is to evaluate two antioxidant compounds; Chromotrope 2B and Sulfasalazine, for their antioxidant effects on young and old rat bone marrow mesenchymal stem cells (MSCs). Oxidative stress was induced in MSCs by 5 µM dexamethasone for 96h and the cells were treated with Chromotrope 2B or Sulfasalazine, 50 µM each. The effects of antioxidant treatment following oxidative stress induction was evaluated by transcriptional profiling of genes involved in the oxidative stress and telomere maintenance. Expression levels of Cat, Gpx7, Sod1, Dhcr24, Idh1, and Txnrd2 were found to be increased in young MSCs (yMSCs) as a result of oxidative stress, while Duox2, Parp1, and Tert1 expression were found to be decreased as compared to the control. In old MSCs (oMSCs), the expressions of Dhcr24, Txnrd2, and Parp1 increased, while that of Duox2, Gpx7, Idh1, and Sod1 decreased following oxidative stress. In both MSC groups, Chromotrope 2B prompted decrease in the ROS generation before and after the induction of oxidative stress. In oMSCs, ROS content was significantly reduced in the Sulfasalazine treated group. Our findings suggest that both Chromotrope 2B and Sulfasalazine possess the potential to reduce the ROS content in both age groups, though the latter was found to be more potent. These compounds can be used to precondition MSCs to enhance their regenerative potential for future cell-based therapeutics.