Effect of some phytoconstituents on Fe²⁺/ascorbate induced lipid peroxidation

851-855Transition metals like iron and copper, present inside the body system play a key role in the production of reactive oxygen radicals. These free radicals, causative agents of lipid peroxidation, not only damage proteins and DNA but also gradually changes the cellular membrane structure and ultimately leads to the loss of function and integrity. Uncontrolled lipid peroxidation results in various age related diseases, malignancy, infective diseases and injuries. Antioxidants and other phytochemical constituents present in the various plants are known to protect cells from such reactive oxygen species (ROS)-mediated damages. Here, we evaluated the effect of certain phytoconstituents present in the well-known medicinal plants on ROS scavenging using rat liver homogenate. The basal lipid peroxidation was found to be 0.1625±0.0095 ngMDA/min/mg protein, which got induced to 0.7938±0.0478 ngMDA/min/mg protein in the presence of Fe2+/ascorbate system. In this context, acteoside, berberine, catechin, 3´5-dihydroxyflavone7-o-ß-D-galacturonide-4-o-ß-D-glucopyranoside (a flavonoid glycoside from cumin), silibin and tetrahydrocurcumin decreased both basal and Fe2+/ascorbate induced lipid peroxidation as determined by thiobarbituric acid reaction. On the other hand, agnuside, andrographolide, picroside-I, negunoside, oleanolic acid, and glycerrihizin, showed enhancement in both basal and induced lipid peroxidation. Phytoconstituents which have decreased both basal and Fe2+/ascorbate induced lipid peroxidation may act as defensive against the deadly effects of ROS, causative agents of lipid peroxidation and other diseases either alone or in combination with diet/nutritional supplements

Allo-Reactivity of Mesenchymal Stem Cells in Rhesus Macaques Is Dose and Haplotype Dependent and Limits Durable Cell Engraftment In Vivo

The emerging paradigm that MSCs are immune privileged has fostered the use of “off-the-shelf” allogeneic MSC-based therapies in human clinical trials. However, this approach ignores studies in experimental animals wherein transplantation of MSCs across MHC boundaries elicits measurable allo-immune responses. To determine if MSCs are hypo-immunogeneic, we characterized the immune response in rhesus macaques following intracranial administration of allogeneic vs. autologous MSCs. This analysis revealed unambiguous evidence of productive allo-recognition based on expansion of NK, B and T cell subsets in peripheral blood and detection of allo-specific antibodies in animals administered allogeneic but not autologous MSCs. Moreover, the degree of MHC class I and II mismatch between the MSC donor and recipient significantly influenced the magnitude and nature of the allo-immune response. Consistent with these findings, real-time PCR analysis of brain tissue from female recipients administered varying doses of male, allogeneic MSCs revealed a significant inverse correlation between MSC engraftment levels and cell dose. Changes in post-transplant neutrophil and lymphocyte counts also correlated with dose and were predictive of overall MSC engraftment levels. However, secondary antigen challenge failed to elicit a measurable immune response in allogeneic recipients. Finally, extensive behavior testing of animals revealed no main effect of cell dose on motor skills, social development, or temperament. Collectively, these data indicate that allogeneic MSCs are weakly immunogenic when transplanted across MHC boundaries in rhesus macaques and this negatively impacts durable engraftment levels. Therefore the use of unrelated donor MSCs should be carefully evaluated in human patients