Xanthine Dehydrogenase Inhibition Stimulates Growth and Development of Human Brain Derived Cells

Abstract

Background: Reactive Oxygen Species (ROS) play a critical role in development of number pathologies. Xanthine Oxidase (XO) as well as the Xanthine Dehydrogenase (XDH) are two enzymes responsible for the last steps of purine catabolism, hydroxylation of a wide variety pyrimidines, and the initiation of ROS synthesis. In our current experiments we have analyzed whether exogenously added allopurinol, not only the inhibitor of XO but also XDH, is capable for in vitro human brain derived cells growth, development and proliferation. Methods: We have used described by Mark Mattson's neuronal cell culturing technique to seed and keep cells in vitro over 12 days. The death of the cells was visualized by the staining with Trypan Blue. Pixcavator and Image Tool programs served for the calculation of the cells' number and size. Results: In comparison with the control group exogenously added xanthine as well as NAD + or addition of NAD + along with xanthine didn't play any critical role. Only the group, treated with NAD + , xanthine and allopurinol promoted elevation of the cells' number in the statistically significant way on the day 12 th. Number of the death cells in comparison with the control groups in the cells groups treated with the xanthine, NAD + , as well as allopurinol was less, whereas in the NAD + and xanthine treated group this number was higher than in the control group. Conclusion: We have concluded, that treatment with the low concentration of allopurinol, will guarantee the survival of the cells, decrease the number of the death cells and promote the proliferative processes. These conclusions are similar for allopurinol treatment in condition of exogenously stimulated activity of XO/XDH as well as endogenously stimulated activity of these enzymes.

Albumin microparticles as the carriers for allopurinol and applicable for the treatment of ischemic stroke

“…In our studies, we have shown that inhibition of XO by its classical inhibitor might initiate regenerative processes in neuronal cell culture by the inhibition of purine catabolism by feedback mechanism as well as by the inhibition of XOgenerated ROS [26][27][28]. On the other hand, we also propose the utility of such albumin particles for the treatment of stroke.…”