Bilirubin is an endogenous substance, formed during the breakdown of hemoglobin. When there is too much of it in the body it becomes toxic. Bilirubin toxicity is well known in the central nervous system, where it is deposited in the basal ganglia, hippocampus and brainstem, including the pons and midbrain. Bilirubin is also a powerful antioxidant, which protects the central nervous system from oxidative stress, caused by staurosporine. The aim of our study was to determine the effect of bilirubin on apoptosis and necroptosis as two forms regulated cell death of astrocytes. We were also interested in how bilirubin affects the production of ATP, which serves as an indicator of cell's physiological state. As an experimental model we used astrocyte cultures of the cerebral cortex of newborn rats. As a result of a flow cytometer analysis bilirubin was found to have no effect on astrocyte apoptosis, whereas at high concentrations (100 nM and 250 nM) it increased the proportion of necroptotic cells. On the other hand, in the case of necroptosis, bilirubin has shown a hormestic effect, where at a low concentration (10 nM) it acted protectively and reduced astrocyte necroptosis, triggered by 1 µM staurosporine. Our experimental conditions did not show any effect of bilirubin on the amount of ATP in astrocytes. We came to the conclusion, that bilirubin in high concentrations is toxic to astrocytes, while in low concentrations it can also act protectively.
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