Neuroprotective Effects Of D-Penicillamine In The Neonatal Period: Case Reports

Abstract

“fetal copper is ….with Abstract D-penicillamine (D-PA) was first used as a potential benefit for neonatal hyperbilirubinemia (NHBI) caused by hemolytic diseases of the newborn infant or immaturity of UDP-glucuronyltransferase enzyme. In this time there was a remarkedly low incidence of retinopathy of prematurity (ROP) in the infants treated with D-PA. Later, our studies were replicated in other institutes in Hungary, Poland, the USA, India and Mexico. It is important to note that there was no intolerance or short- or long-term toxicity of the medication, in spite of the fact that D-PA was used 10-20 times higher doses in the newborn period, than those in adult age. To our concept, the bilirubin-induced neurologic dysfunction (BIND), ROP and Autism Spectrum Disorders (ASD) are neurodegenerative and neurodevelopmental diseases (NDs) of immature brain caused by accumulation of free metals, unconjugated bilirubin (UCB), and UCB-Cu complex (as prooxidant), respectively, in the basal ganglia (BG) and other relevant parts of the central nervous system (CNS). The main cause is the hemolysis of neonatal red blood cells producing a great amount of heavy metals (mainly iron and copper) which are inducing reactive oxygen species (ROS). These elements can be find in the bloodstream, and pass through the immature blood-brain-barrier (BBB). In addition, ROS contribute to increased BBB permeability creating a dangerous vitious circle in the neonatal brain.