NEUROPROTECTIVE EFFECTS OF D - PENICILLAMINE IN THE NEONATAL PERIOD

Abstract

Originally D-penicillamine (D-PA) was used due to its potential benefits in the treatment of neonatal hyperbilirubinemia
caused by hemolytic diseases in newborn infants or immaturity of the liver enzyme uridine 5'-diphosphoglucuronosyltransferase (UDP-glucuronosyltransferase). In that period, the prevalence of retinopathy of prematurity (ROP) in
infants who received treatment with D-PA. Later, studies were performed by different institutes in Poland, Hungary, the USA,
Mexico, and India. Short or long-term use of the medication didn’t seem to have caused toxicity or intolerance, even D-PA in
the newborn period was given in higher doses compared with the doses used in adult patients. Several bilirubin-induced
neurologic dysfunctions in the infants, including ROP and autism spectrum disorder, are possibly caused by metal
accumulation, unconjugated bilirubin (UCB), as well as UCB-copper complexes in sensitive regions of the central nervous
system. Apparently, neonatal hemolysis of red blood cells leads to an unphysiological release of copper and iron from the
cells, which pass the blood-brain-barrier (BBB) via the bloodstream. Also, reactive oxygen species contributing to an
increased BBB permeability, which creates a dangerous vicious circle in the neonatal brain. In this paper, we present two
cases of neonatal hyperbilirubinemia, which indicate the potential neuroprotective effects of D-PA.