D-PENICILLAMINE AS A NEONATAL NEUROPROTECTANT II: EFFECTS ON GASOTRANSMITTERS AND ENDOGENOUS NEUROMODULATORS

*Lajos Lakatos and György Balla

ABSTRACT

AIM: The aim of this review was to demonstrate a new concept in the etiology of bilirubin-induced neurologic dysfunction (BIND) and highlight the role of D-Penicillamine (D-PA). METHOD: We conducted a review searching the literature of bilirubin metabolism and of metal dyshomeostasis causing encephalopathy in the neonatal period. RESULTS: Unconjugated bilirubin has a special affinity for the globus pallidus, the hippocampus and the subthalamic nucleus (basal ganglia). Furthermore, immaturity of the blood-brain barrier also contributes to the development of kernicterus. Homeostasis of metal ions usually involves a huge set of proteins which regulate the proper metal biology. Metal ions, especially copper and iron play very important roles in the pathogenesis of neurodegenerative diseases including BIND, having impact on both protein structure (misfolding) and oxidative stress. INTERPRETATION: Our present research article address the medical necessity of the use of a chelating agent (D-PA) in the treatment of neonatal hyperbilirubinemia and in the prevention of retinopathy of prematurity.

Keywords: Bilirubin-induced neurologic dysfunction; Reactive oxygen species; Copper dyshomeostasis;; Neurodegeneration; D-Penicillamine in the neonatal period.