Metal Dyshomeostasis in the Etiology Of Bilirubin-Induced Neurologic Dysfunction (D-Penicillamine as an Antiretroviral Drug in Hiv Or Ebola Infection Due to Vertical Transmission)

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) in the treatment of HIV or EBOLA infection due to vertical transmission. METHOD: We conducted a review searching the literature of bilirubin metabolism and of metal-homeostasis, furthermore of neonatal HIV and EBOLA infection. RESULTS: Over the past two decades there have been significant advances in our understanding of copper homeostasis and of neurodegenerative and neurodevelopmental diseases (NDs), and the pathological consequences of copper dysregulation. Thus, comprehension of metal homeostasis, details of transport and interactions with biomolecules, such as unconjugated bilirubin (UCB) or albumin, is essential for understanding the normal and pathological processes occurring in the neonatal period. UCB has a special affinity for the globus pallidus, the hippocampus, and the subthalamic nucleus. Furthermore, immaturity of the blood-brain barrier (BBB) also plays a role in 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 NDs including BIND, having impact on both protein structure (misfolding) and oxidative stress. INTERPRETATION: Free copper ion in itself or binding to UCB and forming metal-bilirubin complex(es) involved in neurologic dysfunction; therefore they are important factors for central nervous system (CNS) damage processes in BIND by the production of free radicals. Our present research article address the medical necessity of the use of a chelating agent (D-PA) in the treatment of neonatal hyperbilirubinemia (NHBI). Finally, the authors highlight that D-PA may have a huge impact on HIV or EBOLA infection caused by vertical transmission where NHBI is a very common symptom.

Keywords: Bilirubin-Induced Neurologic Dysfunction; Reactive Oxygen Species; Copper Dyshomeostasis; HIV or EBOLA infection; Neurodegeneration; D-Penicillamine in the Neonatal Period