Bilirubin-Induced Neurotoxicity and Environmental Impacts on Hyperbilirubinemia Development
Received Date: Oct 19, 2016 / Accepted Date: Oct 28, 2016 / Published Date: Nov 01, 2016
Hyperbilirubinemia (also known as jaundice), caused by the accumulation of unconjugated bilirubin, is one of the most common clinical diagnoses in both premature and term newborns. Owing to the fact that bilirubin is metabolized solely through glucuronidation by UDP-glucuronosyltransferase (UGT) 1A1, it is now known that immaturity of UGT1A1 in combination with overproduction of bilirubin during the developmental stage acts as a bottleneck to bilirubin elimination and predisposes the infant to high TBS levels. While neonatal jaundice is mostly benign, excessively high levels of serum bilirubin in a small percentage of newborns can cause acute or chronic bilirubin-induced neurologic dysfunction (BIND), potentially progressing to acute encephalopathy leading to irreversible brain damage and death. As a series of hereditary UGT1A1 mutations have been identified that are associated with UGT1A1 deficiency, new evidence has verified that developmental expression of UGT1A1 is a tightly controlled event, and both genetic polymorphisms and developmental regulation of UGT1A1 are major contributing factors determining the severity of hyperbilirubinemia and bilirubin-induced neurotoxicity. This review recapitulates the progress that has been made in recent years in understanding etiology and physiopathology of severe hyperbilirubinemia, investigating molecular mechanisms underlying bilirubin-induced encephalopathy, and searching for potential therapies for treating pathologic hyperbilirubinemia. Several animal models have been developed to make it possible to examine bilirubin-induced neurotoxicity from multiple directions. Moreover, environmental factors that may alleviate or worsen the condition of hyperbilirubinemia are discussed.
Keywords: Hyperbilirubinemia; Neurotoxicity; Total serum bilirubin; UDP-glucuronosyltransferase
Citation: Yueh MF, Chen S, Nguyen N, Tukey RH (2016) Bilirubin-Induced Neurotoxicity and Environmental Impacts on Hyperbilirubinemia Development. J Environ Anal Toxicol 6: 414. Doi: 10.4172/2161-0525.1000414
Copyright: © 2016 Yueh MF, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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