Document Detail

A Developmental Approach to Drug-induced Liver Injury in Newborns and Children.
MedLine Citation:
PMID:  22876896     Owner:  NLM     Status:  Publisher    
The liver represents the major site of drug metabolism in humans. The developmental changes that occur in the liver's metabolic activity during foetal life and in the perinatal period are on the basis of the varied sensitivity of human newborns to many drugs. The decreased capacity of the fetal and newborn liver to metabolize, detoxify, and excrete drugs - total cytochrome P450 content in the fetal liver being 30% to 60% of adult values - may explain the prolonged actions of many drugs in the newborn, as well as their potential toxicity. On the other hand, the low levels of phase I (activation) enzymes, producing more polar reactive and often toxic metabolites, could explain the lower incidence of adverse effects of some drugs reported in newborns. Moreover, the greater capacity of newborns to synthesize glutathione is at the basis of their ability in inactivating many toxic metabolites. Here we review the acute and chronic liver toxicity due to the most widely used drugs in the neonate. We will discuss in detail the biochemical profile of the foetal and neonatal liver, and the toxic metabolites formed during the metabolism of the most widely used drugs in the neonate. The histological picture of liver disease related to the therapeutic use of drugs will be discussed, with particular emphasis on the mode of cell death involved in hepatitis induced by different drugs most frequently utilized in the neonatal intensive care units.
Faa Gavino; Ekstrom Jorgen; Castagnola Massimo; Gibo Yukio; Ottonello Giovanni; Fanos Vassilios
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-09
Journal Detail:
Title:  Current medicinal chemistry     Volume:  -     ISSN:  1875-533X     ISO Abbreviation:  Curr. Med. Chem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9440157     Medline TA:  Curr Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Istituto di Anatomia Patologica, Ospedale San Giovanni di Dio, Via Ospedale n. 60, 09124 C A G L I A R I, Sardinia, Italy.
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