Association of lipid peroxidation with hepatocellular injury in preterm infants.
BACKGROUND
We wished to determine whether cholestasis induced by total parenteral nutrition (TPN) in preterm newborn infants is associated with increased oxidative stress secondary to increased reactive oxygen intermediates. We hypothesized that elevated urinary thiobarbituric-acid-reacting substances (TBARS), a marker of oxidative stress, would be associated with hepatocellular injury as measured by serum alanine transaminase (ALT) and aspartate transaminase (AST) levels.


METHODS
Preterm infants (<35 weeks' gestation) admitted to the neonatal intensive care unit were enrolled (with their parents' informed consent) in either the 'cholestasis' group (if their direct bilirubin was >2 mg/dl [34.2 micromol/l] and duration of TPN was > or = 10 days [n = 27]) or in the control group. Urine samples for measurement of TBARS (proportionate to lipid peroxidation) and blood specimens for analysis of serum bilirubin, ALT, AST, and alkaline phosphatase were obtained within 24 hours of enrollment.


RESULTS
The cholestasis and control groups were comparable with respect to gestational age, birth weight, Apgar score, maximum FiO2, and duration of supplemental oxygen administration. Median serum direct bilirubin concentrations in the cholestasis and control groups were, respectively, 3.3 mg/dl (56.4 micromol/l) and 1.7 mg/dl (29.1 micromol/l) (P < 0.001). Serum ALT and AST levels were also elevated in the cholestasis group, but alkaline phosphatase levels did not differ significantly between the groups. Urinary levels of TBARS in all the infants were correlated with ALT and AST but did not differ significantly between cholestatic and control infants.


CONCLUSIONS
Our findings suggest that oxidant stress is associated with hepatocellular injury in preterm infants. This effect is not correlated with the degree of cholestasis.
Weinberger
Barry
B
University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ, USA. barryw@pol.net
Watorek
Kazimierz
K
Strauss
Richard
R
Witz
Gisela
G
Hiatt
Mark
M
Hegyi
Thomas
T
D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D001219:Aspartate Aminotransferases / Q000097:blood; D016022:Case-Control Studies; D002779:Cholestasis / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D015227:Lipid Peroxidation; D010289:Parenteral Nutrition, Total / Q000009:adverse effects; D012044:Regression Analysis; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase