Abstract
Cholestasis as defined by a high direct bilirubin has been identified as an initial common symptom in newborn infants receiving a natural vitamin E product with high polysorbate concentrations. These studies were performed to examine the effects of Polysorbate 20 and Polysorbate 80 in combination with vitamin E on cellular toxicity, bile acid uptake and secretion in freshly isolated hepatocytes from newborn rabbits. Cellular bile acid uptake and secretion were quantitated using radiolabelled deoxycholic acid and glycocholic acid respectively. Both control and treated hepatocytes were incubated for one hour in the presence of polysorbate prior to kinetic analysis of bile acid transport. A summary of transport data is presented in the table. Transmission electron microscopy following 1 hr incubation with 0.33% Polysorbate 80 revealed cellular blebs containing intracellular milieu, loss of microvilli and loss of ribosomes from the endoplasmic reticulum. It is concluded that polysorbates selectively inhibit hepatic bile acid secretion at concentrations below that producing either cellular damage or inhibition of bile acid uptake. The observed effects were dependant on both age and the individual polysorbate.
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