Parenteral aluminum induces liver injury in a newborn piglet model

Purpose

Parenteral nutrition-associated cholestasis remains a significant problem, especially for the surgical neonate. Aluminum is a toxic element known to contaminate parenteral nutrition. We hypothesize that parenterally administered aluminum causes liver injury similar to that seen in parenteral nutrition-associated cholestasis.

Methods

Twenty 3- to 6-day-old domestic pigs were divided into 5 equal groups. A control group received daily intravenous 0.9% sodium chloride. Each subject in experimental groups received intravenous aluminum chloride at 1500 μg/kg per day for 1, 2, 3, or 4 weeks. At the end of the study, blood was sampled for direct bilirubin and total bile acid levels. Liver, bile, and urine were sampled for aluminum content. Liver tissue was imaged by transmission electron microscopy for ultrastructural changes.

Results

Transmission electron microscopy revealed marked blunting of bile canaliculi microvilli in all experimental subjects but not the controls. Serum total bile acids correlated with the duration of aluminum exposure. The hepatic aluminum concentration correlated with the duration of aluminum exposure.

Conclusions

Parenterally infused aluminum resulted in liver injury as demonstrated by elevated bile acids and by blunting of the bile canaliculi microvilli. These findings are similar to those reported in early parenteral nutrition-associated liver disease.