Aluminum Exposure from Parenteral Nutrition: Early Bile Canaliculus Changes of the Hepatocyte
Amanda R Hall1, Ha Le2, Chris Arnold3
1Department of Surgery, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada. arb743@mail.usask.ca.
Insights
Aluminum in parenteral nutrition (PN) may harm liver cells in neonates. This study found that higher aluminum levels in PN caused structural changes in piglet hepatocytes, potentially impairing bile flow.
Area of Science:
- Hepatology
- Neonatal Medicine
- Toxicology
Background:
- Parenteral nutrition-associated liver disease (PNALD) affects neonates requiring long-term parenteral nutrition (PN).
- Aluminum (Al) contamination in infant PN is a concern.
- Aluminum's role in PNALD pathogenesis is hypothesized but not fully understood.
Purpose of the Study:
- To investigate the impact of aluminum exposure on hepatocytes in a neonatal piglet model.
- To determine if aluminum in PN contributes to parenteral nutrition-associated liver disease.
Main Methods:
- A randomized control trial was conducted using Yucatan piglets (3-6 days old) receiving PN.
- Two groups were established: high Al (63 µg/kg/day) and low Al (24 µg/kg/day).
- Serum total bile acids (TBA) were monitored, and liver tissue was analyzed using transmission electron microscopy (TEM) for bile canaliculus morphometry.
Main Results:
- Piglets receiving high Al PN exhibited smaller bile canalicular spaces compared to the low Al group.
- High Al exposure resulted in shorter microvilli in the bile canaliculi.
- Serum TBA levels did not differ significantly between the high and low Al groups.
Conclusions:
- Aluminum exposure in PN induces structural alterations in hepatocytes, specifically affecting bile canaliculi.
- Shortened microvilli in hepatocytes due to high Al may reduce the functional area for bile excretion.
- These structural changes suggest a mechanism by which aluminum could impair bile flow and contribute to PNALD.
Abstract:
Background: Neonates on long-term parenteral nutrition (PN) may develop parenteral nutrition-associated liver disease (PNALD). Aluminum (Al) is a known contaminant of infant PN, and we hypothesize that it substantially contributes to PNALD. In this study, we aim to assess the impact of Al on hepatocytes in a piglet model. Methods: We conducted a randomized control trial using a Yucatan piglet PN model. Piglets, aged 3⁻6 days, were placed into two groups. The high Al group (n = 8) received PN with 63 µg/kg/day of Al, while the low Al group (n = 7) received PN with 24 µg/kg/day of Al. Serum samples for total bile acids (TBA) were collected over two weeks, and liver tissue was obtained at the end of the experiment. Bile canaliculus morphometry were studied by transmission electron microscopy (TEM) and ImageJ software analysis. Results: The canalicular space was smaller and the microvilli were shorter in the high Al group than in the low Al group. There was no difference in the TBA between the groups. Conclusions: Al causes structural changes in the hepatocytes despite unaltered serum bile acids. High Al in PN is associated with short microvilli, which could decrease the functional excretion area of the hepatocytes and impair bile flow.
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