Abstract
Purpose For patients with intestinal failure, parenteral nutrition (PN) is a life-saving
therapy. Unfortunately, hepatic dysfunction will occur in 40 to 60% of children on
long-term PN. While the hepatic dysfunction is likely multifactorial, one important
chemical component of the disease may be aluminum contamination of the PN. Previous
studies have shown a reduction in liver injury by decreasing the aluminum concentration
in PN in a pig model. We sought to develop a rat model of PN-associated liver disease
(PNALD) with parenteral aluminum.
Methods Adult Sprague–Dawley rats had intravenous long-term catheters placed. The control
group underwent daily injections of saline. The study rats had daily injections of
either 2 or 3 mg/kg aluminum chloride (AlCl3). At the end of 4 weeks, the rats were euthanized and liver and blood samples were
taken. The livers were analyzed and graded by a pathologist for histological evidence
of liver degeneration and acute and chronic inflammation. The serum was analyzed for
total bilirubin, alkaline phosphatase, alanine aminotransferase (ALT), and aspartate
aminotransferase (AST).
Results There was no difference in serum values of total bilirubin, alkaline phosphatase,
ALT, or AST. There was no difference in acute inflammation among the groups (1 [control],
1.2 [2 mg/kg], 1.1 [3 mg/kg]). The rats treated with parenteral aluminum had significantly
more Kupffer cells than the control group (0.1 [control], 3 [2 mg/kg], 2.2 [3 mg/kg],
p < 0.0001 [control vs. 2 mg/kg] and 0.0032 [control vs. 3 mg/kg]). There was also
more liver degeneration in the parenteral aluminum groups than the control group (1
[control], 2 [2 mg/kg], 2.5 [3 mg/kg], p = 0.0341 [control vs. 2 mg/kg] and 0.009 [control vs. 3 mg/kg]). However, there was
no difference between 2 and 3 mg/kg AlCl3 for either variable.
Conclusion This study suggests that 4 weeks of parenteral aluminum can induce chronic inflammation
and degeneration of the liver in rats. Therefore, we believe that daily injections
of parenteral aluminum can produce a viable model of PNALD in rats. However, further
studies are warranted, including measurement of serum aluminum levels in infants on
PN.
Keywords
parenteral nutrition - cholestatic liver disease - rat
