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.
Georg Thieme Verlag KG Stuttgart · New York.