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Abstract
BACKGROUND
Paracetamol (APAP) hepatotoxicity remains the leading cause of drug-induced liver failure. Fish oil, which contains ω-3 fatty
acids, has demonstrated therapeutic efficacy in several models of liver disease. Evidence for its use in APAP intoxication,
however, is conflicting. The effects of fish oil supplementation on APAP-induced liver failure were investigated.
METHODS
Ten C57BL6/J mice were fed a diet based on menhaden fish oil (MEN) or soybean oil (SOY) for 3 weeks followed by APAP intoxication.
In a second experiment, the prefeeding period was reduced to 5 days. In a third experiment, 10 mice received the study diets
for 3 weeks, after which they received chronic, low-dose APAP administration for another 4 weeks. Finally, 10 mice received
oral parenteral nutrition supplemented with either intravenous (IV) soybean-based or fish oil-based lipid emulsion for 19
days, followed by APAP intoxication.
RESULTS
The extent of hepatocellular necrosis (3.8 ± 0.2 vs 2.8 ± 0.2; P = .021) and serum alanine aminotransferase values (2807 ±
785 vs 554 ± 141 IU/L; P = .048) were significantly elevated in mice fed a MEN diet compared with SOY-diet fed controls. Long-term,
low-dose APAP administration did not lead to liver injury irrespective of study diet. Pretreatment with soybean- or fish oil-based
IV lipid emulsions followed by APAP intoxication demonstrated no significant differences in hepatic injury between groups.
CONCLUSION
Within therapeutic ranges, APAP is harmless to the liver irrespective of dietary fat composition. IV use of fish oil did not
increase APAP-induced hepatotoxicity, but animals fed a fish oil-based diet were more susceptible, rather than resistant,
to APAP-induced hepatotoxicity.
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Authors
de Meijer VE, Kalish BT, Meisel JA, Le HD, Puder M
Institution
Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Source
JPEN. Journal of parenteral and enteral nutrition 37:2 2013 Mar pg 268-73Pub Type(s)
Journal ArticleLanguage
eng
PubMed ID
22714592