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Fish oil protects mice against acetaminophen hepatotoxicity in vivo
Author(s) -
Speck Robert F.,
Lauterburg Bernhard H.
Publication year - 1991
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840130325
Subject(s) - acetaminophen , glucuronidation , chemistry , fish oil , pharmacology , glutathione , in vivo , liver injury , biochemistry , medicine , endocrinology , microsome , biology , enzyme , fish <actinopterygii> , microbiology and biotechnology , fishery
Recent observations suggest that products of nonparenchymal liver cells such as eicosanoids and cytokines might play a role in the expression of liver injury after administration of acetaminophen and other noxious agents. We therefore investigated the effect of a fish oil diet, which results in the generation of eicosanoids with altered biological properties and suppresses the production of certain cytokines on acetaminophen hepatotoxicity. Mice were fed a diet with either 20% fish oil containing n‐3 fatty acids or 20% olive oil containing n‐6 fatty acids for 2 wk. Cytochrome P‐450 activity and the concentration of glutathione were similar in the two groups before acetaminophen administration. Nevertheless, 24 hr after the administration of 375 mg/kg acetaminophen intraperitoneally, the extent of centrilobular necrosis and the activity of ALT in plasma were significantly lower in the n‐3 fatty acid group (median = 277 vs. 3,367 IU/L; p < 0.001). In the n‐3 fatty acid group covalent binding of the drug to liver proteins (0.19 ± 0.03 vs. 0.67 ± 0.07 nmol/mg protein; p < 0.01) and the median plasma concentration of acetaminophen (0.1 vs. 0.6 mmol/L) were significantly lower 3 hr after dosing. Mice fed the n‐3 fatty acid diet excreted less acetaminophen sulfate but significantly more acetaminophen glucuronide in 24 hr. Thus the major protective effect of the fish oil diet appears to be an increased clearance of acetaminophen resulting from a stimulation of the glucuronidation of acetaminophen, which may be due to the fluidization of microsomal membranes by fish oil. (H EPATOLOGY 1991;13:557–561.)