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Phytol-induced hepatotoxicity in mice.

John T Mackie1, Barbara P Atshaves, H Ross Payne

  • 1Department of Pathobiology, Texas A&M University, TVMC, College Station, Texas, USA. john-mackie@idexx.com

Toxicologic Pathology
|February 4, 2009
PubMed
Summary

Dietary phytol causes liver injury in mice by increasing phytanic acid levels. Female mice are more susceptible to this phytol-induced hepatotoxicity due to lower sterol carrier protein-x (SCP-x) expression.

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Area of Science:

  • Biochemistry
  • Toxicology
  • Molecular Biology

Background:

  • Phytanic acid, a branched-chain saturated fatty acid, is found in dairy and ruminant fats.
  • Dietary phytol is converted to phytanic acid post-absorption.
  • Phytanic acid activates peroxisome proliferator-activated receptor alpha (PPARα), influencing fatty acid oxidation genes.

Purpose of the Study:

  • To investigate the effects of dietary phytol administration on mouse liver.
  • To determine the mechanism of phytol-induced hepatotoxicity.
  • To explore sex-based differences in susceptibility to phytol toxicity.

Main Methods:

  • Administration of dietary phytol (0.5% or 1%) to normal mice for 12-18 days.
  • Assessment of PPARα-mediated responses, including body and liver weights, peroxisome proliferation, catalase expression, and hepatocellular changes.

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  • Analysis of liver phytanic acid and pristanic acid levels, and sterol carrier protein-x (SCP-x) expression.

    • Main Results:

    • Phytol administration induced PPARα-mediated responses: lower body weight, higher liver weight, peroxisome proliferation, and hepatocellular hypertrophy/hyperplasia.
    • Hepatocellular necrosis and fatty vacuolation were observed in female mice fed 0.5% phytol and in both sexes fed 1% phytol.
    • Female mice exhibited significantly lower hepatic sterol carrier protein-x (SCP-x) expression compared to males.

    Conclusions:

    • Dietary phytol can induce selective midzonal hepatocellular necrosis in mice, a rare form of liver injury.
    • Female mice show greater susceptibility to phytol-induced hepatotoxicity.
    • Lower SCP-x expression in female mice may impair phytanic acid oxidation, contributing to their increased susceptibility.