Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis: New evidence on the potential therapeutic mechanism

Hepatology, 05/16/2012

Therapy with Pentoxifylline (PTX) compared to placebo was associated with a significant reduction of oxidized fatty acids. This novel evidence supports that the beneficial effects of PTX in patients with nonalcoholic steatohepatitis (NASH) are likely partly mediated through decreasing lipid oxidation, largely free–radical mediated lipid oxidation. Additionally, this is the first report on the link between decreased oxidized lipid products and improved histological disease in the setting of a therapeutic trial in NASH.

Methods

  • Levels of multiple structurally specific oxidized fatty acids including hydroxy-octadecadenoic acids (HODEs), oxi-octadecadenoic acids (oxoODEs), and hydroxy-eicosatetraenoic acids (HETEs) were quantified by mass spectrometry in plasma obtained at baseline and at study completion in patients who completed 1 year of therapy with PTX or placebo in a randomized controlled trial.

Results

  • Therapy with PTX resulted in significant decreases on 9-HODE and 13-oxoODE, oxidized lipid products of linoleic acid (LA) linked to histological severity in NAFLD.
  • Similarly, PTX therapy was associated with significant decreases in 8-HETE, 9-HETE, and 11-HETE compared to placebo.
  • Statistically significant correlations were demonstrated between the decrease in HODEs and oxoODEs and improved histological scores of fibrosis; and between the decrease in HETEs and improved lobular inflammation.

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