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Nitric oxide production and monoamine oxidase activity in cancer patients during interferon-alpha therapy

Durk Fekkes1, Arthur R Van Gool, Marjolein Bannink

  • 1Department of Neuroscience, Erasmus MC, Rotterdam, The Netherlands. d.fekkes@erasmusmc.nl

Amino Acids
|October 28, 2008
PubMed

Insights

Interferon-alpha (IFN-alpha) treatment alters nitric oxide (NO) and monoamine oxidase (MAO) levels in cancer patients. Peripheral NO production and MAO activity appear unrelated and unlikely to cause psychiatric side effects.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Oncology

Background:

  • Interferon-alpha (IFN-alpha) treatment in cancer patients has conflicting reports on nitric oxide (NO) synthesis.
  • Animal studies suggest IFN-alpha influences biogenic amines, monoamine oxidases (MAOs), and subsequently NO production via hydrogen peroxide (H2O2).

Purpose of the Study:

  • To investigate the relationship between plasma NO production and platelet MAO-B activity in cancer patients receiving IFN-alpha.
  • To assess biochemical changes during IFN-alpha therapy and their potential link to psychopathology.

Main Methods:

  • Quantified NO synthesis by measuring citrulline/arginine ratio (CIT/ARG-ratio) and total nitrite/nitrate (NOx) levels.
  • Assessed MAO-B activity in platelets of 43 cancer patients over an 8-week IFN-alpha treatment period.

Main Results:

  • MAO activity and NOx levels increased significantly compared to baseline.
  • The CIT/ARG-ratio decreased during IFN-alpha treatment.
  • No significant associations were found between NOx, MAO activity, and the CIT/ARG-ratio.
  • Few links between biochemical changes and psychopathology were observed, with changes in citrulline (CIT) and lassitude being the most consistent.

Conclusions:

  • Peripheral NO production and MAO activity are not directly related in patients treated with IFN-alpha.
  • Observed peripheral biochemical changes are unlikely to be the primary cause of significant psychiatric disturbances during IFN-alpha therapy.

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