Lack of increased oxidative stress in catechol-O-methyltransferase (COMT)-deficient mice

Naunyn-Schmiedeberg's Archives of Pharmacology
Markus M ForsbergPekka T Männistö

Abstract

The effect of catechol-O-methyltransferase (COMT) deficiency on methamphetamine-induced hydroxyl radical production in the brain was assessed by the salicylate trapping method. Methamphetamine-induced hyperthermia was also studied. Furthermore, the effect of COMT deficiency on the activities of glutathione S-transferase, quinone reductase and liver mono-oxygenases was assessed with and without l-dopa challenge. Finally, two alternative pathways of l-dopa metabolism were evaluated. Methamphetamine increased 2,3-dihydroxybenzoic acid levels only slightly (n.s.) at the lowest dose level (2.5 mg/kg x 4 i.p.). This was accompanied by a simultaneous increase in salicylate levels so that the 2,3-dihydroxybenzoic acid/salicylate ratio decreased correspondingly. Most importantly, no COMT genotype-dependent changes were observed. However, hyperthermia was induced even at the lowest methamphetamine dose, the COMT-deficient mice being most sensitive. COMT deficiency did not significantly change the activities of liver glutathione S-transferase, quinone reductase or 7-ethoxyresorufin and 7-pentoxyresorufin O-dealkylation. In COMT-deficient female mice, l-dopa (30-80 mg/kg b.i.d. for 2 days) did not induce any significant changes in liver or...Continue Reading

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Citations

May 2, 2009·Journal of the American Society of Nephrology : JASN·Anja Haase-FielitzDuska Dragun
May 12, 2009·Biochemical Pharmacology·Jofre Tenorio-LarangaJ Arturo García-Horsman
May 3, 2012·Photodermatology, Photoimmunology & Photomedicine·Sofia MaginaDaniel Moura
Jul 16, 2010·Journal of Neurochemistry·Mikko KäenmäkiPekka T Männistö

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