Differential effects of the ascorbyl and tocopheryl derivative on the methamphetamine-induced toxic behavior and toxicity

Toxicology. 2007 Oct 30;240(1-2):96-110. doi: 10.1016/j.tox.2007.07.022. Epub 2007 Aug 9.

Abstract

A previous study showed that high doses of methamphetamine induce self-injurious behavior (SIB) in rodents. Furthermore, the combination of methamphetamine and morphine increased lethality in mice. We recently surmised that the rise in SIB and mortality induced by methamphetamine and/or morphine may be related to oxidative stress. The present study was designed to determine whether an antioxidant could inhibit SIB or mortality directly induced by methamphetamine and/or morphine. The SIB induced by 20mg/kg of methamphetamine was abolished by the administration of Na L-ascorbyl-2-phosphate (APS: 300 mg/kg), but not Na DL-alpha-tocopheryl phosphate (TPNa: 200mg/kg). In contrast, APS (300 mg/kg) and TPNa (200mg/kg) each significantly attenuated the lethality induced by methamphetamine and morphine. The present study showed that the signal intensity of superoxide adduct was increased by 20mg/kg of methamphetamine in the heart and lungs, and methamphetamine plus morphine tended to increase superoxide adduct in all of the tissues measured by ESR spin trap methods. Adduct signal induced in brain by methamphetamine administration increased in significance, but in mouse administrated methamphetamine plus morphine. There are differential effects of administration of methamphetamine and coadministration of methamphetamine plus morphine on adduct signal. These results suggest that APS and TPNa are effective for reducing methamphetamine-induced toxicity and/or toxicological behavior. While APS and TPNa each affected methamphetamine- and/or morphine-induced toxicology and/or toxicological behavior, indicating that both drugs have antioxidative effects, their effects differed.

MeSH terms

  • Animals
  • Antioxidants / pharmacokinetics
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / analogs & derivatives*
  • Ascorbic Acid / blood
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use
  • Central Nervous System Stimulants / toxicity*
  • Dopamine / metabolism
  • Electron Spin Resonance Spectroscopy
  • Free Radicals / metabolism
  • Iron-Binding Proteins / metabolism
  • Male
  • Methamphetamine / toxicity*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Morphine / toxicity
  • Neurotoxicity Syndromes* / etiology
  • Neurotoxicity Syndromes* / metabolism
  • Neurotoxicity Syndromes* / prevention & control
  • Self-Injurious Behavior* / chemically induced
  • Self-Injurious Behavior* / metabolism
  • Self-Injurious Behavior* / prevention & control
  • alpha-Tocopherol / analogs & derivatives*
  • alpha-Tocopherol / blood
  • alpha-Tocopherol / pharmacology
  • alpha-Tocopherol / therapeutic use

Substances

  • Antioxidants
  • Central Nervous System Stimulants
  • Free Radicals
  • Iron-Binding Proteins
  • ascorbate-2-phosphate
  • alpha-tocopherol phosphate
  • Methamphetamine
  • Morphine
  • alpha-Tocopherol
  • Ascorbic Acid
  • Dopamine