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

Shinobu Ito1, Tomohisa Mori, Hideko Kanazawa

  • 1Department of Legal Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

Toxicology
|September 19, 2007
PubMed

Insights

Antioxidants like Na L-ascorbyl-2-phosphate (APS) and Na DL-alpha-tocopheryl phosphate (TPNa) reduce methamphetamine toxicity. APS inhibited self-injurious behavior, while both APS and TPNa attenuated drug-induced lethality and oxidative stress.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Toxicology

Background:

  • Methamphetamine and morphine co-administration increases lethality in mice.
  • Methamphetamine induces self-injurious behavior (SIB) in rodents.
  • Oxidative stress is hypothesized to mediate methamphetamine and/or morphine-induced SIB and mortality.

Purpose of the Study:

  • To investigate the potential of antioxidants to inhibit methamphetamine and/or morphine-induced SIB and mortality.
  • To determine if antioxidants can mitigate the oxidative stress associated with methamphetamine and/or morphine administration.

Main Methods:

  • Rodents were administered methamphetamine (20mg/kg) and/or morphine.
  • Antioxidants Na L-ascorbyl-2-phosphate (APS; 300 mg/kg) and Na DL-alpha-tocopheryl phosphate (TPNa; 200mg/kg) were administered.
  • Self-injurious behavior (SIB) and mortality were assessed.
  • Electron spin resonance (ESR) spin trap methods were used to measure superoxide adducts in various tissues.

Main Results:

  • APS (300 mg/kg) abolished methamphetamine-induced SIB, while TPNa (200mg/kg) did not.
  • Both APS (300 mg/kg) and TPNa (200mg/kg) significantly attenuated methamphetamine and morphine-induced lethality.
  • Methamphetamine administration increased superoxide adducts in heart and lungs.
  • Methamphetamine plus morphine tended to increase superoxide adducts across measured tissues.
  • Differential effects on adduct signals were observed between methamphetamine administration and co-administration with morphine.

Conclusions:

  • APS and TPNa demonstrate effectiveness in reducing methamphetamine-induced toxicity and toxicological behaviors.
  • Both APS and TPNa exhibit antioxidative effects against methamphetamine and/or morphine-induced toxicology.
  • The antioxidative effects of APS and TPNa differ, suggesting distinct mechanisms or potencies.

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