Red wine but not ethanol at low doses can protect against the toxicity of methamphetamine

BR A I N R ES E A RC H 1 3 4 6 ( 2 01 0 ) 2 4 7 – 2 50 available at www.sciencedirect.com www.elsevier.com/locate/brainres Research Report Red wine but not ethanol at low doses can protect against the toxicity of methamphetamine Syed F. Ali a , S.C. Bondy b, ⁎ a Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079-9502, USA Environmental Toxicology Program, Division of Occupational Medicine, Department of Medicine, University of California, Irvine, Irvine, CA 92697-1825, USA b A R T I C LE I N FO AB S T R A C T Article history: The goal of this study was twofold: (a) to search for possible interactive effects between two Accepted 20 May 2010 common drugs of abuse, ethanol and methamphetamine. b) To inquire whether any effects Available online 27 May 2010 of ethanol could be replicated using an equivalent amount of ethanol in the form of red wine. Adult male C57/6 N mice received 2% ethanol for 8 weeks in drinking water or red wine Keywords: diluted to yield the same ethanol content. On the 9th week animals received multiple Methamphetamine injections of methamphetamine (4 × 10 mg/kg, ip, every 2 h). They were then sacrificed 72 h Parkinson's disease after treatment. Methamphetamine produced a significant depletion of dopamine and Dopamineric systems DOPAC in the striatum. Treatment with both ethanol and methamphetamine led to a Red wine reduction of striatal dopamine and DOPAC that were both non-significantly greater than Striatum that observed with methamphetamine alone. Alcohol alone produced no changes in the Neurotoxicity striatal content of dopamine or its metabolite, DOPAC. These data suggest that low doses of alcohol potentiate methamphetamine-induced neurotoxicity in mice and that this combination may be especially detrimental to the brain. However, an equivalent dose of ethanol in the form of red wine actually partially protected against methamphetamine- induced depletion of dopamine and DOPAC in red wine treated mice. This implies the presence of other agents in red wine, which may mitigate the toxicity of methamphetamine. © 2010 Elsevier B.V. All rights reserved. Introduction Alcohol has been in common use for several millennia and has been widely misused. The relationship between alcohol consumption with various diseases has been explored for decades. In early seventies several French scientists published a series of epidemiological studies showing the beneficial effects of wine consumption and the lowering of heart disease what they described as “French Paradox” (Das et al., 1999). Most, biochemical studies in the literature concerning alcohol have used moderate to high doses to better understand its mechanism of action. There are some reports suggesting that at a low concentration, alcohol may be beneficial by detoxi- fication of oxidant free radicals (Constant, 1997). However, at high concentrations it can act as a pro-oxidant by various means including induction of the mixed function oxidase CYP2E1 (Wu and Cederbaum, 2005), and formation of perox- ynitrite (Yang et al., 2008). In the scientific literature studies generally explore the effect of a single drug on a given system. However, in the real ⁎ Corresponding author. Fax: +1 949 824 2077. E-mail address: SCBONDY@UCI.EDU (S.C. Bondy). 0006-8993/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2010.05.058