Levels of 4-hydroxynonenal and malondialdehyde are increased in brain of human chronic users of methamphetamine

Animal studies suggest that the widely used psychostimulant drug methamphetamine (MA) can harm brain dopamine neu-rones, possibly by causing oxidative damage. However, evi-dence of oxidative damage in brain of human MA users is lacking. We tested the hypothesis that levels of two “gold standard ” products generated from lipid peroxidation, 4-hy-droxynonenal (one of the most reactive lipid peroxidation alde-hyde products) and malondialdehyde, would be elevated in post mortem brain of 16 dopamine-deficient chronic MA users compared with those in 21 matched control subjects. Derivat-ized aldehyde concentrations were determined by gas chroma-tography-mass spectrometry. In the MA group, we found significantly increased levels of 4-hydroxynonenal and malon-dialdehyde in the dopamine-rich caudate nucleus (by 67 an