1. Normal glutathione levels in autopsied brain of chronic users of heroin and of cocaine.
- Author
-
Tong J, Fitzmaurice PS, Moszczynska A, Rathitharan G, Ang LC, Meyer JH, Mizrahi R, Boileau I, Furukawa Y, McCluskey T, Sailasuta N, and Kish SJ
- Subjects
- Adult, Antioxidants metabolism, Autopsy, Brain pathology, Cocaine adverse effects, Cocaine-Related Disorders metabolism, Cocaine-Related Disorders pathology, Female, Heroin adverse effects, Heroin Dependence metabolism, Heroin Dependence pathology, Humans, Male, Oxidative Stress drug effects, Oxidative Stress physiology, Brain drug effects, Brain metabolism, Cocaine administration & dosage, Glutathione metabolism, Heroin administration & dosage
- Abstract
Background: Animal studies suggest that exposure to either of the two widely used drugs of abuse, heroin or cocaine, causes depletion of the antioxidant, reduced glutathione, a hallmark of oxidative stress, in the brain. However, the relevance of the animal findings to the human is uncertain and clinical trials with the antioxidant GSH precursor n-acetylcysteine have produced mixed results in cocaine dependence., Methods: Our major objective was to compare glutathione levels, determined by an HPLC-coulometric procedure, in autopsied brain of chronic heroin (n = 11) and cocaine users (n = 9), who were positive for the drugs in the brain, to those of matched controls (n = 16). Six brain regions were examined, including caudate, hippocampus, thalamus and frontal, temporal and insular cortices., Results: In contrast to experimental animal findings, we found no statistically significant difference between mean levels of reduced or oxidized glutathione in the drug user vs. control groups. Moreover, no correlation was found between levels of drugs in the brain and those of glutathione., Conclusions: Acknowledging the many generic limitations of an autopsied human brain study and the preliminary nature of the findings, our data nevertheless suggest that any oxidative stress caused by heroin or cocaine in chronic users of the drugs might not be sufficient to cause substantial loss of stores of glutathione in the human brain, at least during early withdrawal. These findings, requiring replication, might also have some relevance to future clinical trials employing glutathione supplement therapy as an anti-oxidative strategy in chronic users of the two abused drugs., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF