Junchao Tong1, Paul S Fitzmaurice2, Anna Moszczynska3, Gausiha Rathitharan4, Lee-Cyn Ang5, Jeffrey H Meyer6, Romina Mizrahi7, Isabelle Boileau8, Yoshiaki Furukawa9, Tina McCluskey10, Napapon Sailasuta11, Stephen J Kish10. 1. Preclinical Imaging Unit, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Human Brain Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Addiction Imaging Research Group, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. Electronic address: Junchao.tong@camh.ca. 2. Gribbles Pathology, HealthScope, New Zealand. 3. Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA. 4. Human Brain Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Addiction Imaging Research Group, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. 5. Division of Neuropathology, London Health Sciences Centre, University of Western Ontario, London, ON, Canada. 6. Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. 7. Research Imaging Centre, Centre for Addiction and Mental Health, Institute of Medical Science, Department of Psychiatry, University of Toronto, Toronto, ON, Canada. 8. Addiction Imaging Research Group, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. 9. Department of Neurology, Juntendo Tokyo Koto Geriatric Medical Center, Faculty of Medicine, University and Post Graduate University of Juntendo, Tokyo, Japan. 10. Human Brain Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada. 11. Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
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.
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.
Authors: Ahmed O Abdel-Zaher; Mostafa G Mostafa; Hanan S M Farghaly; Mostafa M Hamdy; Randa H Abdel-Hady Journal: Behav Brain Res Date: 2013-03-05 Impact factor: 3.332
Authors: John W Haycock; Laurence Becker; Lee Ang; Yoshiaki Furukawa; Oleh Hornykiewicz; Stephen J Kish Journal: J Neurochem Date: 2003-11 Impact factor: 5.372