Total antioxidant capacity is significantly lower in cocaine-dependent and methamphetamine-dependent patients relative to normal controls: results from a preliminary study

Abstract

Background: Oxidative stress can result in damage to the brain and other organs. To protect from oxidative damage, the human body possesses molecular defense systems, based on the activity of antioxidants, and enzymatic defense systems, including the enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Although pre-clinical research has shown that stimulant use is associated with oxidative damage, oxidative stress and the antioxidant defense systems have not been evaluated in clinical samples of stimulant-dependent patients.

Objectives: This study aimed to investigate the link between stimulant dependence and oxidative stress.

Methods: Peripheral blood samples from 174 methamphetamine (n = 48) and/or cocaine-dependent (n = 126) participants as well as 30 normal control participants were analyzed for the enzyme activities of CAT, SOD, and GSH-Px in the erythrocytes and the total antioxidant capacity and the malondialdehyde concentration in the plasma.

Results: We could show an association of stimulant dependence with a depletion of total antioxidant capacity to 54.6 ± 4.7%, which correlates with a reduced activity of the SOD to 71.3 ± 0.03% compared with healthy control participants (100%).

Conclusion: Stimulant-dependent patients had significantly lower antioxidant capacity relative to controls, suggesting that they may be at greater risk for oxidative damage to the brain and other organs.

Figures

Figure 1

Overview of the oxidative defense mechanism in human blood and tissues, AOX – antioxidant, GSH-Px – glutathione peroxidase, CAT – catalase, SOD – superoxide dismutase, ROS – reactive oxygen species

Figure 2

Mechanism of increased ROS formation in the synaptic cleft due to cocaine blockage of the dopamine transporter (DAT) in the central nervous system. A. Dopamine (DA) is released from the presynaptic cell into the synaptic cleft. B. Cocaine blocks the reuptake of dopamine into the presynaptic cell, increasing the amount of dopamine in the synaptic cleft. C. Dopamine is degraded in the synaptic cleft by two enzymes, catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO). During the reaction of the MAO, hydrogen peroxide is formed, from which oxygen radicals can form. DOPAC – dihydroxyphenyl acetic acid, 3MT – 3-methoxytyramine, HVA – homovanillic acid

Figure 3

Spearman correlation of the superoxide dismutase activity (SOD) and the total antioxidant capacity (TAC) of control (empty circles) and patients (full circles) with 95 % confidence intervals (grey lines).

Figure 4

Histogramms for the frequencies of (A) total antioxidant capacity (TAC) and (B) superoxide dismutase (SOD) activity, separated by the stimulant source compared to the control