Role of antioxidants in the neurobiology of drug addiction: An update.

Relationships between protective enzymatic and non-enzymatic pro-antioxidant mechanisms and addictive substances use disorders (SUDs) are analyzed here, based on the results of previous research, as well as on the basis of our current own studies. This review introduces new aspects of comparative analysis of associations of pro-antixidant and neurobiological effects in patients taking psychoactive substances and complements very limited knowledge about relationships with SUDs from different regions, mainly Europe. In view of the few studies on relations between antioxidants and neurobiological processes acting in patients taking psychoactive substances, this review is important from the point of view of showing the state of knowledge, directions of diagnosis and treatment, and further research needed explanation. We found significant correlations between chemical elements, pro-antioxidative mechanisms, and lipoperoxidation in the development of disorders associated with use of addictive substances, therefore elements that show most relations (Pr, Na, Mn, Y, Sc, La, Cr, Al, Ca, Sb, Cd, Pb, As, Hg, Ni) may be significant factors shaping SUDs. The action of pro-antioxidant defense and lipid peroxidation depends on the pro-antioxidative activity of ions. We explain the strongest correlations between Mg and Sb, and lipoperoxidation in addicts, which proves their stimulating effect on lipoperoxidation and on the induction of oxidative stress. We discussed which mechanisms and neurobiological processes change susceptibility to SUDs. The innovation of this review is to show that addicted people have lower activity of dismutases and peroxidases than healthy ones, which indicates disorders of antioxidant system and depletion of enzymes after long-term tolerance of stressors. We explain higher level of catalases, reductases, ceruloplasmin, bilirubin, retinol, α-tocopherol and uric acid of addicts. In view of poorly understood factors affecting addiction, analysis of interactions allows for more effective understanding of pathogenetic mechanisms leading to formation of addiction and development the initiation of directed, more effective treatment (pharmacological, hormonal) and may be helpful in the diagnosis of psychoactive changes.

Enzymatic Antioxidant Defense and Polymorphic Changes in Male Infertility.

The intensification of oxidative stress and destabilization of the antioxidative defenses of an organism is a consequence of many environmental factors. We considered aspects conditioning male reproductive potential and the functionality of enzymatic antioxidative mechanisms, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), and their correlations with Li, Be, B, Na, Mg, Al, P, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Ag, Cd, Sn, Sb, Ba, Hg, Tl, Pb, and malondialdehyde (MDA), as well as genetic polymorphism IL-4v.C589T (rs2243250) in men with infertility (n = 76). A healthy normozoospermic control (n = 87) was also used. We assessed the impact of negative changes driven by oxidative stress on enzymatic antioxidative mechanisms as well as the role of MDA in the overall process. On this basis, we infer connections between disturbances in enzymatic antioxidative defense and reproductive potential. Based on a molecular analysis of the polymorphism of gene IL-4v.C589T (rs2243250) (chromosome 5) (PCR-RFLP), we considered the relationships among particular genotypes with the possibility of occurrence of male infertility. Concentrations of chemical elements were measured in the blood. The activity of antioxidants and MDA levels were measured in serum. In the infertile group, higher GPx activity was noted (6.56 nmoL·min-1·mL-1, control: 4.31 nmoL·min-1·mL-1; p = 0.004), while GR achieved a greater level in the control (17.74 nmoL·min-1·mL-1, infertile: 15.97 nmoL·min-1·mL-1, p = 0.043), which implies diversified efficiency of the first and second lines of defense. The polymorphism of IL-4v.C589T (rs2243250) was not directly connected with infertility because there were not any differences in the frequency of genotypes between the infertile and control group (p = 0.578). An analysis of genotypes CC and TT (polymorphism IL-4v.C589T (rs2243250)) indicated numerous correlations between antioxidants, chemical elements and MDA. Therefore, chemical economy, antioxidative defense and genetic conditions are connected and jointly shape male reproductive potential. Chemical elements influence antioxidative defense and male fertility; the most important modulators appeared to be Na, Ba, Al and B. The polymorphism of gene IL-4v.C589T (rs2243250) has a limited influence on antioxidative defense and the metabolism of chemical elements.