Oxidized Guanine Species Research Articles

Oxidative Stress Markers in Sputum

Although oxidative stress is thought to play a pivotal role in the pathogenesis of inflammatory airway diseases, its assessment in clinical practice remains elusive. In recent years, it has been conceptualized that oxidative stress markers in sputum should be employed to monitor oxidative processes in patients with asthma, chronic obstructive pulmonary disease (COPD), or cystic fibrosis (CF). In this review, the use of sputum-based oxidative markers was explored and potential clinical applications were considered. Among lipid peroxidation-derived products, 8-isoprostane and malondialdehyde have been the most frequently investigated, while nitrosothiols and nitrotyrosine may serve as markers of nitrosative stress. Several studies have showed higher levels of these products in patients with asthma, COPD, or CF compared to healthy subjects. Marker concentrations could be further increased during exacerbations and decreased along with recovery of these diseases. Measurement of oxidized guanine species and antioxidant enzymes in the sputum could be other approaches for assessing oxidative stress in pulmonary patients. Collectively, even though there are promising findings in this field, further clinical studies using more established detection techniques are needed to clearly show the benefit of these measurements in the follow-up of patients with inflammatory airway diseases.

Oxidative stress in bipolar and schizophrenia patients

Oxidative stress has an important place in studies investigating the pathophysiology of psychiatric diseases. In spite of this fact, longitudinal studies are required to clarify the subject. Therefore, in this study, we examined lipid peroxidation, protein oxidation, total oxidized guanine species, superoxide dismutase (SOD) and total glutathione (GSH) levels in blood collected from adult bipolar patients (n=18) during manic and euthymic episodes, schizophrenic patients (n=18) during acute psychotic attack and remission phases and the control group (n=18). There was a significant increase in the level of lipid peroxidation in the bipolar disorder manic episode group (BD-ME) compared to control group. The level of protein oxidation was significantly higher in the schizophrenia acute psychotic attack group (SZ-APA) compared to the control group. The level of total oxidized guanine species was statistically higher in all psychiatric groups compared to the control group. There was no significant difference among the groups with regard to SOD and GSH. Consequently, we believe that lipid peroxidation may be effective in the pathogenesis of bipolar patients; that protein oxidation may be of importance in the pathogenesis of schizophrenia and that total oxidized guanine species may be crucial in the pathogeneses of both psychiatric disorders.

Oxidative damage to nucleic acids and benzo(a)pyrene-7,8-diol-9,10-epoxide-DNA adducts and chromosomal aberration in children with psoriasis repeatedly exposed to crude coal tar ointment and UV radiation.

The paper presents a prospective cohort study. Observed group was formed of children with plaque psoriasis (n=19) treated by Goeckerman therapy (GT). The study describes adverse (side) effects associated with application of GT (combined exposure of 3% crude coal tar ointment and UV radiation). After GT we found significantly increased markers of oxidative stress (8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), significantly increased levels of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) DNA adducts (BPDE-DNA), and significantly increased levels of total number of chromosomal aberrations in peripheral lymphocytes. We found significant relationship between (1) time of UV exposure and total number of aberrated cells and (2) daily topical application of 3% crude coal tar ointment (% of body surface) and level of BPDE-DNA adducts. The findings indicated increased hazard of oxidative stress and genotoxic effects related to the treatment. However, it must be noted that the oxidized guanine species and BPDE-DNA adducts also reflect individual variations in metabolic enzyme activity (different extent of bioactivation of benzo[a]pyrene to BPDE) and overall efficiency of DNA/RNA repair system. The study confirmed good effectiveness of the GT (significantly decreased PASI score).

Mechanism of DNA damage by thiocyanate radicals

Purpose : It was previously shown that γ-irradiation of aqueous solutions of plasmid DNA in the presence of millimolar concentrations of thiocyanate ions leads to the formation in very high yields of sites recognized by the base excision repair endonuclease formamido-pyrimidine-DNA N -glycosylase (FPG). The authors wished to characterize the mechanism responsible for the production of these FPG-sensitive sites. Materials and methods : An aqueous solution of plasmid DNA containing thiocyanate ions was irradiated with 137 Cs γ-rays. After irradiation, aliquots were treated with FPG. Break yields were determined using neutral agarose gel electrophoresis. Results : The yield of FPG-sensitive sites decreased with decreasing enzyme activity, increasing thiocyanate concentration, increasing dose-rate, increasing ionic strength, increasing nitrite or iodide concentration, and decreasing oxygen concentration. Conclusions: The observations suggest that the monomeric thiocyanate radical SCN •is an intermediate in the reaction, and that the yields of FPG-sensitive sites are determined by competition between the disproportionation of the dimeric radical anion (SCN) 2 •- and the fate of a one-electron oxidized guanine species in DNA. The latter can react with oxygen to produce an FPGsensitive site or can be reduced without producing an FPGsensitive site. The results help to clarify the mechanisms responsible for DNA damage by the direct eÚect of ionizing radiation.