8-hydroxy-2--deoxyguanosine and Psoriasis

Molecular epidemiology has linked ultraviolet-induced DNA damage with mutagenesis and skin carcinogenesis. Ultraviolet radiation may damage DNA in one of two ways: either directly, leading to lesions such as cyclobutane thymine dimers (T<>T), or indirectly, via photosensitizers that generate free radical species that may ultimately produce such oxidative lesions as 8-oxo-2'-deoxyguanosine. We report the results of a pilot, case control study in which seven, healthy, human volunteers (skin type II; aged 23-56 y; three male, four female) received a suberythemal dose of whole body irradiation from ultraviolet-A-emitting fluorescent tubes used in psoralen plus ultraviolet A therapy. First void, mid-stream urine samples were collected pre-exposure and daily postexposure, for up to 13 d. Analysis of urinary 8-oxo-2'-deoxyguanosine and cyclobutane thymine dimers was by competitive enzyme-linked immunosorbent assay (interassay coefficient of variation < or = 10%) and compared with a matched, control group of unirradiated individuals. A maximal increase in levels of urinary 8-oxo-2'-deoxyguanosine was seen 4 d post-ultraviolet exposure. A subsequent reduction was noted, before finally returning to baseline. Similarly, cyclobutane thymine dimer levels peaked 3 d postexposure, before returning to baseline. In contrast to the 8-oxo-2'-deoxyguanosine analysis, however, a second peak was noted at days 9-11, before again returning to baseline. This is the first report examining urinary 8-oxo-2'-deoxyguanosine and cyclobutane thymine dimers following ultraviolet exposure of healthy human subjects. This work illustrates the induction and time course for excretion of ultraviolet-induced lesions, perhaps alluding to repair and ultimately offering the potential to define psoralen plus ultraviolet A dosage regimes in terms of minimizing DNA damage and hence cancer risk.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Case-Control Studies; Deoxyguanosine; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Pilot Projects; Psoriasis; PUVA Therapy; Pyrimidine Dimers; Reproducibility of Results; Skin Neoplasms; Ultraviolet Rays

Psoriasis is an immune-mediated chronic inflammatory skin disease that is seen in 1%–3% of the population. It is characterized by symmetrical papulosquamous lesions on the scalp, knees, elbows, sacral region, and extensor surfaces of the extremities. Psoriasis affects both sexes equally. It is thought that reactive oxygen species have an important role in inflammatory skin diseases, especially in psoriasis. There are few studies investigating serum oxidant-antioxidant levels in psoriasis. In this study, we aimed to investigate serum oxidant and antioxidant levels in psoriasis and their effects on its pathogenesis.. Included in this study were 50 patients with psoriasis who had not been treated with any systemic medication and 45 healthy volunteers (control group). The total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA), and 8-hydroxy 2’-deoxyguanosine (8H2D) were studied via venous blood sampling. The parameters were measured spectrophotometrically. The study was approved by the Local Ethics Committee of the Atatürk University Faculty of Medicine.. The mean ages of the patients and control group were 32.48 (±14.45) and 35.64 (±17.40) years, respectively. Of the patients, 23 were male and 27 were female. Of the healthy volunteers, 20 were male and 25 were female. The mean disease duration was 8.77 (±6.90) years. The mean Psoriasis Area and Severity Index (PASI) score was 11.41 (±9.62). The mean TOS levels of the patient and control groups were 63.12 (±33.23) and 4.50 (±9.74), respectively. This difference was statistically significant (P = 0.00). The mean TAS levels of the patient and control groups were 3.15 (±0.70) and 3.16 (±0.44), respectively, without any statistically significant difference. The mean MDA levels in the patient and control groups were 14.84 (±6.66) and 12.77 (±4.87), respectively, without any statistically significant difference. The mean 8H2D levels of the patient and control groups were 16,781.2 (±5918.95) and 15,276.13 (±6084.95), respectively. This difference was also not statistically significant. There was no correlation between PASI scores and the above-mentioned parameters.. In the present study, the TOS levels showed a significant statistical difference between the psoriasis and control groups. This finding supports the effect of the oxidant system in the pathogenesis of psoriasis. This was the first study to investigate MDA, TOS, TAS, and 8H2D levels together in patients with psoriasis. More studies are needed to clearly understand the relationship between psoriasis and the oxidant-antioxidant system.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Antioxidants; Female; Humans; Male; Malondialdehyde; Middle Aged; Oxidants; Psoriasis; Young Adult

Topics: 8-Hydroxy-2'-Deoxyguanosine; Deoxyguanosine; Dermatitis, Atopic; Humans; Psoriasis

The involvement of oxidative stress in the pathogenesis of various skin disorders has been suggested for decades. However, few clinical studies have assessed oxidative stress in skin diseases. The easiest and least invasive method to assess oxidative stress in patients may be the measurement of oxidation products in urine.. This study aims to assess oxidative stress in psoriasis and atopic dermatitis patients.. Urine samples were collected from 29 psoriasis patients (25 males and 4 females), 21 atopic dermatitis patients (14 males and 7 females) and 20 healthy controls (16 males and 4 females). The severity and extent of psoriasis and atopic dermatitis was assessed by their area and severity index. We measured nitrate as a metabolite of nitric oxide, malondialdehyde as a major lipid oxidation product, and 8-hydroxydeoxyguanosine (8-OHdG) as a DNA oxidation marker.. Urinary nitrate and 8-OHdG levels, but not malondialdehyde, were significantly higher in psoriasis patients than those in healthy controls. On the contrary, only urinary nitrate level was significantly higher in atopic dermatitis patients than those in healthy controls. The severity and extent of both psoriasis and atopic dermatitis significantly correlated with urinary nitrate level and malondialdehyde level, but it did not correlate with urinary 8-OHdG level.. Measurement of these three urinary oxidative products is non-invasive. Above all, measurement of urinary nitrate may be most useful in the clinical assessment of oxidative stress in both psoriasis and atopic dermatitis patients. There is a possibility that urinary 8-OHdG level may indicate the different pathogenesis between psoriasis and atopic dermatitis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Case-Control Studies; Deoxyguanosine; Dermatitis, Atopic; Female; Humans; Male; Malondialdehyde; Oxidative Stress; Psoriasis

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Deoxyguanosine; DNA Damage; Female; Humans; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Oxidative Stress; Psoriasis; PUVA Therapy; Ultraviolet Therapy

Psoralen in conjunction with UVA (PUVA) is perhaps the most effective treatment for psoriasis. It is, however, a risk factor for skin cancer in these patients and there is a need to develop non-invasive assays reflective of treatment-induced DNA damage. We report here the assessment of two important lesions, thymine dimer (T<>T) and 8-oxo-2'-deoxyguanosine (8-OHdG), in the urine of psoriasis patients. It was found that, once corrected for urine concentration, the psoriatic group had significantly higher (P<0. 0001) urinary levels of thymine dimers compared to the control group. No significant differences in urinary 8-OHdG levels were noted between the psoriatic, atopic dermatitis and control groups. Therefore biomonitoring of therapy from the very start with this simple and non-invasive assay could perhaps be an effective measure of the risk involved with the treatment allowing optimization for minimal-risk therapy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Aged; Aged, 80 and over; Deoxyguanosine; DNA Damage; Female; Humans; Male; Middle Aged; Poly T; Psoriasis; PUVA Therapy; Pyrimidine Dimers; Risk Assessment