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    Evaluation of oxidative stress via protein expression of glutathione S-transferase and cytochrome p450 (CYP450) soenzymes in psoriasis vulgaris patients treated with methotrexate
    (Taylor & Francis Ltd, 2018) Akbulak, Ozge; Karadag, Ayse Serap; Akdeniz, Necmettin; Ozkanli, Seyma; Ozlu, Emin; Zemheri, Ebru; Oguztuzun, Serpil
    Introduction: Oxidative stress is the imbalance between oxidant-antioxidant systems and may play a major role in the psoriasis pathogenesis. Cytochrome (CYP) is a family of enzymes that are responsible for the metabolism of various endogenous and exogenous substances such as drug metabolism. Most importantly, the antioxidant system is the glutathione S-transferases (GST), which decrease oxidative stress by reducing oxidative products.Aim: We aimed to evaluate the expressions of isoenzymes of GST and CYP families and the beneficial role of metotrexate (MTX) in this process.Material and methods: This study included 21 patients with psoriasis and 22 healthy subjects. We treated all the patients with 10-15mg/week of MTX for minimum 12weeks. Expressions of GST and CYP enzymes were assessed by immunohistochemical staining.Results: GSTK1, GSTM1 and GSTT1 expressions were significantly higher in the psoriasis tissues than in the control tissues (p<0.05; p<0.05; p<0.05, respectively). In the psoriasis patients, GSTO1 expression was similar the control group. CYP1B1 and CYP2E1 expressions were significantly higher in the pre-treatment and post-treatment psoriasis tissues than in the control tissues (p<0.05; p<0.05; p<0.05; p<0.05, respectively).Conclusion: We found a significant increase in the tissue levels of, either expression of GST, or CYP, which has important role in drug metabolism and oxidative stress. MTX treatment resulted in marked clinical improvement, yet we found that MTX did not have any significant effect on these parameters. CYP2E1 is especially the most important enzyme for MTX metabolism since it is the primarily responsible of the toxic metabolism of various drugs. The other experimental studies involving greater number of patients and other different drug are needed to enlighten the role of oxidant and antioxidant systems and the other possible mechanisms for the pathogenesis of psoriasis.
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    The investigation of antimicrobial peptides expression and its related interaction with methotrexate treatment in patients with psoriasis vulgaris
    (Taylor & Francis Ltd, 2017) Ozlu, Emin; Karadag, Ayse Serap; Ozkanli, Seyma; Oguztuzun, Serpil; Akbulak, Ozge; Uzuncakmak, Tugba Kevser; Akdeniz, Necmettin
    Background: Psoriasis is a chronic, inflammatory and immune-mediated disease. Recently, the role of antimicrobial peptides (AMPs) such as human beta defensins (hBDs) in the pathogenesis of psoriasis has been investigated. We aimed to evaluate the expression profiles of hBD-1 and hBD-2 in psoriatic skin before and after methotrexate (MTX) therapy and to compare healthy controls. Methods: Immunohistochemical expressions of hBD-1 and hBD-2 were assessed in 16 patients with psoriasis vulgaris and 20 normal skin biopsies from healthy controls. The patients were administered a 12 week of MTX and skin biopsy samples were obtained from the lesional skin of the patients pre-/posttreatment and normal body of the healthy controls. Results: The median (range) Psoriasis Area and Severity Index (PASI) value was 21.6 (8.2-27.7) before the treatment whereas; 3.05 (1-23.4) after the treatment. hBD-1 expression in psoriasis patients was significantly higher as compared to the healthy controls before treatment (p > 0.01). No significant difference was observed between psoriasis patients and healthy controls in terms of hBD-2 expression before treatment (p > 0.05). No significant difference was observed between before-after MTX treatment in terms of hBD-1 and hBD-2 expression levels in psoriasis patients (p > 0.05). Conclusions: These findings suggest a role for hBD-1 in psoriasis pathogenesis. But MTX treatment does not affect on hBD-1 and hBD-2 expressions. Further studies are needed to assess the roles of these AMPs in psoriasis etiopathogenesis.
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    An investigation of cytochrome p450 (CYP) and glutathione S-transferase (GST) isoenzyme protein expression and related interactions with phototherapy in patients with psoriasis vulgaris
    (Wiley-Blackwell, 2017) Karadag, Ayse S.; Uzuncakmak, Tugba K.; Ozkanli, Seyma; Oguztuzun, Serpil; Moran, Busra; Akbulak, Ozge; Akdeniz, Necmettin
    Oxidative stress may play an important role in the pathogenesis of psoriasis. Glutathione S-transferases (GSTs) make up a group of antioxidant enzymes. Cytochrome p450 (CYP) enzymes can influence oxidation and reduction reactions. We investigated the potential effects of GST and CYP enzymes in the pathogenesis of psoriasis. The study included 32 psoriasis patients and 22 healthy subjects. Psoriasis patients were administered 20 sessions of narrowband ultraviolet B phototherapy. Expressions of GST and CYP enzymes were assessed by immunohistochemical staining. Expression levels of GSTK1, GSTM1, and GSTT1 were significantly higher in psoriasis than in control tissues (P = 0.022, P = 0.001, and P = 0.006, respectively). Pre- and post-treatment expression was similar. Expression of CYP1A1 and CYP2E1 was significantly higher in pre- (P = 0.003 and P = 0.001, respectively) and post-treatment (P = 0.003 and P = 0.001, respectively) psoriatic tissues than in control tissues. No significant differences in CYP1B1 levels between the study and control groups were detected before treatment (P > 0.05). However, CYP1B1 levels were higher in post-treatment psoriatic tissue than in control tissue (P = 0.045). The significant increases in expression of GSTK1, GSTM1, and GSTT1 in psoriasis may reflect the increased activation of GST in response to excessive free radical formation from activated neutrophils or ultraviolet exposure to maintain antioxidant capacity in psoriasis. Furthermore, expressions of CYP1A1 and CYP2E1 represent important enzymatic systems in psoriasis. These findings suggest that psoriasis is an oxidative stress condition, although phototherapy does not affect these enzymatic systems. Further investigation is required.