Akbulak Ozge, Karadag Ayse Serap, Akdeniz Necmettin, Ozkanli Seyma, Ozlu Emin, Zemheri Ebru, Oguztuzun Serpil
a Department of Dermatology , Istanbul Medeniyet University, School of Medicine, SB Goztepe Training and Research Hospital , Istanbul , Turkey.
b Department of Pathology , Istanbul Medeniyet University, School of Medicine, SB Goztepe Training and Research Hospital , Istanbul , Turkey.
Cutan Ocul Toxicol. 2018 Jun;37(2):180-185. doi: 10.1080/15569527.2017.1369431. Epub 2017 Oct 3.
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.
We aimed to evaluate the expressions of isoenzymes of GST and CYP families and the beneficial role of metotrexate (MTX) in this process.
This study included 21 patients with psoriasis and 22 healthy subjects. We treated all the patients with 10-15 mg/week of MTX for minimum 12 weeks. Expressions of GST and CYP enzymes were assessed by immunohistochemical staining.
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).
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.
氧化应激是氧化剂 - 抗氧化剂系统之间的失衡，可能在银屑病发病机制中起主要作用。细胞色素（CYP）是一类酶，负责各种内源性和外源性物质的代谢，如药物代谢。最重要的是，抗氧化系统是谷胱甘肽S - 转移酶（GST），它通过还原氧化产物来降低氧化应激。
我们旨在评估GST和CYP家族同工酶的表达以及甲氨蝶呤（MTX）在此过程中的有益作用。
本研究包括21例银屑病患者和22名健康受试者。我们对所有患者使用每周10 - 15毫克的MTX进行治疗，最短持续12周。通过免疫组织化学染色评估GST和CYP酶的表达。
银屑病组织中GSTK1、GSTM1和GSTT1的表达明显高于对照组织（分别为p < 0.05；p < 0.05；p < 0.05）。在银屑病患者中，GSTO1的表达与对照组相似。银屑病组织治疗前和治疗后CYP1B1和CYP2E1的表达明显高于对照组织（分别为p < 0.05；p < 0.05；p < 0.05；p < 0.05）。
我们发现GST或CYP的表达或组织水平显著增加，这在药物代谢和氧化应激中具有重要作用。MTX治疗导致临床症状明显改善，但我们发现MTX对这些参数没有任何显著影响。CYP2E1尤其对于MTX代谢是最重要的酶，因为它主要负责各种药物的毒性代谢。需要更多涉及大量患者和其他不同药物的实验研究来阐明氧化和抗氧化系统的作用以及银屑病发病机制的其他可能机制。
