Dapsone hydroxylamine-mediated alterations in human red blood cells from endometriotic patients

Abstract

Endometriosis, an estrogen-dependent chronic gynecological disease in women of reproductive age, is characterized by a systemic inflammation status involving also red blood cells (RBCs). In this study, we evaluated how the protein oxidative status could be involved in the worsening of RBC conditions due to dapsone intake in endometriotic women in potential treatment for skin or infection diseases. Blood samples from two groups of volunteers, control group (CG) and endometriosis patient group (PG), were analyzed for their content of band 3 tyrosine phosphorylation (Tyr-P) and high molecular weight aggregate (HMWA) in membranes, and glutathione (GSH) content and carbonic anhydrase (CA) activity in cytosol. In endometriotic patients, RBC showed the highest level of oxidative-related alterations both in membrane and cytosol. More interestingly, the addition of dapsone hydroxylamine (DDS-NHOH) could induce further increase of both membranes and cytosol markers, with an enhancement of CA activity reaching about 66% of the total cell enzyme amount. In conclusion, in PG the systemic inflammatory status leads to the inability of counteracting adjunctive oxidative stress, with a potential involvement of CA-related pathologies, such as glaucoma. Hence, the importance of the evaluation of therapeutic approaches worsening oxidative imbalance present in PG RBC is underlined.

Chinese abstract

子宫内膜异位症是好发于育龄期女性的慢性雌激素依赖性疾病, 其特点是红细胞（RBCs）参与的全身性炎症反应。本研究主要目的为评估蛋白质氧化状态是如何参与并恶化应用氨苯砜治疗皮肤或感染性疾病的子宫内膜异位症患者的红细胞状态。血液样本来自于对照组（CG）人群和内异症组（PG）患者, 分析样本红细胞膜中红细胞膜带 3蛋白酪氨酸的磷酸化水平（Tyr-P）和高分子电泳条带（HMWA）, 分析样本红细胞胞质中谷胱甘肽（GSH）含量和碳酸酐酶（CA）水平。结果表明：内异症组样本的红细胞膜和胞质溶胶的氧化相关改变程度最高；更值得注意的是, 加入羟胺氨苯砜（DDS-NHOH）后红细胞膜和胞质溶胶的标记物含量进一步增加, 同时伴随着碳酸酐酶活性增加, 约达到细胞总酶量的66%。 综上, 内异症组的全身性炎症状态会导致其无法抵抗额外的氧化应激反应, 并引发潜在的碳酸酐酶相关性疾病如青光眼。因此, 需更加注重对内异症治疗方案是否会加重患者红细胞氧化不平衡状态的评估。

Keywords:

• Endometriosis
• dapsone
• DDS-NHOH
• red blood cells
• oxidative stress

Disclosure statement

Authors have no conflict of interest.

Additional information

Funding

This work was supported by the ex 60% funds [60A07-4573/10].