Freitas J P, Filipe P, Yousefi A, Emerit I, Guerra Rodrigo F
Department of Dermatology, Hospital de Santa Maria, Lisboa, Portugal.
Dermatology. 1998;197(4):343-8. doi: 10.1159/000018029.
Adamantiades-Behçet's disease is a chronic systemic disorder associating oral and genital ulcerative lesions with ocular and cutaneous manifestations. Previous publications report increased superoxide production by neutrophils and macrophages, increases in cytokines and malondialdehyde (MDA), as well as low levels of enzymatic antioxidant defenses.
We looked for another marker of oxidative stress in Adamantiades-Behçet's disease: the presence of clastogenic factors (CF) in patients' plasma. In addition, we determined plasma endproducts of lipid peroxidation (MDA).
We studied 20 patients and 20 controls. The clastogenic activity was evaluated by means of cytogenetic methods. This test (CF test) detects circulating prooxidants, due to their clastogenic effects after exposure of lymphocyte cultures of healthy persons to plasma ultrafiltrates from patients. The clastogenic prooxidants are lipid peroxidation products and cytokines, in particular TNF-alpha. Lipid peroxidation was evaluated by the Yagi method.
The CF test was positive in 18 out of 20 patients, while it was negative in all 20 control persons. The mean increase in chromosomal breaks was 10.6 +/- 3.8 in cultures exposed to patients' plasma and 1.3 +/- 2.4 for cultures receiving control plasma (p <0.001). The clastogenic effect of patients' plasma ultrafiltrates was significantly inhibited by superoxide dismutase (EC 1.15.1.1), suggesting an important role of the superoxide radical in the clastogenic pathway. Thiobarbituric-acid-reactive substances (expressed as nanomoles MDA per milliliter) were also significantly increased in these patients: 10.6 +/- 3.2 for patients and 6.6 +/- 1.4 for controls (p <0.001).
The presence of CF in the plasma of patients, indicating the presence of circulating prooxidants with chromosome-damaging effects, confirms an oxidative stress in Adamantiades-Behçet's disease. The anticlastogenic effect of superoxide dismutase in vitro suggests the implication of the superoxide radical. MDA levels were also significantly increased in patients.
白塞病是一种慢性全身性疾病,伴有口腔和生殖器溃疡性病变以及眼部和皮肤表现。既往文献报道中性粒细胞和巨噬细胞产生超氧化物增加、细胞因子和丙二醛(MDA)升高,以及酶抗氧化防御水平降低。
我们在白塞病中寻找氧化应激的另一种标志物:患者血浆中致断裂因子(CF)的存在。此外,我们测定了脂质过氧化的血浆终产物(MDA)。
我们研究了20例患者和20例对照。通过细胞遗传学方法评估致断裂活性。该试验(CF试验)可检测循环中的促氧化剂,因为健康人的淋巴细胞培养物暴露于患者血浆超滤物后会产生致断裂作用。致断裂促氧化剂是脂质过氧化产物和细胞因子,特别是肿瘤坏死因子-α。通过矢木法评估脂质过氧化。
20例患者中有18例CF试验呈阳性,而所有20例对照者均为阴性。暴露于患者血浆的培养物中染色体断裂的平均增加数为10.6±3.8,接受对照血浆的培养物为1.3±2.4(p<0.001)。超氧化物歧化酶(EC 1.15.1.1)可显著抑制患者血浆超滤物的致断裂作用,提示超氧阴离子在致断裂途径中起重要作用。这些患者中硫代巴比妥酸反应性物质(以每毫升纳摩尔MDA表示)也显著增加:患者为10.6±3.2,对照为6.6±1.4(p<0.001)。
患者血浆中存在CF,表明存在具有染色体损伤作用的循环促氧化剂,证实白塞病存在氧化应激。超氧化物歧化酶在体外的抗致断裂作用提示超氧阴离子参与其中。患者的MDA水平也显著升高。