Kocyigit Abdurrahim, Keles Huseyin, Selek Sahbettin, Guzel Salih, Celik Hakim, Erel Ozcan
Harran University, Medical Faculty, Department of Biochemistry, 63200 Sanliurfa, Turkey.
Mutat Res. 2005 Aug 1;585(1-2):71-8. doi: 10.1016/j.mrgentox.2005.04.012.
Cutaneous leishmaniasis (CL) is a chronic infectious and granulomatous disease caused by the Leishmania parasite that invades the skin. Reactive oxygen and nitrogen species (ROS and RNS) produced during an inflammatory response are an important part of host-defense strategies of organisms to kill the parasite. However, it is not well known whether these intermediates cause DNA damage in CL patients. We investigated the effect of Leishmania infection on basal levels of DNA strand breaks and on the oxidative/anti-oxidative status of patients with CL, and compared the data with those of healthy subjects. Twenty-five CL patients and 19 age- and sex-matched control subjects were enrolled in the study. We used the single-cell gel electrophoresis (also called comet assay) to measure DNA strand breaks in peripheral blood mononuclear leukocytes. Plasma protein carbonyl (PC), malondialdehyde (MDA) and total peroxide (TP) concentrations were measured to determine oxidative status and total anti-oxidative response (TAR) in plasma was measured to determine anti-oxidative status. The mean values of DNA damage and MDA and TP concentrations were significantly higher in CL patients than in the control group (p<0.001, p<0.01 and p<0.001, respectively). PC levels were also higher in patients, but this was not statistically significant (p>0.05). There was a significantly positive correlation between plasma MDA and DNA damage (r=0.524, p<0.01), and a negative correlation between TAR and TP levels (r=-0.790, p<0.001) in the patient group. These findings support the notion that ROS and RNS produced by the organism as a defense strategy may amplify the leishmanicidal activity in patients with CL. However, these intermediates not only cause the killing of the parasite but also induce oxidative damage in non-infected cells. Therefore, these patients must be treated urgently to counteract the oxidative DNA damage.
皮肤利什曼病（CL）是一种由利什曼原虫侵入皮肤引起的慢性感染性肉芽肿疾病。炎症反应过程中产生的活性氧和氮物种（ROS和RNS）是生物体宿主防御策略中杀死寄生虫的重要组成部分。然而，这些中间产物是否会导致CL患者的DNA损伤尚不清楚。我们研究了利什曼原虫感染对CL患者DNA链断裂基础水平以及氧化/抗氧化状态的影响，并将数据与健康受试者进行了比较。本研究纳入了25例CL患者和19例年龄及性别匹配的对照受试者。我们使用单细胞凝胶电泳（也称为彗星试验）来测量外周血单核白细胞中的DNA链断裂情况。测量血浆蛋白羰基（PC）、丙二醛（MDA）和总过氧化物（TP）浓度以确定氧化状态，并测量血浆中的总抗氧化反应（TAR）以确定抗氧化状态。CL患者的DNA损伤、MDA和TP浓度的平均值显著高于对照组（分别为p<0.001、p<0.01和p<0.001）。患者的PC水平也较高，但无统计学意义（p>0.05）。患者组中血浆MDA与DNA损伤之间存在显著正相关（r=0.524，p<0.01），TAR与TP水平之间存在负相关（r=-0.790，p<0.001）。这些发现支持了这样一种观点，即生物体作为防御策略产生的ROS和RNS可能会增强CL患者的杀利什曼原虫活性。然而，这些中间产物不仅会导致寄生虫的死亡，还会在未感染的细胞中诱导氧化损伤。因此，必须紧急治疗这些患者以对抗氧化性DNA损伤。
