Increased DNA damage and oxidative stress in patients with cutaneous leishmaniasis

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. (c) 2005 Elsevier B.V. All rights reserved.