Chromossome instability in asthma – an antioxidant treatment as a possible pharmacological strategy?

Asthma is one of the most common respiratory diseases, with airway inflammation as the most prominent pathological feature. Although originally believed to be a single disease, it is now recognized as a complex of multiple phenotypes, with different degrees of severity and treatment responses. The severe inflammatory state becomes apparent when reactive oxygen species overwhelm the antioxidant defense. Thus the oxidant-antioxidant imbalance plays an important role in airway inflammation. It is well documented the role of oxidative stress (OS) in the increase of chromosome instability (CI), and, consequently, in cancer predisposition. So it is important to carry out studies in order to establish limits for harmful effects with carcinogenic potential.

The aim of this study was to evaluate cellular levels of OS-related CI in asthma patients and the possible protective effect of antioxidants. For that purpose, spontaneous and 1,2,3,4-diepoxybutane (DEB)-induced lymphocyte cultures from patients with mild and severe asthma were performed. Lymphocyte cultures from healthy donors, at the same conditions, were used as control. Antioxidant-enriched (N-Acetylcysteine+α-lipoic acid) lymphocyte cultures from severe patients were posteriorly performed. A hundred metaphases per culture were scored in order to estimate the relative frequency of CI.

Our results showed that lymphocytes from severe asthma patients had a significant increase of CI, both in spontaneous and DEB-induced cultures. However, in lymphocytes from mild asthma patients there were no significant differences compared to controls. This suggests that in patients with severe asthma, subjected to extreme OS conditions, a possible genotoxic effect may occur at the cellular level. When the lymphocytes from these patients were subjected to an antioxidant treatment, a significant and consistent decrease in levels of CI was observed.

Understanding how CI due to exposure to OS correlates to asthma patients clinical characteristics may be pivotal to the design of preventive measures or patient-specific treatments.