Relationship Between Oxidative Stress and Chromosomal Damage in Patients with Chronic Diseases

Abstract Chronic non-communicable diseases are identified by the prolonged imbalance in the production of reactive oxygen species and antioxidant defense mechanism. Reactive species can directly attack DNA, and if there are no repairs of the lesions, these can lead to the identification of chromosomal damage, which is a well-established indicator of genomic stability and cancer risk. There is less data related to this relationship in the context of Iraq. The aim of the study was to examine the oxidative stress evaluation and chromosomal damage among patients with type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD) and essential hypertension admitted at Al-Hussein Teaching Hospital from Al-Samawah city of Iraq. A case-control study was undertaken on 120 patients (40 T2DM, 40 non-dialysis CKD stages 3-4 and 40 essential hypertension patients), as well as on 40 control patients matched by age and sex. The study determined the level of serum malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), reduced glutathione (GSH), and activity of superoxide dismutase (SOD). The designed oxidative stress index (OSI) was also calculated. Chromosomal damage was evaluated among cultured peripheral blood lymphocytes using the metaphase chromosomal aberration (CA) technique and the cytokinesis-block micronucleus (CBMN) method. Findings: All patient groups showed higher amounts of MDA, TOS and OSI and lower amounts of TAC, GSH and SOD than controls (p < 0.001), most notably in CKD. The frequency of total CA (CKD 4.5 ± 1.4%, T2DM 3.6 ± 1.2%, hypertension 2.8 ± 1.0% vs 1.2 ± 0.6% in controls) and micronuclei (18.2, 14.9 and 12.1 vs 6.8 per 1000 binucleated cells respectively) was significantly increased (p < 0.001). In the overall study group, OSI showed a direct correlation with the frequency of micronuclei (r = 0.66) as well as the frequency of CA (r = 0.59) and an inverse correlation with TAC (r = − − -0.49 and -0.43). After adjustment for age, sex, smoking, BMI and the duration of the disease OSI remained the strongest independent factor for the frequency of micronuclei in patients (β = 0.41, p < 0.001). Oxidative stress is highly correlated with chromosomal defects in patients suffering from chronic diseases. Routine evaluation of oxidative stress as well as cytogenetic indicators may facilitate the identification of patients in whom the probability of genome instability is the highest. Keywords: oxidative stress; chromosomal aberrations; micronucleus; malondialdehyde; total antioxidant capacity; type 2 diabetes mellitus; chronic kidney disease; hypertension; Iraq