DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity

Quality of Life in Family Members of Vitiligo Patients: A Questionnaire Study in Saudi Arabia

Many dermatologic disorders are known to adversely affect quality of life (QoL) in close relatives or partners of patients; however, it is unknown whether vitiligo impacts the QoL of family members.The aim of this study was to identify the level and domains in which the QoL of partners/relatives of patients with vitiligo are affected by the disease.A total of 141 patients with vitiligo, along with their family members, were recruited to complete validated QoL questionnaires, including the Dermatology Life Quality Index (DLQI) and the Family Dermatology Life Quality Index (FDLQI).Family member QoL was affected in 129 (91.5 %) of subjects. Mean FDLQI score was 10.3 ± 6.4 standard deviation. Higher FDLQI score (greater impairment in QoL) was significantly associated with male patients, a shorter duration of disease, and higher educational levels in family members. The most affected FDLQI items in order of decreasing incidence were emotional impact, burden of care, impact on the physical well-being of the family member, problems due to the reaction of others in response to the patient’s skin appearance and effect on social life. Overall FDLQI score and the number of items affected correlated with overall patient DLQI score (p < 0.001, r = 0.56 and p < 0.001, r = 0.53, respectively).Vitiligo has a major impact on the QoL of family members of patients and often significantly impairs many aspects of their lives. Educational and supportive programs are recommended for family members of vitiligo patients who are at an increased risk for QoL impairments