Investigation of oxidative damage during attack period in familial mediterranean fever patients

Familial Mediterranean Fever (FMF) is an autosomal recessive genetic disorder characterized by recurrent febrile inflammatory episodes of the serous and synovial membranes. There is a massive influx of neutrophils into the serosal sites during the acute phase of the disease. There is also an inappropriate and prolonged response to inflammatory stimuli. It is known that ?oxidative burst? caused by persistently activated neutrophils may create oxidative damage in cellular macromolecules. The aim of this study is to investigate the level of oxidative stress and antioxidant capacity which are thought to be important in the inflammatory pathway during attack period in FMF patients.The study group is composed of 15 patients and 17 healthy volunteer adults. Venous blood were collected two times from all the patients. Lipid peroxidation, protein oxidation, DNA base damage and antioxidant compounds were investigated in patient and control groups. Significantly increased plasma levels of malondialdehyde (MDA) was observed in the patient group with attack period compared to control group and to the attack-free period of same patient group (p=0,000 and p=0,005, respectively). The level of 2,6-diamino-5-formamidopyrimidine (FapyG) in DNA, which is the typical product of oxidative damage to DNA bases, was found to be significantly greater in the patient group with attack and attack-free periods than in the control group (p=0,000 and p=0,002, respectively). The level of 8-hydroxydeoxyguanin (8-OH-dG) as another product of oxidative damage to DNA bases was higher in patients with attack than controls (p=0,01). The concentrations of plasma nitrotyrosine and nitric oxide (NO) were significantly elevated in control group than patients (p=0,000 and p=0,002,respectively). Superoxide dismutase (SOD) and glutathione (GSH, GSSG) levels were similar in all groups.Our results suggest that the elucidation of the damage to cellular macromolecules resulting from oxidative stress may help understand the pathogenesis of FMF.In conclusion, we showed, for the first time, the accumulation of some products of oxidative damage to DNA in polimorphonuclear leucocytes of FMF patients in attack period. This work suggests that the persistent activation of neutrophils may be the cause of accumulation of DNA damage and lipid peroxidation products due to excess production of free radicals. These cells in FMF patients may also be defective in repair of oxidatively induced lesions in their geneomic DNA because of mutations in MEFV gene.