Biological markers of oxidative stress in progressive muscular dystrophies: A preliminary study: 157

Background/Aims. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are fatal degenerative disorders of muscle resulting from mutations in the gene coding for dystrophin. The exact mechanisms through which the absence or an abnormal dystrophin result in muscle degeneration are still uncertain. Oxidative-damage may play a key role in these processes as the neuronal isoform of nitric oxide (NO) synthase, is associated with dystrophin-glycoprotein complex (DGC). Dystrophin abnormalities may lead to an impaired NO production with inadequate NO-mediated protection against ischemia and damaging actions of the reactive oxygen free radical species (ROS). The aim of the study was to evaluate plasma levels of isoprostanes, a sensitive biological marker of oxidative stress, in patients affected by DMD and BMD. Methods. Twenty nine patients with age ranging from 14 months to 30 years entered the study. In all patients clinical diagnosis was confirmed by molecular analysis. Isoprostanes were assayed in all patients by collecting blood samples with butylated hydroxytoluene to prevent oxidation during processing. Results. When globally evaluated, serum levels of isoprostanes were found significantly higher in patients than the normal ranges. In particular, wheel-chaired patients with Duchenne muscular dystrophy with ages ranging from 12 years to 16 years, seemed to have the highest plasma levels of isoprostanes. Discussion/Conclusions. ROS are ubiquitously produced during normal aerobic cellular metabolism, with the possibility of initiating damage to lipids, protein, and nucleic acids. A protective role against ROS actions in muscle fibres is played by the DGC. In this context, pathogenetic defects in the DGC mainly have two biochemical consequences: An impaired NO(*) production, which determines a scarce protection of muscle cells against ischemia, and an increased cellular susceptibility to metabolic stress. This pathogenetic model has been called the 'two-hit' hypothesis. In the present study we first reported on the preliminary data regarding the evaluation of isoprostanes plasma level, a sensitive oxidative stress marker, in a series of patients with progressive muscular dystrophies. Isoprostanes resulted higher than the normal range values. In particular, the most severely affected DMD patients showed the highest levels of oxidative stress marker. Unfortunately, the present sample size was nor sufficiently large in number to allow correlation studies between isoprostanes levels and specific clinical/bichemical findings such as the type of muscular distrophy (DMD or BMD) and serum CPK levels. Nevertheless, our ongoing study and previous experimental studies seem to suggest that the increased markers of oxidative stress we found might be the plasmatic expression of the degenerative processes occurring in muscles. Of course, the possibility that oxidative stress might be induced by myoglobin (a Fe-containing protein) released in the blood of these patients, cannot be ruled out at this stage.