Increase in oxidative damage to lipids and proteins in skeletal muscle of uremic patients.

Muscle weakness and reduced exercise capacity are frequent complaints of patients with chronic uremia. Several lines of evidence have suggested that chronic uremia result in a state of increased oxidative stress. Reactive oxygen species (ROS) and free radicals are capable of damaging lipids and proteins but it remains unclear whether oxidative damage plays a role in the skeletal myopathy commonly seen in chronic uremia. In this cross-sectional study, we compared the levels of oxidative damage to proteins and lipids of skeletal muscle from 40 chronic uremic patients and 20 age- and sex-matched healthy subjects. Protein carbonyls were determined by a spectrophotometric method to assess the oxidative damage to proteins. Our results showed that the mean content of protein carbonyls in skeletal muscles was significantly elevated in the hemodialysis patients (3.78+/-0.14 nmol of 2,4-dinitrophenyl-hydrazone per mg of protein) as compared to healthy controls (2.97+/-0.28 nmol per mg of protein, p = 0.017 vs normal controls). In addition, we found that the mean malondialdehyde (MDA) level was also significantly increased in the uremic patients compared to healthy controls. Further analysis revealed that there was an age-dependent increase in both oxidative damages in these patients. Regression analysis between plasma protein carbonyl and MDA levels showed a significant correlation between these two parameters (r = 0.43, p = 0.002). The finding of increased oxidative damage to protein and lipids provide support that oxidative damage may play a role in the pathogenesis of skeletal myopathy in chronic uremic patients on hemodialysis.