Respiratory tract infections and
pneumonia are major causes of morbidity and mortality in
burn victims, however, limited studies have examined the effects of
burn injury on airway epithelium. The current study examines the effect of scald
burn injury on rat tracheal epithelium at 5 days after injury and tests the hypothesis that treatment with
febuxostat (FBX), an inhibitor of
xanthine oxidase (XO), can be protective of cell homeostasis. Sprague Dawley rats were randomly divided into uninjured (
sham), injured (control) and injured and FBX treated groups, n = 8. Control and FBX treated groups received 60% total body surface area scald
burn injury. The FBX group received an i. p. dose (1 mg/kg) at 1 hour after injury and every 24 hours. At 5 days after injury, the animals were sacrificed and tracheal epithelial cell lysates were collected.
Malondialdehyde (MDA),
ATP, and XO activity were measured. Formation of 8-OHdG in tracheal epithelium was determined using immunohistochemistry (IHC) and immunoreactivity was quantitated. MDA levels were significantly increased in injured control animals (24.8 ± 2.3) compared to
sham (7.93 ± 1.2, p = 0.002). FBX treatment attenuated this response (12.6 ± 2.7, p = 0.02).
ATP levels were significantly decreased in control (0.7 ± 0.16) compared to
sham, (2 ± 0.14, p = 0.01).
ATP levels were increased with FBX treatment (1.8 ± 0.1, p = 0.03) compared to controls. There was a significant increase in XO activity in control animals, 1.04 ± 0.06 compared to
sham (0.34 ± 0.05, p = 0.03), and this response decreased with FBX treatment 0.46 ± 0.07 (p = 0.04). Immunolabeling of 8-OHdG in control animals was significantly increased (25.1 ± 0.7 compared to the
sham group 5.5 ± 1.9 (p = 0.01)), and was decreased with FBX treatment (7.0 ± 2.3 compared to control (p = 0.03)). The current study indicates that lipid peroxidation and
ATP depletion persist in tracheal epithelium for 5 days after injury along with increased XO activity and 8-OHdG. These effects were significantly attenuated by FBX treatment, suggesting that
reactive oxygen species generated by XO contribute to airway epithelial injury following scald
burn.