Allopurinol inhibition of neutrophilic alveolar response during hyperoxia

Allopurinol is a potent xanthine oxidase inhibitor that has been administered to animals to protect tissues from oxidant injury. We hypothesized that allopurinol may protect against oxidant injury by inhibiting the inflammatory response. Male Sprague-Dawley rats were injected daily with vehicle or allopurinol and compared with noninjected controls. Animals were exposed to room air or 90% oxygen for 14 days. At the end of the exposure period, all animals were lavaged and bronchoalveolar lavage fluid (BALF) was examined for cell counts, lactate dehydrogenase (LDH), and protein. BALF neutrophils were significantly increased in oxygen-exposed noninjected controls (33 ± 7 x 10³/mm³) and also in the vehicle- inoculated oxygen-exposed animals (43 ± 6 x 10³/mm³). Allopurinol treatment resulted in a decrease in the neutrophilic alveolar response in oxygen-exposed animals (5.3 ± 4 x 10³/mm³, P < 0.001). These data reveal that oxygen exposure produces a neutrophilic alveolar response that is attenuated by allopurinol treatment. BALF protein and LDH were significantly increased in all inoculated and noninoculated oxygen-exposed animals compared with air-exposed animals. Therefore, allopurinol decreases the neutrophilic alveolar response produced by a hyperoxic exposure in the rat but does not decrease lung injury as assessed by alveolar LDH and protein release.