HYPERBILIRUBINEMIA RESULTS IN REDUCED OXIDATIVE INJURY IN NEONATAL GUNN-RATS EXPOSED TO HYPEROXIA

Bilirubin is a potent antioxidant in vitro. To determine whether bilir ubin also is an antioxidant in vivo, we studied markers of oxidative i njury in the Gunn rat model exposed to hyperoxia. Homozygous jaundiced males were mated with heterozygous nonjaundiced females to obtain bot h jaundiced and nonjaundiced pups within a litter. Once delivered, the pups and their mother were placed in air (21% O-2) or hyperoxia (> 95 % O-2) for 3 d. Both jaundiced and nonjaundiced pups were removed from the chambers daily. Animals were sacrificed and blood was drawn for d etermination of serum bilirubin, blood thiobarbituric acid-reactive su bstances (TEARS) by fluorescence assay, serum hydroperoxides, and seru m protein oxidation. Tissues (liver, lung, and brain) were assayed for lipid peroxides (TEARS, conjugated dienes [CD], loss of polyunsaturat ed fatty acid content [PUFA]). We also measured a wide range of serum antioxidants including superoxide dismutase, catalase, glutathione, vi tamins A, C, and E, and uric acid. Blood TEARS were significantly decr eased in the jaundiced pups compared to the nonjaundiced pups on day 3 of hyperoxia, and blood TEARS were inversely correlated to serum bili rubin on day 3 of hyperoxia (R(2) = .89). Similar decreases in serum l ipid hydroperoxides and serum protein carbonyl content were detected i n the jaundiced pups as compared to their nonjaundiced littermates. Ot her serum antioxidants were not increased in jaundiced animals compare d to nonjaundiced animals. Relative lung weight was lower in jaundiced pups exposed to hyperoxia compared to similarly exposed nonjaundiced pups, suggesting a reduction in hyperoxia-induced lung edema. We detec ted no significant effects of bilirubin on parameters of lipid peroxid ation in solid tissues. We conclude that serum bilirubin protects agai nst serum oxidative damage in the first days of life in neonatal Gunn rats exposed to hyperoxia. We speculate that bilirubin is a functional ly important transitional antioxidant in the circulation of human neon ates and that it may be involved in modulation of injury due to hypero xia.