Prevention of postasphyxial increase in lipid peroxides and retinal function deterioration in the newborn pig by inhibition of cyclooxygenase activity and free radical generation.
Free radicals have been implicated in the development of injury to the immature retina. Asphyxia increases free radicals as well as prostaglandins (PG) in neural tissues. We assessed whether in the retina the cyclooxygenase pathway contributes to free radical formation after oxidative insults such as asphyxia, which in turn disrupts retinal function. Newborn pigs were treated with either saline, ibuprofen (194 mumol/kg i.v.), or allopurinol (1 mmol/kg i.v.), and retinal malondialdehyde (MDA), hydroperoxides, PGE2 and PGF2 alpha levels, and the amplitudes and implicit times of the a- and b-waves of the full-field electroretinogram were measured before and 1 h after a 5-min period of asphyxia. In saline-treated animals, asphyxia caused a marked increase (p < 0.01) in MDA, hydroperoxides, PGE2, and PGF2 alpha concentrations in the retina. This was associated with a significant decrease (p < 0.01) in the b-wave amplitude measured under scotopic and photopic conditions and an increase in the b-wave implicit times. Ibuprofen and another cyclooxygenase inhibitor, indomethacin (28 mumol/kg i.v.), decreased PGE2 and PGF2 alpha levels and prevented the increase in MDA and hydroperoxides after asphyxia. Allopurinol maintained low concentrations of MDA and hydroperoxides after asphyxia. Both ibuprofen and allopurinol prevented the postasphyxial changes in the b-wave amplitude and diminished the delay in implicit time observed after asphyxia in saline-treated pigs. Our findings suggest that in the retina after asphyxia free radicals appear to originate primarily from the cyclooxygenase pathway and contribute to the deterioration in retinal electrophysiologic function of the newborn animal. Cyclooxygenase inhibitors, like free radical scavengers, may protect retinal function from deteriorating after oxidative stresses.
Chemtob
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Department of Pediatrics, Hôpital Ste. Justine, Montreal, Quebec, Canada.
Roy
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MS
Abran
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Fernandez
H
H
Varma
D R
DR
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004596:Electroretinography; D005609:Free Radicals; D007052:Ibuprofen / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology; D013552:Swine
D005609:Free Radicals; D008054:Lipid Peroxides; D008315:Malondialdehyde; D000493:Allopurinol; D015237:Dinoprost; D015232:Dinoprostone; D007052:Ibuprofen