Brain superoxide anion generation in asphyxiated piglets and the effect of indomethacin at therapeutic dose

Massroor Pourcyrous, Charles Leffler, Henrietta S. Bada, Sheldon B. Korones, David W. Busua

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Abstract

We have previously shown that generation of superoxide anion occurs in cerebral cortex during as-phyxia/reventilation in newborn pigs and that a high dose of indomethacin (5 mg/kg i.v.) abolishes superoxide anion production. The purposes of this study were 1) to determine whether the generation of superoxide anion occurs primarily during asphyxia or whether rcventilation must take place, 2) to investigate the effects of indomethacin prctreat-ment at a therapeutic dose of 0.2 mg/kg i.v. on superoxide anion generation, and 3) to investigate the effects of oxypurinol, an oxygen free radical scavenger, on superoxide anion production during asphyxia/reventilation. Superoxide anion production on cerebral cortex was determined by superoxide dismutase-inhibitable nitroblue tetrazolium (NBT) reduction using closed cranial windows. Superoxide anion generation during asphyxia without rcventilation was 4 ± 2 pmol NBT/mm2 per 20 min, which was significantly lower than during asphyxia/reventilation (16 ±4 pmol NBT/mm2 per 20 min) but comparable to the control group (3 ± 1 pmol NBT/mm2 per 20 min). Indomethacin given at therapeutic dosage before asphyxia/reventilation decreased superoxide anion production to 3 ± 1 pmol NBT/mm2 per 20 min, values not significantly different from the control group and from piglets pretreated with oxypurinol at a dose of 50 mg/kg i.v. (4 ± 2 pmol NBT/mm2 per 20 min). We conclude that in newborn pigs 1) superoxide anions are generated largely during rcventilation rather than during asphyxia; 2) the therapeutic dose of indomethacin (0.2 mg/kg) is effective in inhibiting the superoxide anion generation during asphyxia/reventilation; and 3) oxypurinol reduces the superoxide anion accumulation on cerebral cortex during asphyxia/reventilation.

Original languageEnglish (US)
Pages (from-to)366-369
Number of pages4
JournalPediatric Research
Volume34
Issue number3
DOIs
StatePublished - Jan 1 1993

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Superoxides
Indomethacin
Asphyxia
Nitroblue Tetrazolium
Brain
Oxypurinol
Therapeutics
Cerebral Cortex
Swine
Control Groups
Free Radical Scavengers
Superoxide Dismutase
Reactive Oxygen Species

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

Brain superoxide anion generation in asphyxiated piglets and the effect of indomethacin at therapeutic dose. / Pourcyrous, Massroor; Leffler, Charles; Bada, Henrietta S.; Korones, Sheldon B.; Busua, David W.

In: Pediatric Research, Vol. 34, No. 3, 01.01.1993, p. 366-369.

Research output: Contribution to journalArticle

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