Effect of cyclooxygenase inhibition on brain cell membrane lipid peroxidation during hypoxia in newborn piglets.
To test the hypothesis that indomethacin, an inhibitor of cyclooxygenase, reduces free radical-induced brain cell membrane changes during cerebral hypoxia, we determined levels of brain cell membrane lipid peroxidation products and Na+,K(+)-ATPase activity as indicators of free radical production and membrane function, respectively, in 29 newborn piglets divided into 4 groups. Eight saline- and 4 indomethacin-treated normoxic animals served as controls; 8 saline-pretreated piglets and 9 piglets pretreated with indomethacin were exposed to hypoxic hypoxia for 60 min. Cerebral hypoxia was documented using 31P-NMR spectroscopy. In saline-pretreated hypoxic animals Na+,K(+)-ATPase activity decreased significantly and levels of membrane lipid peroxidation products increased significantly compared to normoxic controls. Indomethacin pretreatment prevented the hypoxia-induced increase in membrane lipid peroxidation products but had no effect on the decrease in Na+,K(+)-ATPase activity. Thus the apparent reduction in free radical production by indomethacin pretreatment did not prevent the hypoxia-induced change in Na+,K(+)-ATPase activity.
McGowan
J E
JE
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia.
McGowan
J C
JC
Mishra
O P
OP
Delivoria-Papadopoulos
M
M
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure*; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005609:Free Radicals / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013552:Swine
D016861:Cyclooxygenase Inhibitors; D005609:Free Radicals; D000254:Sodium-Potassium-Exchanging ATPase; D007213:Indomethacin