Effect of 7-nitroindazole on bilirubin-induced changes in brain cell membrane function and energy metabolism in newborn piglets.
We evaluated the effects of 7-nitroindazole, a selective neuronal nitric oxide synthetase (nNOS) inhibitor, on bilirubin-induced alterations in brain cell membrane function and energy metabolism in the newborn piglets. The decreased cerebral cortical cell membrane Na(+),K(+)-ATPase activity and increased lipid peroxidation products, indicative of bilirubin-induced brain damage, were significantly attenuated by 7-nitroindazole treatment. 7-Nitroindazole also significantly improved the bilirubin-induced reduction in both brain ATP and phosphocreatine levels, decreased blood-to-brain glucose ratio and increased brain lactate level. In summary, 7-nitroindazole significantly attenuated the bilirubin-induced alterations in brain cell membrane function and energy metabolism in the newborn piglet. These findings suggest that nitric oxide produced by nNOS is involved in mediating or facilitating bilirubin-induced cerebral dysfunction.
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Won Soon
WS
Park
Yun Sil
YS
Chang
Munhyang
M
Lee
D000818:Animals; D000831:Animals, Newborn; D001663:Bilirubin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D004347:Drug Interactions; D004734:Energy Metabolism / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology*; D007647:Kernicterus / Q000188:drug therapy / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D011897:Random Allocation; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D018709:Statistics, Nonparametric; D013552:Swine
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007191:Indazoles; D019344:Lactic Acid; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D001663:Bilirubin; C080122:7-nitroindazole