Nordihydroguaiaretic acid and RHC 80267 potentiate astroglial injury during combined glucose-oxygen deprivation.
Membrane phospholipid degradation has been proposed to play a key role in hypoxic-ischemic brain injury. We tested the hypotheses that both nordihydroguaiaretic acid, a phospholipase A2 and lipoxygenase inhibitor, and RHC 80267, a diacylglycerol lipase inhibitor, would decrease the release of [3H]arachidonic acid metabolites from prelabeled cultures of astroglia subjected to combined glucose-oxygen deprivation and that these inhibitors would also decrease astroglial injury during combined glucose-oxygen deprivation. Both nordihydroguaiaretic acid and RHC 80267 significantly inhibited the release of [3H]arachidonic acid metabolites during combined glucose-oxygen deprivation. This suggests that two separate enzymic pathways, the phospholipase A2 pathway and the phospholipase C/diacylglycerol lipase pathway, contribute to the release of astroglial [3H]arachidonic acid metabolites during combined glucose-oxygen deprivation. However, both of these lipase inhibitors increased astroglial cell death during combined glucose-oxygen deprivation, probably due to inhibition of arachidonic acid release. We speculate that arachidonic acid release may be a mechanism of astroglial self-preservation during combined glucose-oxygen deprivation.
Haun
S E
SE
Wexner Institute for Pediatric Research, Children's Hospital, Columbus, OH 43205, USA.
Trapp
V L
VL
Clotz
M A
MA
Horrocks
L A
LA
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects*; D002478:Cells, Cultured; D003512:Cyclohexanones / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency*; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors*; D009637:Masoprocol / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D001095:Arachidonic Acids; D003512:Cyclohexanones; D011480:Protease Inhibitors; D009637:Masoprocol; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D007770:L-Lactate Dehydrogenase; D008071:Lipoprotein Lipase; D005947:Glucose