Mechanisms of hippocampal reoxygenation injury.
Mechanisms of 12 min of hypoxia and subsequent reoxygenation were studied in rat hippocampal slices. General cell injury in reoxygenation was indicated by increased lactate dehydrogenase (LDH). Increase in conjugated dienes (CD) showed that oxygen radical burst induced lipid peroxidation (LPO). ATP increase was also involved in reoxygenation injury, since cyanide, an inhibitor of ATP synthesis, decreased this damage. The results obtained on using inhibitors of oxygen radicals generation, i.e., allopurinol, indomethacin, rotenone, and antimycin A, strongly suggest that the sources of oxygen radicals were the xanthine/xanthine oxidase system, prostaglandin synthesis, and mitochondrial respiratory chain. The involvement of oxygen radicals in oxidative stress was confirmed also by using chain-breaking antioxidants, trolox alpha-tocopherol and stobadine, [(-)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido (4,3b)indole]. Stobadine added at the onset of reoxygenation was most effective, acting in a dose-dependent manner and found to be without effect when applied in hypoxia. Cytochrome-c oxidase was decreased in reoxygenated hippocampal slices treated with stobadine.
Horáková
L
L
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dúbravská, Bratislava, Slovak Republic. exfahorl@savba.savba.sk
Stolc
S
S
Chromíková
Z
Z
Pekárová
A
A
Derková
L
L
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D000493:Allopurinol; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV; D007213:Indomethacin