Mechanisms of hippocampal reoxygenation injury. Treatment with antioxidants.
The effects of hypoxia of different durations (8, 12 or 15 min) and of subsequent reoxygenation were studied in rat hippocampal slices by measuring enzyme activities related to oxidative stress: superoxide dismutase (SOD), cytochrome c oxidase and lactate dehydrogenase (LDH). Simultaneously the degree of lipid peroxidation was estimated by measuring conjugated dienes (CD). Reoxygenation after 8-min of hypoxia induced general cell injury indicated by increased LDH activity. Reoxygenation after 12-min of hypoxia started lipid peroxidation assessed by an increase in CD, and after 15-min of hypoxia followed by reoxygenation CD were found to be significantly decreased, suggesting lipid degradation. The injury induced by a hypoxia of 12 min and reoxygenation was reduced by SOD and catalase, indicating that oxygen radicals were involved in this process. The oxygen radicals originating from the xanthine/xanthine oxidase system, from the synthesis of prostaglandins, as well as from the mitochondrial respiratory chain, since allopurinol, indomethacin and rotenone decreased while antimycin increased reoxygenation injury. An increase in ATP may also have been involved as cyanide, an inhibitor of ATP synthesis, decreased the reoxygenation injury. The chain-breaking antioxidants trolox, alpha tocopherol and the pyridoindole stobadine were effective in preventing reoxygenation injury, indicating the involvement of lipid peroxidation in this process.
Horáková
L
L
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Stolc
S
S
Chromíková
Z
Z
Pekárová
A
A
Derková
L
L
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002243:Carbolines / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000378:metabolism; D006624:Hippocampus / Q000503:physiopathology*; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000627:therapeutic use; D014969:Xanthine Oxidase / Q000378:metabolism
D000975:Antioxidants; D002243:Carbolines; D016861:Cyclooxygenase Inhibitors; D014810:Vitamin E; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D003576:Electron Transport Complex IV; C100106:dicarbine