Effect of stobadine on brain lipid peroxidation induced by incomplete ischemia and subsequent reperfusion.
The ability of stobadine (ST) to prevent lipid peroxidation was tested in incomplete rat cerebral ischemia induced by 4 hour ligation of the common carotid arteries with a subsequent 10 min reperfusion. The extent of lipid peroxidation was determined by the measurement of the level of conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS). The levels of CD and TBARS were significantly elevated in brain cortex samples from animals subjected to ischemia followed by reoxygenation in comparison with ischemic samples without reperfusion, samples from sham operated or control animals. The concentration of CD and TBARS significantly decreased in animals treated with therapeutic doses of ST (2 mg/kg) administered i.v. immediately before reperfusion or 10 min after the onset of reperfusion. Stobadine was more effective than the known lipid antioxidant vitamin E, given in a dose of 30 mg/kg.day i.m. over 3 consecutive days prior to ischemia. The beneficial effect of ST on survival of rats was more effective in comparison with vitamin E. Significant changes were found in the activities of the antioxidative enzymes, i.e. increase in superoxide dismutase (SOD) and decrease in glutathione peroxidase (GP) in brain cortex samples from animals subjected to ischemia followed by reoxygenation. Stobadine prevented these changes. Catalase (CAT) activity was not detectable. It may be concluded from the increased SOD activity that oxygen radicals play a significant role in cerebral ischemia followed reperfusion. In addition to its antioxidant effect, stobadine probably prevents superoxide radical generation. The mechanism of xanthine oxidase inhibition is not involved in preventing superoxide radical generation by stobadine. Stobadine maintained high GP activity, probably by preventing glutathione oxidation.
Horáková
L
L
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, CSFR.
Uraz
V
V
Ondrejicková
O
O
Lukovic
L
L
Juránek
I
I
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D002243:Carbolines / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015424:Reperfusion; D013858:Thiobarbiturates / Q000737:chemistry; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D002243:Carbolines; D013858:Thiobarbiturates; D014810:Vitamin E; C029684:thiobarbituric acid; C100106:dicarbine