[Comparison of the antihypoxic and antioxidant properties of aminothiol and triazinoindole derivatives].
The antihypoxic activity of six aminothiol and triazinoindole derivatives was studied on a model of hypobaric (hypoxic) hypoxia in rats. With respect to the antihypoxic activity, the compounds can be arranged in the following order: amtizole succinate = amtizole approximately equal to gutimine > T-475 > gutimine > succinate succinate. One of the possible mechanisms of action for all antyhypoxants is the inhibition of lipid peroxidation and recovery of hypoxia-induced antioxidant defense system in the brain, kidneys, liver, myocardium, and muscles, which results in reduction of the contents of malonic dialdehyde and lipid hydroperoxides and an increase in the activity of superoxide dismutase and the content of recovered glutathione. Amtizole showed the most pronounced antihypoxic activity and eliminated all negative shifts caused by moderate and heavy hypoxia in the organs studied. Succinic acid did not potentiate the antihypoxic and antioxidant properties of amtizole. Gutimine inhibited the activation of lipid peroxidation and prevented the accumulation of malonic dialdehyde and lipid hydroperoxides and the decrease of recovered glutathione caused by hypoxia in all organs studied. In addition, gutimine inhibited the activity of both superoxide dismutase and catalase. Gutimine succinate exhibited enhanced inhibitory action (as compared to that of gutimine) on lipid peroxidation and removed the inhibition of superoxide dismutase activity in all organs studied. Thus, the present study revealed a parallelism in the antihypoxic and antioxidant effects of aminothiol and triazinoindole derivatives.
Lukk
M V
MV
Zarubina
I V
IV
Shabanov
P D
PD
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D000975:Antioxidants; D007211:Indoles; D008054:Lipid Peroxides; D013438:Sulfhydryl Compounds; D008315:Malondialdehyde