O.A. Safonova, T.N. Popova, Yu.V. Vershkova

Phenilethilbiguanide (PEB) and 2,4-dimetoksiphenilbiguanide (2,4-DMPB) influence on activities of antioxidant enzymes - superoxide dismutase (SOD) and catalase, in rats tissues under brain ischemia/ reperfusion (BIR) was investigated. PEB and 2,4-DMPB were chosen among guanidine derivatives, owning the broad spectrum of biologic action, with the help of computer program for bioactivity prognostication PASS. BIR at white rats males was induced by 30-minutes occlusion of the general carotids and the subsequent occlusors removal. PEB and 2,4-DMPB were introduced to animals with BIR intraperitoneally in 25 mg/kg of weight dose twice a day within 3 days. Definition of piruvate and lactate concentration, SOD and catalase activities were spent spectrophotometrically. In BIR conditions lactate contents increase in 3.3 times on the background of piruvate contents reduction in 2.4 times compared with the control meanings were detected in rats brain. Lactate/piruvate ratio, which is the indicator of the anaerobic carbohydrates transformation intensity, grew in 8 times that testified about the brain oxygenation disorder. Under PEB and 2,4-DMPB introduction to animals with the pathology the piruvate level increase in 1.9 and 2.0 times and the lactate level reduction in 1.8 and 1.9 times as to comparison with the meanings under BIR were revealed. Lactate/piruvate ratio decreased whereat in 3.5 and 3.8 times. It was shown, that in BIR conditions SOD and catalase specific activities increase in 3.4 and 2.5 times in the brain tissue and in 2.2 and 1.9 times in the blood serum of experimental animals compared with the control took place. It was evident, that antioxidant enzymes activities changes had adaptive and compensations disposition as answer to the excessive reactive oxygen species production under the pathology. In group of animals with the ischemic brain injury to which PEB and 2,4-DMPB were introduced, the reduction of SOD activity in 1.9 and 2.5 times in the brain tissue, in 1.4 and 1.6 times in the blood serum relatively BIR was detected. Whereat catalase activity decreased in 1.6 and 1.9 times in the brain, in 1.2 and 1.3 times in the blood serum compared with the pathology. Appearingly, SOD and catalase activities decrease under the biguanides introduction on the background of BIR development was a consequence of these substances display of cerebral protector and antioxidant properties that contributed to free-radical oxidation development inhibition under the pathology and thereby to the reduction of charge on organism main antioxidant chains.