Correction of consequences of postischemic reperfusion brain damages with cytoflavin

Abstract

Cytoflavin normalized energy metabolism, decreased the intensity of lipid peroxidation, and restored activity of the antioxidant system in rat brain during postischemic reperfusion. Cerebroprotective effect of cytoflavin was similar to that of piracetam. Key Words: cytoflavin; piracetam; ischemia; postischemic reperfusionHypoxia plays the major role in the pathogenesis of acute ischemic damages to cerebral blood flow. Hypoxia triggers the cascade of metabolic transformations modulating the intensity of energy metabolism and lipid peroxidation (LPO) [1,8]. Therefore, the therapy of acute cerebral ischemia should include not only correction of cerebral blood flow with vasoactive, fibrinolytic, and antiaggregant agents, but also normalization of energy metabolism and stabilization of cell membranes and subcellular structures in nerve cells.Here we studied effects of cytoflavin on brain metabolism during postischemic reperfusion damage. Cytoflavin (Polysan) is a complex preparation containing succinic acid, purine nucleoside (riboxine), nicotinamide, riboflavin mononucleotide, and N-methyl-D-glucamine (solubilizer). MATERIALS AND METHODSExperiments were performed on 100 male outbred albino rats weighing 180-200 g (Rappolovo nursery). Ischemic brain damage was induced by 90-min occlusion of the common carotid arteries followed by repeffusion. The effect of cytoflavin (1.5 ml/kg) on postischemic brain damage was examined 24 and 72 h after reperfusion. The effects of cytoflavin were comDepartment of Neuropharmacology, Institute of Experimental Medicine, Russian Academy of Medical Sciences; Polisan Research-andProduction Pharmaceutical Company, St. Petersburg pared with those of piracetam (100 mg/kg). Control animals received an equivalent volume of physiological saline. The preparations were injected intraperitoneally 2 times a day. Control group comprised shamoperated rats.Energy metabolism in brain tissue was evaluated by the content of lactate and pyruvate [15] and lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) activities [5,6]. The intensity of LPO was estimated by the concentrations of malonic dialdehyde (MDA) and conjugated dienes (CD) of unsaturated fatty acids [12,13]. The state of the antioxidant system was analyzed by superoxide dismutase (SOD) activity and content of reduced glutathione (GSH) [3,11].-The results were analyzed by Student's t test. RESULTSThe content of lactate and LDH activity in rat brain after common carotid artery occlusion increased by 194 and 107%, and pyruvate concentration and SDH activity decreased by 54 and 51%, respectively, compared to the control (Table 1). The lactate/pyruvate ratio reflecting the intensity of aerobic or glycolytic carbohydrate metabolism increased from 8.6 to 55.4. These data indicated inhibition of aerobic and stimulation of glycolytic (emergency) mechanisms of energy formation. The intensity of LPO increased, and the antioxidant system was suppressed in the ischemic brain. The 0007-4888/00/0002-128525.00 9Kluwer Academic/Plenum Publishers Metabol...

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Effects of 2,4-Dimethoxyphenyl Biguanide on Glutathione System Activity in Rat Tissues in Brain Ischemia–Reperfusion

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Comparative study of cardioprotective effects of uridine-5′-monophosphate and uridine-5′-triphosphate during the early periods of acute myocardial ischemia

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