Neuroprotective Effects of Peptides during Ischemic Preconditioning.

Experiments on rats showed that neurospecific protein preparations reduce the severity of neurological deficit, restore the structure of individual behavior of the animals with different hypoxia tolerance, and exert antioxidant action during chronic ischemic damage to the brain unfolding during the early and late phases of ischemic preconditioning.

Antioxidant Effect of Polyoxidonium and Metaprot during Bronchopulmonary Inflammation in Rats.

The antioxidant effects of individual or combined application of polyoxidonium and metaprot were examined in rats with acute bronchopulmonary inflammation. By degree of antioxidant potency, polyoxidonium was inferior to metaprot, but their combined application produced more potent antioxidant effect. Polyoxidonium and metaprot in low concentrations increased and in high concentrations suppressed spontaneous biochemiluminescence in the model system of alveolar macrophages.

[Analysis of tropalgin effects in an inflammation pain model in rats with different pain threshold].

Individual pain sensitivity of male Wistar rats was determined in a tail-flick model after action of focused thermal ray (flick) on tail. Rats with latency less than 5 sec were qualified as high sensitive (HS) to pain, more than 10 sec as low sensitive (LS) to pain. Effects of a new nonopioid analgetic tropalgin 2 mg/kg (ED50) i.p. was studied in both groups of rats. Tropalgin was effective as an analgetic in aseptic inflammation model (formaldehyde test). The analgetic effects of tropalgin were same as after administration of methamizol sodium (50 mg/kg) or diclofenac sodium (7 mg/kg). Tropalgin did not change individual pain sensitivity in both HS and LS rats without inflammation. In HS to pain rats, the common time of pain behavioral reactions was decreased by 53% in an acute phase of pain and by 58% in a tonic phase of pain in inflammation pain model. In LS to pain rats, the time of leaking of inflamed paw was decreased by 42% in the first phase and by 66% in the second phase. We suggest that analgetic effect of tropalgin is connected with adenosine release in purinergic neurons that has been demonstrated earlier for drugs of tropin structure.

[ANALGESIC EFFECT OF TROPALGIN ON THERMAL PAIN IN RATS WITH DIFFERENT PAIN THRESHOLDS].

Experiments on rats divided into two groups (with high and low pain sensitivity) were used to assess the effect of tropalgin, a new derivative of tropine, in thermal pain tests (tail-flick and hot plate). Tropalgin was found to possess an analgesic effect comparable to that of reference sodium metamizole. ED50 of tropalgin was 2 mg/kg for intraperitoneal administration. The duration of the analgesic effect of tropalgin in rats low pain sensitivity was longer than in animals highly sensitive to pain. It is suggested that the analgesic effect of tropalgin can be related to the adenosine liberating action of this drug.

[Protective effects of metaprot and ethomerzol in carbophos intoxications].

The mechanisms of protective action of thiobenzimidazole derivatives metaprot and ethomerzol (25 and 50 mg/kg) have been studied on a model of carbophos intoxication (256.0 +/- 8.7 mg/kg) in rats. Both compounds recovered the resistance to physical loads in forced swimming test, normalized the activity of aspartate and alanine transaminases, and reduced bilirubin, creatinine, and urea nitrogen levels in the blood serum. The intoxication was accompanied with increasing concentration of malonic dialdehyde and decreasing level of recovered glutation in the blood, as well as with the signs of endogenic intoxication. Metaprot and ethomerzol diminished disorders of both the lipid peroxidation and endogenic intoxication processes. Thus, the antihypoxic, antioxidant, actoprotective, energotropic, and reparative effects of metaprot and ethomerzol have been proved. Ethomerzol was more effective than metaprot in these tests.

Antihypoxic and antioxidant effects of exogenous succinic acid and aminothiol succinate-containing antihypoxants.

Pronounced antihypoxic and antioxidant effects of preventive injection of succinic acid, aminothiol antihypoxants gutimine and amtizol, and succinate-containing aminothiol antihypoxants gutimine succinate and amtizol succinate to Wistar rats with acute hypoxic hypoxia have been demonstrated. Exogenous succinic acid was inferior to aminothiol compounds by antihypoxic effect, but superior to them by its effect on the level of LPO products. Succinate in the aminothiol molecule modulated the intensity of their antihypoxic and antioxidant effects. It did not modulate the antihypoxic activity of amtizol, but reduced the antihypoxic effect of gutimine, presumably because of the physicochemical characteristics of aminothiols. Comparison of the intensities of antihypoxic and antioxidant effects of the studied drugs showed no direct relationship between these effects.

[Significance of pain sensitivity for the resistance to immobilization stress].

The effects of immobilization stress (immobilization on back within 4 h) on the functional indexes of Wistar male rats differing with pain sensitivity in the tail-flick test were studied. The acute immobilization stress in rats with high pain sensitivity compared with low pain sensitivity animals produced the most changes of the main functional systems. The high pain sensitivity rats demonstrated more significant hypotension, bradicardia, temperature shift, decrease of breath frequency and oxygen consumption, acid-alkaline equilibrium disorders with lactate acidosis signs. Therefore, the rats with low pain sensitivity possess the high resistance to acute stress exposure in comparison with high pain sensitivity animals. This confirms the important significance of individual pain sensitivity for the formation of stress resistance.

[Hepatoprotective properties of cytochrome C in traumatic toxicosis].

Experiments on rats showed that traumatic toxicosis (crush syndrome) was accompanied by disorders of both excretion and detoxication functions of the liver and a decrease in the energy potential of the liver. Systemic administration of cytochrome C (10 mg/kg) immediately after trauma and decompression increased the level of endogenous cytochrome C, recovered the pool of adenine nucleotides, normalized bromsulfaleine excretion from the blood, and decreased the content of toxic metabolites in the blood. The obtained experimental data show that cytochrome C possesses high hepatoprotective properties with respect to the development of traumatic toxicosis.

[Cortexin and cortagen as correcting agents in functional and metabolic disorders in the brain in chronic ischemia].

The polypeptide drug cortexin and the synthetic peptide drug cortagen accelerate the recovery of disturbed individual behavior of ischemic rats with different resistance to hypoxia (high and low resistant rats). In addition, both drugs prevented an excessive activation of lipid peroxidation and a decrease in the antioxidant activity in the brain tissues. The obtained results suggest that cortexin and cortagen can be used for increasing the efficacy of neuroprotective therapy in cases of chronic brain ischemia.

[The significance of individual sensitivity to hypoxia for the duration of severe compression trauma].

In the experiments on rats was shown that individual differences in sensitivity to hypoxia were significant for subsequences of long-term immobilization stress and severe compression trauma. In these conditions, low resistant rats were more sensitive to hypoxia compared with high resistant animals. The low resistant rats had got more significant changes of the main functional systems and acid-alkaline buffer state.

[Efficacy of cytoflavine in treating traumatic toxicosis].

Experiments on rats showed that traumatic toxicosis (crush syndrome) was accompanied with hypotension, bradycardia, reduction in temperature, breath frequency, and oxygen intake, and violation of acid-base buffer state with elevation of lactate acidosis in the blood serum that is typical of shock performance. Substrate combined antihypoxant cytoflavine (1.5 ml/kg) administered systemically to rats immediately after decompression, increased percentage of survived rats and recovered the main indexes of functional systems and acid-base buffer state 12 h after trauma, which provided general protection of rats against traumatic toxicosis.

Comparative efficiency of succinate-containing antihypoxants in traumatic toxicosis.

Experiments on Wistar rats showed the development of endotoxicosis 12 h after severe compression injury. Endotoxicosis manifested in disorders in bromosulfaleine excretion from the blood, increase of blood urea, uric acid, creatinine, and potassium levels and aminotransferase activities. Injection of succinate-containing antihypoxants (reamberine, cytoflavin, metaprot plus, succinamic acid 2-amino-4-acetylthiasolo[5,4-b]indole) directly after decompression promoted recovery of liver function, prevented the development of hyperfermentemia and renal failure as a result of reduced blood levels of potassium and non-protein nitrogen. The protective effect of the drugs in traumatic toxicosisdecreased in the following order: metaprot plus>cytoflavin>2-amino-4-acetylthiasolo[5,4-b]indole succinaminic acid>reamberine.

[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.

Noopept reduces the postischemic functional and metabolic disorders in the brain of rats with different sensitivity to hypoxia.

Chronic cerebral ischemia was induced by ligation of both common carotid arteries in Wistar rats, divided by sensitivity to hypoxia into highly sensitive and low-sensitive. Noopept (peptide preparation), injected (0.5 mg/kg) during 7 days after occlusion of the carotid arteries, reduced the neurological disorders in rats with high and low sensitivity to hypoxia and improved their survival during the postischemic period. Noopept normalized behavior disordered by cerebral ischemia (according to the open field and elevated plus maze tests), prevented accumulation of LPO products and inhibition of antioxidant systems in the brain of rats with high and low sensitivity to hypoxia. Hence, noopept exhibited a neuroprotective effect in cerebral ischemia.

[Effect of cytoflavine on bioenergetic processes in the liver after severe limb compression trauma].

The experiments on rats showed that severe compression trauma of limb muscles leads to a decrease in the energetic potential of the liver. Cytoflavine injected in rats with model traumas increased the content of ATP and cAMP and decreased the level of ADP and AMP, thus recovering the energetic potential of adenine nucleotides in the liver.

Functional activity of the liver during severe compression injury.

Severe compression injury in rats was accompanied by metabolic acidosis, cytolytic syndrome, disturbances in liver excretory function and detoxification, and change in biotransformation processes.

Metabolic effects of Trekrezan during adaptation of rats to intermittent hypoxic hypoxia.

The animals were adapted to intermittent hypoxic hypoxia in a flow pressure chamber for 3 days. Each one-day training session consisted of 4 elevations to an altitude of 6000 m for 20 min (15 m/sec, 20-min intervals between assents). Trekrezan (25 mg/kg intraperitoneally) was injected immediately after the end of daily training over 3 days. We showed that trekrezan increased the degree of adaptive metabolic changes in the brain, heart, and liver of rats during adaptation to hypoxic hypoxia.

[Morphometry of hepatocyte mitochondrial apparatus in normal and cirrhotic rat liver].

Morphometric electron microscopy study of the hepatocyte mitochondrial apparatus and morphofunctional analysis of the degree of pathological alterations were carried out on the liver of rats with CCL4-cirrhosis (experimental group). Chronic poisoning of rats with CCL4 for 6 months led to a 4.2-fold increase in proportion of connective tissue and to a decrease in the number of hepatocytes in the liver by 21.8 %. Dry mass and ploidy of hepatocytes in the cirrhotis liver rose as compared with norm by 20.6 and 9.3%, respectively. Activities of alanine and aspartate aminotransferases in blood of rats of experimental group exceeded normal ones 2.0 and 1.4 times, respectively. Concentration of total bilirubin in blood of the cirrhotic animals increased 1.7 times, while concentration of total protein decreased by 22%. Concentration of diene conjugates in the liver of rats of experimental group increased 2.1 times as compared with normal one, while the level of malonic dialdehyde - by 34%. Activities of superoxide dismutase and catalase in the cirrhotic liver were lower than in the normal liver were lower than in the normal liver by 16 and 23 %, respectively. Morphometry of the hepatocyte mitochondrial apparatus has shown that in spite of an increase in the voluminous density of mitochondria in hepatocytes of the cirrhotic liver (by 28 %), concentration of internal mitochondrial membranes in the cells was reduced almost 1.5 times, while the total length of internal membrane in a single mitochondrion was reduced about twice as compared with norm. Thus, despite compensation of the partial loss of hepatocytes because of their polyploidization and hypertrophy, the specific synthetic activity of cells in the case of cirrhosis is decreased due to deterioration of the antioxidant system and electron transport chain of the mitochondrial apparatus.

[Functional and metabolic changes of healthy volunteers after cold exposure and administration of meteoadaptogen trekrezan].

The effect of cold exposure (-10 degrees C, air speed--2.5 m/sec, 40 minutes) on physical activity, cognitive processes and metabolic status of 75 volunteers, healthy men of 20-24, was studied in termobarocomplex Tabaj (Japan). Cold exposure reduced physical and cognitive activity, the activity of kreatine phosphokinase, superoxide dismutase, the levels of redox glutation and pyruvate. Preliminary administration of adaptogenic drug trekrezan 0.2 g prior to cold exposure normalized the indexes studied of physical activity and metabolic status. It is suggested that trekrezan can be used as a meteoadaptogenic drug for rapid and effective adaptation to cold exposure of environment.

[Comparative study of the energy-stabilizing and immunotropic properties of trekrezan and polyoxidon on a bronchopulmonary inflammation model in rats].

The energy-stabilizing and immunotropic action of immunomodulants trekrezan (25 mg/kg) and polyoxidon (0.75 mg/kg) was compared in rats with a model bronchopulmonary inflammation induced by the introduction of turpentine into trachea. Both drugs exhibited an energy-stabilizing effect, which was manifested by a decrease in the levels of lactate and the ATP-ADP and AMP hydrolysis products and by an increase in the level of pyruvate and ATP in blood lymphocytes and lung tissues. The energy-stabilizing action of polyoxidon was more pronounced in the lung tissue. The action of this drug was generally the same, but less pronounced than the effect of trekrezan. The parallel experiments showed that trekrezan and polyoxidon normalized the immune status of lymphocytes in rats with the model acute bronchopulmonary inflammation.