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Experiments with mice showed that heteroaromatic antioxidant IBKhF-11 (intraperitoneally 1 mg/kg) alters the main individual behavior characteristics in the open field test, lessens stress from running on treadmill, reduces oxygen consumption by 33-37% over 3 hours and decreases rectal temperature by 2.4 degrees C at the most. In fact, IBKhF-11 stimulates the anaerobic pathway of energy production during physical work by increasing glucose level etc., and corrects shifts in such biochemical parameters of blood serum as total bilirubin, uric acid and triglycerides and enzyme activities. The low-toxicity compound (intraperitoneal injection of no more than 1500 mg/kg of LD50 on the average) has every potential to appear on the market in the form of performance enhancing drugs.

Toxicity of fullerene C60 in male Wistar rats under conditions of a daily intragastric administration at doses of 0.1; 1 and 10 mg/kg body weight for 92 days was studied. Integral, biochemical, physiological, hematological, immunological indicators were determined that characterized the body condition of animals together with fullerene C60 biodistribution in organs and tissues of rats. Majority of the results didn't show any influence of fullerene C60 on animals treated with it in the whole range of doses studied. On the other hand, some of the data not related to the action of the components used in carrier solution, demonstrated dose-dependent variation: found increased activity on 21-35% in the CYP2B1 at doses of 1 mg/kg and 10 mg/kg body weight, and reduced concentration of uric acid and increasing concentrations of urea at 10 mg/kg body weight. Nevertheless, these changes were within the physiological range of variability. However, it is worth noting an important significant (p = 0.02) increase of the absorption for antigenic proteins in the digestive tract in animals treated with fullerene C60 at a dose of 10 mg/kg, suggesting a marked effect on the intestinal wall.

The antioxidant activity, mutagenicity, and genotoxicity of bis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propyl)sulfide (thiophane) were studied using bacterial tests. The results of both an Ames test and SOS chromotest, as well as those studying the survival of E. coli cells deficient in enzymes responsible for the repair of DNA oxidative damage, testify to the fact that thiophane is not mutagenic and genotoxic, and it protects Salmonella typhimurium cells better than the well-known antioxidant trolox.

Selenium is essential trace element, sulphur analogue with high chemical activity, component of some selenoproteins and enzymes: glutathione peroxidase and other peroxidases, blood and tissue proteins. As to their biological action mechanism selenium and its compounds are antioxidants. Selenium is active immunomodulator, much more potent anti-oxidant than vitamins E, C and A, beta-carotene, but much more toxic. It takes part in thyroxine conversion to triiodethyronine in thyroid hormone biosynthesis. As sperm antioxidant selenium protected its motility and fertility. Selenium is a serious factor of biological and antioxidant protection of vascular endothelium, of low-density lipoproteins, protection of DNA, chromosomes. As food component selenium is an exceptional agent of protection from atherosclerosis, coronary ischemic disease and cancer. Some hydrobionts, liver, kidney, meal, corn and garlic, onion, cabbage, broccoli are dietary products with high content of selenium.

The results of pharmacological tests showed that betulin bishemiphthalate possesses hepatoprotector, antioxidant, and immunotropic properties. Administered in combination with hydroxymethyluracil, that betulin bishemiphthalate prevented the loss of experimental animals upon irradiation.

Mexidol, emoxypine, and dimephosphon decrease the acute toxicity of nibentan in mice. In the experiments on cats, these drugs reduced the negative dromotropic action of nibentan and prevented an increase in the effective refractory period of the atrioventricular node and ventricles, in the QT interval length, and in the ventricular excitation threshold.

Pyridyl-3-glyoxylic acid reduced the blood cholesterol and triglycerides, normalized the lipoprotein spectrum, markedly decreased the intensity of lipid peroxidation, and increased the superoxide dismutase enzyme activity in the experimental rabbits with cholesterol atherosclerosis model. The efficacy of the compound exceeded that of nicotinic acid used as the reference compound.

Ammonia succinate potentiates the main pharmacological properties and reduces the toxic effects (ulcerogenic action and general toxicity) of acetylsalicylic acid. The new preparation astam, representing a combination of acetylsalicylic acid with ammonia succinate in a 2:1 ratio, is proposed. Astam exhibits antiexudative, capillary-reinforcing, antiproliferative, pain-relieving, antipyretic, antiaggregant, and antioxidant properties. In addition, the drug inhibits the development of structural-metabolic disorders in the case of chronic immune inflammation of joints and various internal organs.

The influence of lacidipine (0.1-10 mg/kg, intragastric) on the clastogenic effect of dioxidine (100 and 200 mg/kg, i.p.) under conditions of their single and repeated (five-fold, 24-h interval) administration was studied by the chromosome aberration assay in the metaphase bone marrow cells of BALB/c and C57BL/6 male mice. It was found that single (5 or 10 mg/kg) and repeated (10 mg/kg) introduction of lacidipine enhances the clastogenic effect of dioxidine in both genotypes. At the same time, a single treatment of C57BL/6 mice with 0.1 and 1 mg/kg of lacidipine sometimes significantly reduced the clastogenic effect of dioxidine (200 mg/kg). Thus, lacidipine exhibits a comutagen effect in vivo when administered at large doses (5 and 10 mg/kg) but not at small doses, where the drug sometimes acted as antimutagen in C57BL/6 mice.

Subchronic tests on rats showed that a new phenolic antioxidant bis[3,(3, 5-di-tert-butyl-4-hydroxyphenyl)propyl] sulfide (SO-3) exhibits low toxicity upon peroral administration. Neither significant variations in the hematological and integral indices, nor pathological shifts in the activity of serum enzymes or pathomorphological changes in the internal organs were observed. Simultaneous administration of a sunflower oil with SO-3 led to a significant decrease in the blood cholesterol level, produced a hepatoprotector effect, and exhibited a protective action with respect to the mucous membranes of the gastrointestinal tract. Animals receiving large doses of SO-3 showed no signs of a prelipid stage of the arteriosclerosis typically observed in the control group.

The anti-ischemic and toxic effects of different doses of the antioxidant ionol (butyl hydroxytoluene, BHT) introduced into the Krebs-Henseleit medium composed of monolayer liposomes of egg phospholipids before or 30 minutes after total ischemia of the heart were studied on a model of perfusion of isolated Wistar rat heart by the method of Langendorff-Fallen. It has been demonstrated that ionol, after its addition to the perfusate in the preischemic period, exerts an anti-ischemic effect in concentrations of 10(-6), 3 x 10(-6) and 10(-5) M; in the postischemic period, in concentrations of 3 x 10(-6) and 10(-5); the protective effect of ionol in the postischemic period is less pronounced. In higher doses (3 x 10(-5) and 10(-4) M) ionol produces a toxic action which is more remarkable and is less reversible in respect to the ischemized than to the nonischemized heart, and is realized rather through the dysfunction of heart muscle relaxation. The conclusion is drawn that there is a possibility of using ionol in doses of 10(-6) to 10(-5) M as a constituent of liposomes for addition to perfusion, conservant and cardioplegic solutions as an anti-ischemic remedy.

After the long-term administration of doxilane-diolane, cresacin, antioxidant S-1 and fluorine varnish to mongrel albino rats and mice no difference in the level of spontaneous tumours both in the control and experimental groups of animals was observed. It is concluded that these drugs possess no carcinogenic activity.

During experiments on rats it was established that some methoxy- and nitro-derivatives of acridinyl-9-thioacetic acids possess the hepatoprotective properties contributing to a decrease of the liver tissue cell destruction under the action of CCl4 and lipid peroxidation in the liver.

The changes in toxic, mutagenic and carcinogenic activities of benzo(a)pyrene (BP) in combination with two new phenolic antioxidants, phenosan-acid and -ester, were studied. Although both phenols investigated were characterized by marked toxic and mutagenic activity, their combination with BP appeared to protect mammalian cells against the action of the carcinogenic substance. A distinct correlation between inhibition of the mutagenic and toxic activities of BP and the dose of antioxidants was observed. The effect of phenosans on skin carcinogenesis induced by BP depended to a larger degree on the conditions of application of test substances. When combined applications of BP and antioxidants to the skin of mice were used, phenosans suppressed carcinogenesis, thus prolonging the latent period of tumor induction. When two-stage scheme of carcinogenesis was applied, a tendency for development predominantly benign skin tumors under the influence of antioxidants was noted. The use of the new phenolic antioxidants--phenosan-acid and -ester--seems to offer advantage in reducing mutagenicity and carcinogenicity of polycyclic aromatic hydrocarbons.

Toxicity of the antioxidant dodecyl gallate was studied in 150-day experiments on male white rats. The antioxidant was administered intragastrically in doses of 250, 50 and 10 mg/kg bw. The general status and behavior of the animals, the survival rate, weight gain, peripheral blood, the amount of urea, total serum protein, soluble proteins of the liver and kidneys, and activity of enzymes (AST, ALT, LDH, SDH, glucose-6-phosphate dehydrogenase, alkaline and acid phosphatase of the serum, liver and kidneys, the weight of the internal organs) were studied over time, followed by morbid anatomy studies. Quantitative determination of serum lipids (total fats, total cholesterol, esterified cholesterol, free cholesterol, triglycerides, free fatty acids, triglycerides plus free fatty acids, and phospholipids) was made on the 150th day after the onset of experiments. When administered in a dose of 250 mg/kg, dodecyl gallate produced death of the animals and an increase in the content of triglycerides plus free fatty acids, a decrease in the weight of the spleen and morphological alterations in the liver, kidneys and spleen. The dose 50 mg/kg was also toxic. It brought about changes in the activity of serum and liver AST, an increase in the content of TF, TG, FFA, TG plus FFA and phospholipids, a reduction in the weight of the spleen and pathological changes in the liver, kidneys and spleen. The dose 10 mg/kg is regarded as liminal.