In Vivo and In Vitro Analysis of Toxicity of a Prospective Magnetic Resonance Contrast Agent Based on Arabinogalactan and Gadolinium Nanocomposite.

We studied the cytotoxic effect of gadolinium nanocomposite on cultured mouse fibroblasts 3T3-SV40 and histological changes in the liver tissue of albino rats after its administration. For in vitro experiment, gadolinium nanocomposite on the natural matrix of arabinogalactan (nGd-AG) was dissolved in DMEM nutrient medium to concentrations of 0.005, 0.02, 0.5, 2, and 5 mM. In in vivo experiment, a nGd-AG solution was orally administered to rats through a tube in a dose of 500 µg Gd/kg in 1 ml of 0.9% NaCl for 10 days. The pattern and degree of influence of the gadolinium nanocomposite on the studied cell culture depended on the concentration and duration of exposure. IC50 of nGd-AG determined after cell incubation for 24, 48, and 72 h were 616 µg/kg (3.9 mM), 302 µg/kg (1.9 mM), and 222 µg/kg (1.4 mM), respectively. Histological changes in the liver of white rats induced by exposure to nanocomposite attested to the development of a compensatory reaction of the organ.

Reproductive Function of Male Rats and Motor Activity of Their Offspring in Fire Emissions Modeling.

We studied the reproductive function of albino male rats after long-term exposure to wildfire smoke and the species-specific behavior of their sexually mature offspring. After the end of exposure, the mean number of spermatogonia and the relative number of Leydig cells in rat testes decreased and the index of spermatogenesis decreased. The offspring of exposed males mated with intact females demonstrated impaired cognitive abilities and disturbances of species-specific behavior. The severity of these changes depended on time interval between the end of the inhalation exposure and mating.

Evaluation of Genotoxicity of Perchlozone, Antituberculous Drug.

Experimental studies of Perchlozone, an antituberculous drug with manifest inhibitory activity towards Mycobacterium tuberculosis and Mycobacterium bovis, were carried out. Genotoxicity of Perchlozone was evaluated by the DNA comet method on liver and lung tissues and blood cells after 14-day inhalation exposure of rats. The level of DNA aberrations in response to inhalations of the drug in a concentration of 102.6±13.7 mg/m3 increased in lung tissue but not in the blood cells or liver. These results indicated genotoxic activity of antituberculous drug Perchlozone.

Contribution of Fetal Programming in the Formation of Cognitive Impairments Induced by Lead Poisoning in White Rats.

The contribution of prenatal hypoxic damage to the CNS to the formation of high sensitivity of the body to lead acetate was studied. Prenatal fetal hypoxia was modeled by the administration of sodium nitrite in doses of 5, 25, and 50 mg/kg to pregnant female rats. Cognitive capacities of mature offspring were evaluated in the radial maze test and Morris water maze test. After attaining learning criterion in the radial maze, lead acetate in a dose of 80 mg/kg was added to the drinking water of all animals over 2 weeks. Testing was performed during the exposure to the agent until disruption of the conditioned behavior. It was found that severe prenatal hypoxia (induced by the administration of 50 mg/kg sodium nitrite) impaired spatial memory, increased latency of funding the platform in Morris water maze test, and serves as a factor contributing to earlier manifestations of the neurotoxic effects of lead acetate.

Experimental lead intoxication symptoms with hyperglycemia state.

In lead intoxication model, with hyperglycenia state, atherogenicity coefficient reached 1,45 (1,35-1,85), if compared to 1,30 (0,85-1,40) in white rats exposed to lead. Heart rate reached 421,00 (411,00-468,00) per minute vs, 385,50 (359,00-399,50) per minute in animals died with lead intoxication, shorter median interval between QRS-complexes up to 143,00 (128,00-146,00) ms vs, 160,00 (150,50-169,00) ms was seen in animals exposed to lead.

[The study of neurotoxicity of toluene in conditions of experimental modeling of prenatal hypoxic damage of the brain].

There was executed the study of the impact of toluene on indices of behavior, cognitive capabilities and bioelectric activity of the brain in white rats with normal course of the period of antenatal development and against background ofprenatal hemic hypoxia Prenatal hypoxia was modeled in pregnant female rats by subcutaneous injection of sodium nitrite in a dose of 50 mg/kg at from the 10 to the 19 day of gestation. At the age of 3 months the males from the obtained offspring were exposed to inhalation exposure of toluene (150 ppm, 4 weeks). After exposure to toluene in animals there was evaluated the pattern of individual behavior, indices of cognitive capabilities and also bioelectric activity of the brain. There were revealed such common consistencies of transformations in the behavior of exposed to toluene animals with normal and impaired embryogenesis as disturbed motor activity, reduction of exploratory behavior and cognitive functions, impaired bioelectric potentials of the brain. Features of changes in behavior and EEG indices in toluene-exposed rats with prenatal hypoxia are characterized by inhibition of motor activity, increased anxiety and latency of main peaks of auditory and visual evoked potentials. Prenatal hypoxic damage of the central nervous system was shown to be an aggravating factor in toluene intoxication in rats.

[Neurotoxic effect of toluene on background of prenatal hypoxic brain damage to white rats].

Comparative study covered influence of toluene on behavioral parameters, cognitive abilities and brain bioelectric activity in white rats with normal embryonic development or with prenatal hypoxia. Prenatal hypoxia was simulated by subcutaneous injection of 50 mg/kg sodium nitrite into female white rats on day 13-14 of gestation. The offspring at the age of 2, 5-3 months was exposed to toluene (concentration of 560 mg/m3, 4 hours per day, 5 days per week, over 4 weeks). After the exposure, the animals were estimated for individual and intraspecific behaviour in "open fields and "resident-intruder" tests, for cognitive abilities in "radial maze" training, EEG with visual and auditory evoked potentials. Acute hypoxia at early stages of organogenesis appeared to be burdening factor and to influence consequences of toluene intoxication.