Prenatal effects of peat combustion products and afobazole correction thereof in the rat progeny.

Female outbred albino rats were daily subjected to forced inhalations of peat smoke (4 cores packed with a mixture of peat (70%) and wood pulp (30%); 0.46 g, pH ≥ 5.5) per se and in combination with oral afobazole (anxiolytic) on days 1-20 of pregnancy. Exposure to peat smoke inhibited body weight gain in pregnant rats, caused an increase of postimplantation deaths, reduction of fetal weights, and an increase in the number of hematomas and hemorrhages in fetuses. Afobazole in doses of 1 and 10 mg/kg reduced significantly the untoward effects of peat smoke on fetal development.

[Preclinical safety investigation of GB-115 dipeptide].

Preclinical safety investigations of newly synthesized dipeptide compound GB-115 (amide N-phenylhexanoyl-glycyl-L-tryptophan), an antagonist of cholecystokinin receptors, were performed. No animals were lost after GB-115 acute oral administration at a maximum dose of 6000 mg/kg in mice and at 3500 mg/kg in rats. GB-115 administered per os during 6 months in rabbits and rats (both males and females) at the doses of 0.1 and 10 mg/kg induced no irreversible pathological changes in organs and systems studied. The tested dipeptide exhibited no allergenic, immunotoxic and mutagenic activity, and did not affect generative function and the antenatal and postnatal development of progeny. GB-115 at a dose of 10 mg/kg produced suppression of the inflammatory reaction to concanavalin A.

Evaluation of genotoxicity and reproductive toxicity of silicon nanocrystals.

Silicon crystal 2-5 nm nanoparticles in the form of 1-5-µ granules in water suspension were injected intraperitoneally in a single dose to male F(1)(CBA×C57Bl/6) mice or to outbred albino rats on days 1, 7, and 14 of gestation. Silicon crystal nanoparticles in doses of 5, 25, and 50 mg/kg exhibited no cytogenetic activity in mouse bone marrow cells after 24-h exposure and in doses of 5 and 25 mg/kg after 7 and 14-day exposure. A 24-h exposure to silicon nanoparticles in a dose of 5 mg/kg significantly increased DNA damage (detected by DNA comet assay) in bone marrow cells. In a dose of 50 mg/kg they considerably increased DNA damage in bone marrow and brain cells after exposure of the same duration. Silicon nanoparticles in doses of 5 and 50 mg/kg caused no genotoxic effects in the same cells after 3-h and in a dose of 5 mg/kg after 7-day exposure. Silicon crystal nanoparticles in a dose of 50 mg/kg caused death of 60-80% mice after exposure <24 h. Injected in a dose of 50 mg/kg on days 1, 7, and 14 of gestation, silicon crystal nanoparticles reduced body weight gain in pregnant rats and newborn rats at different stages of the experiment, but had no effect on other parameters of physical development of rat progeny and caused no teratogenic effects.

[The effect of hemantane on the generative function and gonad morphology in rats]. / Vliianie Gimantana na generativnuiu funktsiiu i morfologiiu gonad.

Effect of the new potential antiparkinsonian drug hemantane (N-(adamant-2-yl)hexamethyleneimine hydrochloride) on the generative function and gonad morphology was studied in a group of male and female mongrel rats. The generative function was studied after peroral drug administration in a dose of 10 mg/kg (ED50) and 50 mg/kg (5 ED50): males were treated over a 60-day period of spermatogenesis, while females received the drug in the same doses over 15 days (three estrous cycles). The gonad morphology was studied after a 6-month treatment of experimental animals with hemantane in the same doses. It was established that the administration hemantane in indicated doses did not influence the generative function and gonad morphology in male and female rats.

[Effect of himantane on the rat embryo development]. / Vliianie gimantana na émbrional'noe razvitie krys.

Himantane introduced via a gastric tube to pregnant rats in a dose of 10, 30, 50, and 100 mg/kg produced a dose-dependent embryotoxic and teratogenic action. An analysis of the experimental results and published data suggests that the embryotoxicity of himantane can be related to its general toxic action upon the organism of pregnant female rats.

[Preclinical study of noopept toxicity]. / Doklinicheskoe izuchenie toksichnisti noopepta.

Within the framework of a preclinical investigation, the new nootrope drug noopept (N-phenyl-acetyl-L-propyl-glycine ethylate) was tested for chronic toxicity upon peroral administration in a dose of 10 or 100 mg/kg over 6 months in both male and female rabbits. The results of observations showed that noopept administered in this dose range induced no irreversible pathologic changes in the organs and systems studied and exhibited no allergenic, immunotoxic, and mutagen activity. The drug affected neither the generative function nor the antenatal or postnatal progeny development. Noopept produced a dose-dependent suppression of inflammation reaction to concanavalin A and stimulated the cellular and humoral immune response in mice.

[The effect of lithium oxybutyrate on the development of the fetus and progeny in alcoholic intoxication of male rats]. / Vliianie litiia oksibutirata na razvitie ploda i potomstva v usloviiakh alkogol'noi intoksikatsii samtsov krys.

The effect of lithium hydroxybutyrate on the development of the fetus and offsprings was studied on a model of alcohol intoxication of male rats. Under such conditions lithium hydroxybutyrate relieved completely the negative action of alcohol on the reproductive function, according to all parameters. The learning ability of the offsprings and their behavioral disorders in a stress situation caused by alcohol were normalized. Two-week administration of 100 mg/kg lithium hydroxybutyrate had no negative effect on the embryonal and postnatal development of the offsprings.

[The significance of perinatal alcoholization and its withdrawal in the development of late cognitive disorders in rats]. / Zanchenie perinatal'noi alkogolizatsii i ee otmeny v razvitii otdalennykh kognitivnykh narushenii u krys.

To study the effect of perinatal alcoholization and its withdrawal on cognitive functions of rats, 25% ethanol solution was administered intragastrically: (1) over the whole period of the rat pregnancy in a dose of 5 g/kg/day; (2) from the Ist day of pregnancy to the 7th day after genera in a dose of 5 g/kg/day; (3) from the Ist day of pregnancy to the 2nd day after genera in a dose of 5 g/kg/day; and then in daily decreased doses (by 1g/kg) to the 7th day. A less pronounced increase in the rat mass and disturbances in maternal behavior (eating up the descendants) was observed for all alcoholization regimes. Alcoholization inhibited the eye opening, but did not affect the body mass increase and elementary inborn reflexes of descendants during the first three weeks of life, whereas in adult male descendants alcoholization deteriorated the ability to training and memory on the "open field" model and bilateral avoidance response. The cognitive disorders in descendants were more pronounced after abrupt withdrawal of ethanol directly after the birth and were minimal after gradual withdrawal of alcohol.

[The correction with nooglutil and L-pyroglutamyl-D-alanine amide of cognitive disorders in rats due to intrauterine hypoxia]. / Korrekstiia noogliutilom i amidom L-piroglutamil-D-alanina kognitivnykh narushenii u krys, vyzvannykh vnutriutrobnoi gipoksiei.

Novel nootropic compounds, nooglutyl (N-5-hydroxy(nicotinoyl)-L-glutamine acid, 25 mg/kg/day) and L-pyroglutamyl-D-alanine amide (1 mg/kg/day) administered intracutaneously from the 8th to 20th day of life prevent from movement hyperactivity in "open field", disturbances in ability to training and in memory in an alternate test and in tests of passive and active avoidance and normalize behavior of the adult mail rats (subjected to two-hour hypobaric hypoxia in on the 15-day of intrauterine life, vacuum corresponded to the height 8500 m) in-extrapolation avoidance test. Additionally, nooglutyl recovered the normal growth of rats in the first month of their life, prevented from deceleration of investigating behavior of adults animals and disturbances of the mink reflex in them.

[Sodium oxybutyrate normalizes the central nervous system functions in the progeny of rats subjected to hypobaric hypoxia during pregnancy]. / Natriia oksibutirat mormalizuet funktsii tsentral'noi nervnoi sistemy u potomstva krys, podvergshikhsia gipobaricheskoi gipoksii vo vremia beremennosti.

Two-hour hypobaric hypoxia of rats on day 15 of their pregnancy led to a reduction in weight gain of pups within 20 days after birth, disturbed memory in active and passive paradigms, changed adaptive behavior in the extrapolatory water avoidance test, and impaired sleep in adult animals. Postnatal treatment with sodium hydroxybutyrate given in a dose of 50 mg/kg/day on days 8 to 20 of life normalized mnestic functions of the brain, the process of falling asleep, and physical development which had been impaired by intrauterine hypoxia.

[The effect of fenazepam and phenobarbital on the course of pregnancy in rats and on the early postnatal development of their progeny]. / Vliianie fenazepama i fenobarbitala na techenie beremennosti krys i rannee postnatal'noe razvitie ikh potomstva.

Examining the effects of phenazepam and phenobarbital on the course of pregnancy and the development of offsprings has revealed that phenobarbital that has an embryotoxic effect reduced the number of rat offsprings and diminished their weight, but failed to affect the behavioral responses of newborn rats. On the contrary, phenazepam had no embryotoxic effect, but on entering the newborn rats' organism with milk it inhibited some behavioral reactions in the early postnatal period.

[Behavior disorders in rats exposed to intrauterine hypoxia, and their correction by postnatal treatment with piracetam]. / Narusheniia povedeniia krys, podvergshikhsia vnutriutrobnoi gipoksii, i ikh korrektsiia postnatal'nym vozdeistviem piratsetama.

Hypobaric hypoxia of the pregnant rats was followed by the reduction of weight gain of the newborn pups, delayed impairment of memory (passive and active tasks) and changes of extrapolative water escape. Piracetam (200 mg/kg/day) administered at early postnatal period (from 8th to 20th day of life) corrected behavioral disturbances and physical development in rats. Postnatal therapy by nootropics didn't influence in adaptive behavior damaged by prenatal hypoxia.

[The lithium oxybutyrate correction of disorders in higher nervous activity in the progeny of alcoholized male rats]. / Korrektsiia litiia oksibutiratom narushenii vysshei nervnoi deiatel'nosti potomstva alkogolizirovannykh krys-samtsov.

In experiments on rats it was shown that alcohol administered intragastrically in a dose of 8 g/kg for 4 weeks produced long-term disturbances of CNS function in the offspring similar to those observed under clinical conditions. Early postnatal administration of lithium oxybutyrate (from the 8th through the 14th day of life) was found to prevent the development of the disturbances.

[A behavioral and biochemical analysis of the therapeutic effect of sodium oxybutyrate in alcoholic encephalopathy in progeny]. / Povedencheskii i biokhimicheskii analiz terapevticheskogo éffekta natriia oksibutirata pri alkogol'noi éntsefalopatii u potomstva.

The alcoholization of pregnant female rats (5 g/kg) results in a decrease of endogenous ethanol level in their offspring and distant disturbances of the conditioned reflex activities of the young rats deteriorating the formation and preservation of the skill with an emotional positive reinforcement. Sodium gamma-gydroxybutyrate administered in a dose of 50 mg/kg from the 8th to the 20th day of life prevents the above-mentioned disturbances of learning and memory, restores the level of endogenous ethanol, corrects the parameters of lipid and mediator metabolism in the brain and blood changed by prenatal alcoholization.

[L-pyroglutamyl-D-alanine amide normalizes the function of the developing brain damaged by antenatal alcoholization in rats]. / Normalizatsiia amido L-piroglutamil-D-alanina funktsii razvivaiushchegosia mozga, narushennykh antenatal'noi alkogolizatsiei krys.

The effects of the synthetic dipeptide, L-pyroglutamyl-D-alaninamide (LPDA) were studied in the experiments on offspring of alcoholized during the pregnancy (5 g/kg/day) females. This dipeptide, which revealed the nootropic activity in previous experiments, was injected to the pups in dose of 1 mg/kg from 8 to 19 days of life. LPDA was shown to prevent the delayed disturbances of learning in passive avoidance test, of extrapolatory behaviour in escape test, to attenuate the emotional hyperreactivity. LPDA normalized EEG power spectrum, decreased interhemispheric asymmetry. This substance attenuated the disbalance evoked by prenatal alcoholization.

[Sodium oxybutyrate correction of the disorders in higher nervous activity in the progeny of alcoholized animals]. / Korrektsiia natriia oksibutiratom narushenii vysshei nervnoi deiatel'nosti potomstva alkogolizirovannykh zhivotnykh.

Alcoholization of female rats before pregnancy (8 g/kg) or during pregnancy (4 g/kg) leads to disturbances in the development of the offspring higher nervous activity manifested by impaired learning abilities, disordered emotional reactivity, reduced capacity to overcome stress-situation, deficit of GABAergic inhibitory processes in the cerebral cortex. An early postnatal administration of sodium hydroxybutyrate in a dose of 50 mg/kg prevents the development of the above mentioned disturbances of the higher nervous activity and neurophysiological alterations.

[Effect of teturam on the development of the offspring of alcoholized animals]. / Vliianie teturama na razvitie potomstva alkogolizirovannykh zhivotnykh.

During experiments on rats it was found that in alcoholized animals teturam on the whole did not potentiate and in some cases even attenuated the toxic effect of alcohol on the offspring development. The data confirm the idea about necessity of studying toxicity of drugs under the conditions corresponding to their clinical use.

[Effect of alcohol and teturam on the gonads of male rats and their progeny]. / Vliianie alkogolia i teurama na gonady samtsov krys i ikh potomstva.

Experiments on rats were made to study the effect of alcohol and teturam on the function of spermatozoa and spermatogenesis of males and their progeny. The male-mediated damaging action of alcohol on the gonads of the progeny was ascertained. That might be one of the causes of the maldevelopment in subsequent generations of the progeny. Teturam was demonstrated to have an insignificant gonadotropic action and not to potentiate an adverse alcohol action on the male gonads.