THE EFFECT OF THE ARTICHOKE LEAVES EXTRACT ON THE POSTNATAL DEVELOPMENT OF OFFSPRING OF FEMALE RATS WITH THE ALCOHOLIC PLACENTAL DYSFUNCTION

The experimental research of the artichoke (Cynara scolymus) leaves extract (ALE) influence on the postnatal development of the Ist generation rats born by female rats with the ethanol-induced placental dysfunction (PD) has been conducted. It has been found that the therapeutic and preventive regimen of ALE and the reference medicine Solcoseryl from the 14th to the 19th day of gestation (on the background of introduction of 40% ethanol solution in the dose of 4 g/kg) reduced the level of death in infant rats: ALE in 2.4 times and Solcoseryl in 1.6 times compared to the untreated control. The medicines studied caused a significant weight gain in rats compared to the control pathology group. From the 1st to 14th days of the experiment the weight gain caused by ALE was more significant. The difference in the efficacy of the medicines was not further observed. Introduction of ALE and Solcoseryl also promoted the correction of pathological deviations in the postnatal development of infant rats. Moreover, ALE showed a higher activity compared to Solcoseryl. Therefore, the data obtained allow to recommend ALE for the preventive correction of alcoholic embryopathy developed on the background of PD.

A lcoholism is referred to the medical and social risk factors of the placental dysfunction (PD) development. Recently increase of alcohol consumption by pregnant women has been observed; as a result, the number of alcoholic PD development cases increases. For example, official statistical data show that the share of such women in the USA is 3-10%, in Ukraine is about 10% [4,7,10]. It is known that alcohol can cross the placental barrier, accumulate in the amniotic fluid and have not only the embryolethal, teratogenic, but also the general toxic effect on a fetus [6,8,11]. It results in formation of the fetal alcoholic syndrome, which is characterized with growth retardation, mainly expressed within the first months and years of the postnatal period, delay in physical and mental development of children, etc. [3,4,6].
A product of the plant origin "Chophytol" (Lab. Rosa-Phytophar-ma, France) containing the artichoke (Cynara scolymus) leaves extract (ALE) is used in obstetrics for prevention and treatment of PD of various genesis [3,5,9]. The results of the previous research show that ALE has expressed the gravidоprotective action under acute ethanol intoxication of rats [1].
The aim of the work was to study the effect of ALE on the postnatal development of infant rats of the 1 st generation born by female rats with alcoholic PD.

Materials and Methods
Alcohol-induced PD was initiated with intragastric introduction of 40% ethanol solution in the dose of 4 g/kg to white nonlinear female rats weighting 180-220 g, in the fetal phase from the 15 th to the 19 th days of pregnancy [2]. The artichoke leaves extract was introduced in the medical and preventive regimen from the 14 th to the 19 th days of the intragastri-gal gestation in the conditionally therapeutic dose of 50 mg/kg, and the reference medicine Solcoseryl (Valleant pharmaceutical Switselend GmbH, batch 827509), a natural medicine as well, was introduced in the dose of 0.56 ml/kg, intravenously following the same scheme. Females rats were kept antepartum to study the postnatal development of the 1-st generation. The new-born rats kept under usual conditions characteristic for this type of animals were observed within 30 days.
Viability and the somatosexual development of the 1 st generation offspring were estimated by the following parameters: the level of the postnatal lethality, the body weight dynamics on the 1 st , 4 th , 7 th , 14 th , 21 st and 28 th days of observation, pinna detachment and hear-coat covering on the 4 th day; eruption of incisors on the 7 th day; eyes opening on the 14 th day; opening of the vagina and testicles lowering on the 30 th day.
Statistical analysis of the data obtained was conducted using the parametric methods (Student`s t-test with Bonferroni adjustment, the significance value р ≤ 0.05) with

Results and Discussion
The experimental results are given in Table 1.
It has been determined that lethality of infant rats of the intact animals group in the postnatal period increased before the 21 st day of observation. The total lethality by the end of the experiment reached 8.5%. Ethanol introduced to the pregnant rat females of the control pathology group resulted in 3 times greater probability of new-born rats lethality at all times of the experiment in relation to the intact control. Therefore, vitality of such new-born rats within one month of the postnatal period is almost 1.3 times lower compared to new-borns of healthy females.
In the group of animals receiving ALE the offspring lethality reduced by an average 2.4 times compared to the control pathology group and was almost the same as in new-borns of healthy females. At the same time the quantity of dead infant rats born by female rats treated with the reference medicine Solcoseryl was only 1.6 times less than in untreated animals. The lethality index of Solcoseryl was 1.5 times greater than the one of the medicine under research.
Starting from the first day of birth the body weight dynamics was registered ( Table 2). The initial body weight of infant rats in the group of the intact control on the first day after their birth was 5.96 g. Fast and considerable increase of weight was observed un-til the 30 th day of the experiment. On the background of the prenatal alcoholization of pregnant females the weight of infant rats probably reduced starting from the 1 st to the 30 th day of the postnatal development compared to the group of healthy animals. Thus, on the 1 st and the 4 th day of observation it was 1.34 g less; on 7 the th day -1.87 g less, on the 14 th day -4.94 g less, on the 21 st day -9.52 g less, on 30 th day -14.7 g less. Besides, increase of the body weight of infant rats in the control pathology group was slower than in animals of the intact control group.
The body weight of infant rats born by female rats receiving ALE was almost the same as of infant rats of intact animals. Introduction of Solcoseryl also resulted in probable increase of the body weight Table 1 The

effect of the artichoke leaves extract on lethality of infant rats of the first generation born by female rats with the placental dysfunction caused by ethanol introduction
Group of animals Notes: 1) * -statistically significant difference in relation to the animals of the intact control group, р ≤ 0.05; 2) ** -statistically significant difference in relation to the animals of the control pathology group, р ≤ 0.05.

Table 2
The Preventive introduction of ALE resulted positively on the rates of somatosexual development of infant rats. The corresponding indices are given in Table 3.

body weight dynamics of infant rats of the 1 st generation born by female rats with the placental dysfunction caused by ethanol introduction (X±S x ) (n=59)
Unlike healthy animals the physiological signs of development significantly slowed down in infant rats of the control pathology group. 2. The artichoke leaves extract accelerates the somatosexual state of the first generation offspring by such parameters as eruption of incisors, opening of the vagina and has an advantage over the reference medicine Solcoseryl.
3. The results obtained allow to recommend the artichoke leaves extract to be used in complex therapy for preventing the fetal alcoholic syndrome as a complication of the alcoholic placental dysfunction. Notes: 1) * -statistically significant difference in relation to the animals of the intact control group, р ≤ 0.05; 2) ** -statistically significant difference in relation to the animals of the control pathology grouр, р ≤ 0.05; 3) *** -statistically significant difference in relation to the animals injected with Solcoseryl, р ≤ 0.05.