[The effect of sulodexide on placental mitochondria function in rats with experimental preeclampsia]. / Vliianie sulodeksida na funktsional'noe sostoianie mitokhondrii platsenty samok krys s éksperimental'noi preéklampsiei.

Substitution of drinking water for 1.8% NaCl in pregnant rats caused a pronounced increase in arterial pressure by 24,3% and urinary protein by 117% to day 21 of pregnancy. State 4 respiration of isolated placental mitochondria in the group of negative control was 3- and 1.5-fold higher with malate/glutamate and succinate as substrates than in placental mitochondria isolated from uncomplicated pregnant animals. This led to a decrease of the respiratory control ratio. These results suggest that development of experimental preeclampsia is accompanied by mitochondrial dysfunction through uncoupling of oxidative phosphorylation. Daily administration of sulodexide to females with experimental preeclampsia (EP) per os at a dose of 30 LE during the whole period of gestation decreased manifestations of the disease as evidenced by a slight increase in blood pressure (by 8,6%) and less pronounces increase in urinary protein (by 58,9%). Sulodexide decreased development of mitochondrial dysfunction in EP rats as shown a decrease of non-stimulated ADP respiration with malate/glutamate and succinate (4.5- and 2.5-fold, respectively) as compared with the negative control group and the corresponding increase in the respiratory control ratio (2.5- and 1.5-fold, respectively). Thus, sulodexide reduces uncoupling of oxidative phosphorylation and enhances the functional activity of mitochondria in EP animals, possibly due to its antioxidant and endotelioprotective effects.

Spatial Memory in the Progeny of Rats Subjected to Different Types of Experimental Preeclampsia.

Spatial memory was studied in 2-month-old offspring of rats subjected to different types of experimental preeclampsia (replacement of drinking water with 1.8% NaCl from day 1 to 21 of gestation or intraperitoneal administration of non-selective NO-synthase inhibitor L-NAME to pregnant rats in a daily dose of 25 mg/kg for 7 days on gestation days 14-20). Spatial memory was evaluated in an elevated 8-arm radial maze. Both types of experimental preeclampsia impaired spatial (long-term and short-term) memory and can be used in the development of drugs correcting negative effects of this pregnancy complication on memory.

Comparison of physical development and rate of formation sensory-motor reflexes offspring of rats with different experimental model of preeclampsia.

Summary: A comparative study of the physical development and the rate of formation of sensory-motor reflexes offspring of rats with experimental preeclampsia (EP) was carried out. In the first experimental group EP was modeled intraperitoneal conduct of L-NAME at a dose of 25 mg/kg from 14 to 21 days of gestation, the second experimental group - the replacement of drinking water by 1.8% sodium chloride solution for the entire period of gestation. In the offspring of both groups, there was a delay of physical development, which was reflected in the later timing of the hair coat development, incisor eruption, pinna detachment as compared to the pups in the control group. It also noted the gap in the formation of sensory-motor reflexes and vestibular reactions. This was manifested in the delayed appearance of the olfactory response, auditory sensitivity, later performing tests «righting reflex¼, «negative geotaxis¼, «aerial righting reflex¼, «cliff avoidance¼, «horizontal wire test¼, «raising the head and forelegs¼, «supporting their bodies on hind legs¼ as compared to the indices of the pups of the female rats with an uncomplicated pregnancy. The most pronounced lag in postnatal development was observed in the offspring of rats with EP, which instead of drinking water was prepared 1.8% sodium chloride during the entire period of gestation. The purpose: To make a comparative study of the impact of ADMA-like preeclampsia (PE) and preeclampsia modeled by the replacement of drinking water consumed by female rats during gestation with 1.8% NaCl solution on the physical development and the rate of the maturation of sensory motor reflexes of their offspring. Methods: The study was performed on three groups of pregnant female rats aged 3-4 months whose original weight was 210-250 g and their pups. They were divided into three groups: 1: Control group including female rats with an uncomplicated pregnancy (n = 6) and their pups (n = 49); 2. Experimental group 1 - pregnant female rats with PE (n = 6) induced by intraabdominal introduction of L-NAME at a dose of 25 mg/kg from 14 to 21 day of gestation (ADMA-like preeclampsia) and their offspring (n = 35); 3. Experimental group 2 - pregnant female rats with PE (n = 6) modeled by the replacement of drinking throughout gestation with 1.8% NaCl solution and their pups. When studying the physical development of the pups we considered the terms of pinna detachment, hair coat development, incisor eruption and the time when they began to open their eyes. To estimate the rate of the maturation of sensory motor reflexes and motor coordination of the pups of the rats with PE we analyzed the time when they started to support their bodies on hind legs, lift their bodies off the floor, crawl, raise their head and forelegs, show the aerial righting reflex and the righting reflex, negative geotaxis, reactions to auditory and olfactory stimuli as well as the time they managed to stay on the horizontal wire. Results: The pups of the female rats with PE of both experimental groups were found to have later pinna detachment, incisor eruption and hair coat development as compared to the indices of the control group. In addition, the offspring of the experimental groups demonstrated a delay in the performance of the following tests: «righting reflex¼, «negative geotaxis¼, «aerial righting reflex¼, «cliff avoidance¼, «horizontal wire test¼, «raising the head and forelegs¼, «supporting their bodies on hind legs¼, «reaction to an olfactory stimulus¼ and «reaction to an auditory stimulus¼ as compared to the indices of the pups of the female rats with an uncomplicated pregnancy. Conclusion: PE induced by the introduction of ADMA to pregnant female rats and by the replacement of drinking water consumed by female rats during gestation with 1.8% NaCl solution causes a delay in physical development, maturation of sensory motor reflexes and vestibular reactions in their offspring.

[Study of Mental Functions Offspring of Rats with Experimental Preeclampsia in Postnatal Ontogenesis].

The postnatal development of offspring's mental functions from rats with experimental preeclampsia caused by the replacement of drinking water by 1.8% sodium chloride solution from the 1st day of pregnancy until delivery was studied. Animals born by females with complicated pregnancy have a high level of anxiety, de- creased, motor, orienting-investigative activity, cognitive impairment in postnatal ontogenesis, compared with the offspring from rats of the control group. This model can be used in research related to the evaluation of animals born to females with the EP, as well as to search for new, effective agents for the purpose-of correcting deviations in nental development in children born to mothers with preeclampsia.

[Gravidaprotective action of phenibut in experimental pre-eclampsia].

It was established that the replacement of drinking water by 1.8% NaCl solution in female rats during pregnancy causes experimental pre-eclampsia (EP), as evidenced by an increase in the blood pressure, proteinuria, and edema in the control group as compared to pregnant female rats with normal drinking regime. Animals with EP exhibited disturbance of vasodilating endothelial function, microcirculation disorder, and increased coagulation and thrombogenic potential of blood. In addition, the group with EP showed evidence of the activation of lipid peroxidation (LPO) due to lower activity of antioxidant enzymes. Daily oral administration ofphenibut (25 mg/kg) in female rats with EP during pregnancy prevents the increase in blood pressure and the severity of proteinuria and edemation. Phenibut improves the vasodilator and antithrombotic endothelial functions, increases uterine blood flow, improves microcirculation, limits LPO, and increases the activity of antioxidant enzymes.

[Comparative study of the effects of new neuroactive amino acid derivatives on the postnatal development of the rat's offspring with experimental preeclampsia].

BACKGROUND: Our aim was to investigate the effect of derivatives of GABA and glutamate on the postnatal development of the offspring of rats with experimental preeclampsia. METHODS: The experiments were performed on 35 albino female rats aged 5-7 months, weighing 220-240 g, and their offspring in the amount of 284 individuals. Experimental preeclampsia was modeled by replacing the drinking water by 1.8% NaCl solution to pregnant females from 7 to 21 days ofgestation. Glutamic acid--compound RSPU-135 at a dose of26mg/kg, GABA derivative - compound RSPU-242 at a dose of 23 mg/kg and the reference drug sulodexide in a dose of 30 mg/kg administered to female orally daily, since the 7th day of gestation prior to delivery. Evaluated the physical development of offspring, sensory-motor reflexes, mental functions. RESULTS: It was found that the experimental preeclampsia causes a delay in physical development and maturation of sensory-motor reflexes in the offspring, as indicated by the later periods of eruption of the incisors and eye opening, response to the emergence of audio and olfactory stimuli, forming vestibular stability and coordination of movements compared to pups from females with physiological pregnancy. Offspring from females with experimental preeclampsia were noted for lagging behind in mental development, as evidenced by the decline of the orienting-exploratory activity, learning and memory, increase of anxiety level. Compound RSPU-135, to a greater extent, improves physical development, increases the rate of maturation of sensory-motor reflexes, RSPU-242--stimulation of cognitive functions, keeping the memory trace, orienting-exploratory, spontaneous locomotor activity, and reduce of anxiety level. CONCLUSION: The neuroactive amino acid derivatives limit the negative effects of experimental preeclampsia on the offspring.