Preeclampsia is a severe disease of late pregnancy. Etiological factors and a pathogenetic pattern of events still require significant clarification, but it is now recognized that a large role is played by placentation disorders and emerging endothelial dysfunction. The administration of short-chain peptides mimicking the spatial structure of the B erythropoietin chain may become one of the directions of searching for new drugs for preeclampsia prevention and therapy. Simulation of ADMA-like preeclampsia in Wistar rats was performed by the administration of a non-selective NOS blocker L-NAME from the 14th to 20th day of pregnancy. The administration of the pHBSP at the doses of 10 µg/kg and 250 µg/kg corrected the established morphofunctional disorders. The greatest effect was observed at a dose of 250 µg/kg. There was a decrease in systolic and diastolic blood pressure by 31.2 and 32.8%, respectively (p < 0.0001), a decrease in the coefficient of endothelial dysfunction by 48.6% (p = 0.0006), placental microcirculation increased by 82.8% (p < 0.0001), the NOx concentration was increased by 42,6% (p = 0.0003), the greater omentum edema decreased by 11.7% (p = 0.0005) and proteinuria decreased by 76.1% (p < 0.0002). In addition, there was an improvement in the morphological pattern of the fetoplacental complex and the ratio of BAX to Bcl-2 expression which characterizes the apoptotic orientation of the cells.
Using the combined application of L-arginine with HMG-Co-A reductase inhibitors simvastatin, atorvastatin, rosuvastatin and nanoparticulated rosuvastatin on the background of modeling of sepsis-induced disease through the introduction of strain 603 Staphylococcus aureus shows endotelio- and cardioprotective effects, manifesting itself in preventing the proliferation of endothelial dysfunction coefficient (CED), adrenoreactivity, maintenance of myocardial reserve and the normalization of biochemical markers values (Total NO, eNOS expression, C-reactive protein, IL-6, TNF). In this case, the combined therapy was so effective that the values obtained thereunder did not differ from those obtained from control animals.
L-arginine (200 mg/kg), vitamin B(6) (2 mg/kg), and folic acid (0.2 mg/kg) exert a protective effect on endothelial function in L-NAME-induced NO deficiency in male and pregnant female Wistar rats. Combined administration of these agents effectively prevented the development of endothelial dysfunction and L-NAME-induced preeclampsia.
Использование ингибиторов ГМГ-Ко-А-редуктазы симвастатина, аторвастатина, розувастатина и нанопартикулированного розувастатина на фоне моделирования эндотоксининдуцированной патологии введением штамма 603 Staphylococcusaureus приводит к развитию дозозависимого эндотелиопротективного действия, выражающегося в нормализации КЭД, предотвращению повышения адренореактивности и исчерпания миокардиального резерва, а также нормализации биохимических маркеров воспаления (С-реактивный белок) и уровня провоспалительных цитокинов. При этом обнаружена положительная динамика конечных продуктов NO и экспрессии eNOS. Ключевые слова: дисфункция эндотелия, ингибиторы ГМГ-Ко-А-редуктазы, эндотоксин.
Denisyuk T.A. ENDOTHELIO-AND CARDIOPROTECTIVE EFFECTS OF HMG-Co-A REDUCTASE IN ENDOTOKSIN-INDUCING ENDOTELIAL DYSFUNCTION
Intragastric methionine (3 g/kg daily for 7 days) elevates homocysteine concentration and increases the endothelial dysfunction coefficient. This protocol of methionine treatment is an adequate model of hyperhomocysteine-induced endothelial dysfunction and can be used for studies of the endothelio- and cardioprotective effects of drugs.
Purulent meningitis (PM) is a severe disease, characterized by high mortality and a formation of a residual neurological deficit. Loss of treatment of PM leads to the lethal outcome in 100% of cases. In addition, death and the development of residual neurological complications are possible despite adequate therapy. The aim of the study was to evaluate the cerebroprotective effects of a new pharmacological compound 2-ethyl-6-methyl-3-hydroxypyridine-2,6-dichlorophenyl(amino)phenylethanoic acid (EMHDPA) on the bacterial purulent meningitis in a model of experimental pneumococcal meningitis. Meningitis was simulated by intrathecal injection of the suspension containing Streptococcus pneumoniae at the concentration of 5 × 109 CFU/mL. The cerebroprotective effect was evaluated by survival rates, the severity of neurological deficit, investigatory behaviors, and results of short-term and long-term memory tests. The group administered with EMHDPA showed high survival rates, 80%. Animals treated with the studied compound showed a higher clinical assessment of the rat health status and specific force, and a lesser intensity of neurological deficit compared to the control group (p < 0.05). Locomotor activity of the animals treated with EMHDPA was significantly higher compared to the control group (p < 0.05). There is a decrease in the activity of all estimated indicators of oxidative stress in the group administered with 2-ethyl-6-methyl-3-hydroxypyridine-2,6-dichlorophenyl(amino)phenylethanoic acid relative to the control group: a decrease in the activity of catalase—17%, superoxide dismutase—34%, malondialdehyde and acetylhydroperoxides—50%, and nitric oxide—85% (p < 0.05). Analysis of the data obtained during the experiment leads to the conclusion about the effectiveness of 2-ethyl-6-methyl-3-hydroxypyridine-2,6-dichlorophenyl(amino)phenylethanoic acid in the treatment of the experimental PM.
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