Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia.

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.

Retinoprotective Effect of 2-Ethyl-3-hydroxy-6-methylpyridine Nicotinate.

An important task of pharmacology is to find effective agents to improve retinal microcirculation and resistance to ischemia. The purpose of the study is to pharmacologically evaluate the retinoprotective effect of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate in a rat model of retinal ischemia-reperfusion. A retinal ischemia-reperfusion model was used, in which an increase in intraocular pressure (IOP) to 110 mmHg was carried out within 30 min. The retinoprotective effect of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate at a dose of 3.8 mg/kg, in comparison with nicotinic acid at a dose of 2 mg/kg and emoxipine at a dose of 2 mg/kg, was estimated by the changes in the eye fundus during ophthalmoscopy, the retinal microcirculation level with laser Doppler flowmetry (LDF), and electroretinography (ERG) after 72 h of reperfusion. The use of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate prevented the development of ischemic injuries in the fundus and led to an increase in the retinal microcirculation level to 747 (median) (lower and upper quartiles: 693;760) perfusion units (p = 0.0002) in comparison with the group that underwent no treatment. In the group with the studied substance, the b-wave amplitude increased significantly (p = 0.0022), and the b/a coefficient increased reliably (p = 0.0002) in comparison with the group with no treatment. Thus, 2-ethyl-3-hydroxy-6-methylpyridine nicotinate has established itself as a potential retinoprotector.

Study of Anti-inflammatory Activity of a New Non-opioid Analgesic on the Basis of a Selective Inhibitor of TRPA1 Ion Channels.

INTRODUCTION: Nowadays, the group of NSAIDs is used the most widely in order to treat the inflammatory process. But its long-term administration increases the risk of complications of pharmacotherapy. Therefore, today it is urgent to search for new molecules that can selectively block biological targets that directly perceive inflammatory mediators. One of such targets is TRPA1. ZC02-0012, a compound from the group of substituted pyrazinopyrimidinones, which is a selective inhibitor of TRPA1 ion channel. OBJECTIVE: The aim of our study was to study the anti-inflammatory activity of an innovative molecule under the laboratory code ZC02-0012 from the group of selective inhibitors of TRPA1 ion channel. MATERIALS AND METHODS: Anti-inflammatory activity of ZC02-0012 was studied on the model of acute exudative inflammation of the paw in response to subplantar injection in the right hind paw of mice with 0.02 ml of 2% formaldehyde solution. The mass of the paw was measured after 4 hours (peak edema) after phlogistic injection. The test substance and the reference drug was administered intragastrically or intramuscularly 45 minutes before the injection of formaldehyde solution. The presence and intensity of antiinflammatory activity was judged by the inhibitory effect, represented in percent. RESULTS AND DISCUSSION: Selective inhibitor of the TRPA1 ion channel ZC02-0012 revealed the anti-inflammatory activity at doses of 3 and 9 mg/kg, its intensity is comparable to diclofenac sodium. CONCLUSION: The selective inhibitor of the ion channel TRPA1, a substance under code ZC02-0012, has an anti-inflammatory activity comparable with diclofenac sodium.