Non-conventional toxin WTX and its disulfide-fixed synthetic fragments: Interaction with nicotinic acetylcholine receptors and reduction of blood pressure.

Non-conventional snake venom toxins, such as WTX from the cobra Naja kaouthia, are three-finger proteins containing a fifth disulfide bond in the N-terminal polypeptide loop I and inhibiting α7 and muscle-type nicotinic acetylcholine receptors (nAChRs). Because the central polypeptide loop II of non-conventional toxins plays an important role in their biological activity, we synthesized several WTX loop II fragments with two cysteine residues added at the N- and C-termini and oxidized to form a disulfide bond. The inhibition by peptides of several nAChRs subtypes was investigated using different methods and the effects of peptides on the rat arterial pressure and heart rate were analyzed.

Comparison of the Results of Modeling Pulmonary Fibrosis in Sprague Dawley Rats by Intratracheal Administration of Bleomycin in the Form of Sulfate and Chloride at a Dose of 3 mg/kg.

: Intratracheal administration of bleomycin (BLM) to laboratory rodents is a standard, widely used technique used to model pulmonary fibrosis (PF). BLM, as a modeling agent, is produced mainly in the form of two salts-sulfate and chloride. We compared the results of modeling PF in SD rats by intratracheal administration of BLM sulfate and BLM chloride.

Development and Worsening of Hypertension with Age in Male Wistar Rats as a Physiological Model of Age-Related Hypertension: Correction of Hypertension with Taxifolin.

To preclinically study the effectiveness of new antihypertensive drugs, various animal hypertension models are used. However, most of them do not correspond to primary hypertension, which develops in people with age. We used male Wistar rats of 4, 10, 12 and 18 months old.

Experimental Model of Cerebral Arterial Air Embolism in Conscious Rats.

In this work, an optimal air supply mode was selected to create a model of cerebral arterial air embolism (CAAE) on conscious male Sprague-Dawley rats (n=49). The efficacy of the selected model (administration of 100 μl/kg of air at a rate of 10 μl/min with an infusion pump) was determined by changes in serum biochemical parameters (cholesterol, alkaline phosphatase, inorganic phosphates, AST, and triglycerides), impaired motor functions in the Rotarod test, and visual assessment of the ischemic foci (staining of frontal sections with 1% triphenyltetrazolium chloride solution) at different terms after AAE. The model of AAE created by us confirmed impairment of coordination and motor function in conscious animals and reproduced the lethal consequences of this condition.

Modeling of Cerebral Ischemic Stroke in Conscious Rats via Arterial Air Embolization.

The etiological factor of cerebral ischemia in the vast majority of cases is vascular embolism. In the present study we investigated embolism caused by atmospheric air bubbles injected into the internal carotid artery of conscious rats. Immediately after embolism modeling, behavioral abnormalities were observed in the animals, and after 24 h, foci of brain damage were detected.

Mutagenesis of the Peptide Inhibitor of ASIC3 Channel Introduces Binding to Thumb Domain of ASIC1a but Reduces Analgesic Activity.

Acid-sensing ion channels (ASICs), which act as proton-gating sodium channels, have garnered attention as pharmacological targets. ASIC1a isoform, notably prevalent in the central nervous system, plays an important role in synaptic plasticity, anxiety, neurodegeneration, etc. In the peripheral nervous system, ASIC1a shares prominence with ASIC3, the latter well established for its involvement in pain signaling, mechanical sensitivity, and inflammatory hyperalgesia.

Study of PT1 Peptide Analgesic and Anti-Inflammatory Activity on a Local Inflammation Model in Mice CD-1.

PT1 peptide isolated from the venom of spider Geolycosa sp. is a modulator of P2X3 receptors that play a role in the development of inflammation and the transmission of pain impulses. The anti-inflammatory and analgesic efficacy of the PT1 peptide was studied in a model of complete Freund's adjuvant-induced paw inflammation in CD-1 mice.

The Study of TRPV1 Channels of the Central Nervous System and Their Effect on Anxiety in ICR Mice.

The TRPV1 channel is actively involved in various neuronal processes and is found in various structures of the nervous system, including peripheral and central neurons, sensory ganglia, spinal cord, and various parts of the brain. Due to its ability to respond to various stimuli, TRPV1 can have a significant impact on the body's responses to stress. Studies indicate the involvement of TRPV1 in the regulation of anxiety behavior.

Pathological Changes in the Gastrocnemius Muscle throughout Hind Limb Ischemia Modeling in Rats.

We present a two-stage model for the study of chronic hind limb ischemia in rats. In the area of ischemia, sclerotic changes with atrophic rhabdomyocytes and reduced vascularization were revealed. CD31 expression in the endothelium increased proportionally to the number of vessels in the ischemic zone, and at the same time, focal expression of βIII-tubulin was detected in the newly formed nerve fibers.

Effect of a helium and oxygen mixture on physiological parameters of rats with cerebral arterial air embolism.

Cerebral arterial air embolism (CAE) is a serious and potentially dangerous condition that can interrupt the blood supply to the brain and cause stroke. One of the promising gas mixtures for emergency treatment of air embolism is an oxygen-helium mixture. We modeled CAE in awake rats by injecting air into the common carotid artery.

Unified Methodology for the Primary Preclinical In Vivo Screening of New Anticoagulant Pharmaceutical Agents from Hematophagous Organisms.

The development of novel anticoagulants requires a comprehensive investigational approach that is capable of characterizing different aspects of antithrombotic activity. The necessary experiments include both in vitro assays and studies on animal models. The required in vivo approaches include the assessment of pharmacokinetic and pharmacodynamic profiles and studies of hemorrhagic and antithrombotic effects.

Characterization of Risk Factors for Modeling of Type 2 Diabetes Mellitus Induced by a High-Fat Diet in C57BL/6 Mice.

Type 2 diabetes mellitus develops due to a combination of genetic and environmental factors. C57BL/6 mice prone to obesity and leptin resistance were kept on a high-fat diet for 21 weeks. The animals showed a significant increase in fasting and postprandial glucose levels and body weight, the development of insulin resistance, and by week 18, an increase in the serum TNFα level.

Nocistatin and Products of Its Proteolysis Are Dual Modulators of Type 3 Acid-Sensing Ion Channels (ASIC3) with Algesic and Analgesic Properties.

The neuropeptide nocistatin (NS) is expressed by the nervous system cells and neutrophils as a part of a precursor protein and can undergo stepwise limited proteolysis. Previously, it was shown that rat NS (rNS) is able to activate acid-sensing ion channels (ASICs) and that this effect correlates with the acidic nature of NS. Here, we investigated changes in the properties of rNS in the course of its proteolytic degradation by comparing the effects of the full-size rNS and its two cleavage fragments on the rat isoform 3 ASICs (ASIC3) expressed in X.

Novel BRICHOS-Related Antimicrobial Peptides from the Marine Worm : Transcriptome Mining, Synthesis, Biological Activities, and Therapeutic Potential.

Marine polychaetes represent an extremely rich and underexplored source of novel families of antimicrobial peptides (AMPs). The rapid development of next generation sequencing technologies and modern bioinformatics approaches allows us to apply them for characterization of AMP-derived genes and the identification of encoded immune-related peptides with the aid of genome and transcriptome mining. Here, we describe a universal bioinformatic approach based on the conserved BRICHOS domain as a search query for the identification of novel structurally unique AMP families in annelids.

Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of Osteoarthritis.

Progressive articular surface degradation during arthritis causes ongoing pain and hyperalgesia that lead to the development of functional disability. TRPA1 channel significantly contributes to the activation of sensory neurons that initiate neurogenic inflammation and mediates pain signal transduction to the central nervous system. Peptide Ms 9a-1 from the sea anemone is a positive allosteric modulator of TRPA1 and shows significant anti-inflammatory and analgesic activity in different models of pain.

C-Terminal Region of Caveolin-3 Contains a Stretch of Amino Acid Residues Capable of Diminishing Symptoms of Experimental Autoimmune Encephalomyelitis but Not Rheumatoid Arthritis Modeled in Rats.

A short synthetic peptide from the C-terminal part of the caveolin-3 structure was tested for experimental autoimmune encephalomyelitis (EAE) treatment in rats. The structure-function similarity established between the novel synthetic peptide of pCav3 and the well-known immunomodulator immunocortin determined pCav3's ability to reduce EAE symptoms in Dark Agouti (DA) rats injected with pCav3 (500 µg/kg). pCav3 was found to interfere with the proliferation of lymphocytes extracted from the LNs of DA rats primed with homogenate injection, with IC = 0.

Anti-smoking drugs cytisine and varenicline reduce cardiac reperfusion injury in rat model of myocardial ischemia.

Evidence to date indicates that activation of nicotinic acetylcholine receptors (nAChRs) can reduce cardiac injury from ischemia and subsequent reperfusion. The use of nAChR agonists in various animal models leads to a reduction in reperfusion injury. Earlier this effect was shown for the agonists of α7 nAChR subtype.

Control of postprandial hyperglycemia by oral administration of the sea anemone mucus-derived α-amylase inhibitor (magnificamide).

Diabetes mellitus is a serious threat to human health in both developed and developing countries. Optimal disease control requires the use of a diet and a combination of several medications, including oral hypoglycemic agents such as α-glucosidase inhibitors. Currently, the arsenal of available drugs is insufficient, which determines the relevance of studying new potent α-amylase inhibitors.

Selective targeting of α7 nicotinic acetylcholine receptor by synthetic peptide mimicking loop I of human SLURP-1 provides efficient and prolonged therapy of epidermoid carcinoma .

α7-Type nicotinic acetylcholine receptor (α7-nAChR) promotes the growth and metastasis of solid tumors. Secreted Ly6/uPAR-Related Protein 1 (SLURP-1) is a specific negative modulator of α7-nAChR produced by epithelial cells. Here, we investigated mechanisms of antiproliferative activity of recombinant SLURP-1 in epidermoid carcinoma A431 cells and activity of SLURP-1 and synthetic 21 a.

Synthetic Peptide Fragments of the Wtx Toxin Reduce Blood Pressure in Rats under General Anesthesia.

Previously, it was shown that the non-conventional toxin WTX from the venom of the cobra Naja kaouthia, when administered intravenously, caused a decrease in blood pressure (BP) and an increase in heart rate (HR) in rats [13]. To identify the site of the toxin molecule responsible for these effects, we studied the influence of synthetic peptide fragments of the WTX on BP and HR in normotensive male Sprague-Dawley rats under general anesthesia induced by Telazol and Xylazine. It was found that peptides corresponding to the WTX central polypeptide loop, stabilized by a disulfide bond, at intravenous injection at concentrations from 0.

Analogs of 6-Bromohypaphorine with Increased Agonist Potency for α7 Nicotinic Receptor as Anti-Inflammatory Analgesic Agents.

Hypaphorines, tryptophan derivatives, have anti-inflammatory activity, but their mechanism of action was largely unknown. Marine alkaloid L-6-bromohypaphorine with EC of 80 μM acts as an agonist of α7 nicotinic acetylcholine receptor (nAChR) involved in anti-inflammatory regulation. We designed the 6-substituted hypaphorine analogs with increased potency using virtual screening of their binding to the α7 nAChR molecular model.

Di-, tetra-, and perhydropyrrolo[1,2-]imidazoles: The Methods of Synthesis and Some Aspects of Application.

The review summarizes and systematizes the literature data on the synthesis and some aspects of application of pyrrolo[1,2-]imidazoles. Synthetic approaches are grouped according to the degree of saturation of the product pyrroloimidazole ring. The bibliography of the review includes 110 sources over the last 15 years.