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 analgesic activity of PT1 peptide was maximum after intramuscular injection at a dose of 0.01 mg/kg, which surpassed the analgesic effect of diclofenac at a dose of 1 mg/kg. The anti-inflammatory activity was maximum after intramuscular injection at a dose of 0.0001 mg/kg; a decrease in paw thickness was observed as soon as 2 h after the administration of the PT1 peptide against the background of inflammation development. All tested doses of PT1 peptide showed high anti-inflammatory activity 4 and 24 h after administration. PT1 peptide at a dose of 0.01 mg/kg when injected intramuscularly simultaneously produced high anti-inflammatory and analgesic effects compared to other doses of the peptide. Increasing the dose of PT1 peptide led to a gradual decrease in its analgesic and anti-inflammatory activity; increasing the dose of intramuscular injection to 0.1 and 1 mg/kg is inappropriate.

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 ßIII-tubulin was detected in the newly formed nerve fibers. These histological features are equivalent to the development of peripheral arterial disease in humans, which allows using our model in the search for new therapeutic strategies.

Experimental Approaches to Scar Modeling through Mechanical Skin Damage and Chemical Burn in Sprague Dawley Rats.

Creating of a scar model in laboratory animals is the most acceptable option for the preclinical search of scar treatment. However, due to high skin regeneration rate in laboratory rodents, creating an optimal animal model of scar formation is a challenge. Here we describe five methods for modeling a scar tissue in rats that we have tested. These methods allowed achieving different histopathological features and different stages of skin scar formation.

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

Introduction: 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. Methods: We modeled CAE in awake rats by injecting air into the common carotid artery. Immediately after CAE, animals were either untreated or underwent hyperbaria, oxygen inhalation, heated air inhalation, or helium-oxygen mixture inhalation. Body temperature, locomotor activity, respiratory and cardiovascular parameters were monitored in the animals before CAE modeling, and 3 and 24 h after CAE modeling. Results: After 3 hours of CAE modeling in awake rats, depression of the nervous, cardiovascular and respiratory systems, as well as decreased body temperature were observed. 24 h after CAE modeling multifocal cerebral ischemia was observed. Normobaric helium-oxygen mixture inhalation, on par with hyperbaric treatment, restored body temperature, locomotor activity, respiratory volume, respiratory rate, and blood pressure 3 hours after CAE, and prevented the formation of ischemic brain damage lesions 24 h after CAE. Discussion: Thus, inhalation of a heated oxygen-helium gas mixture (O2 30% and He 70%) immediately after CAE improves the physiological condition of the animals and prevents the foci of ischemic brain damage formation.

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. Metformin therapy at a dose of 250 mg/kg was effective against the background of disturbances in carbohydrate metabolism: animals showed a significant decrease in insulin resistance and TNFα level.

Modeling of Chronic Lung Inflammation in Rats by Repeated Intratracheal Administration of LPS.

A model of a chronic lung inflammation in SPF Sprague-Dawley rats was developed by repeated intratracheal administration of LPS in a dose of 0.4 mg/kg. On day 22 of the study, male rats treated with LPS have relative monocytopenia and reduced mean concentration of hemoglobin in the erythrocyte and the mean platelet volume in comparison with the control animals (saline). Intratracheal administration of LPS induced an inflammatory process in the lungs characterized by focal atelectasis, compensatory emphysematous expansion of subpleural pulmonary acini, focal mononuclear and neutrophilic perivascular and peribronchial infiltration, and minor focal mononuclear and neutrophilic infiltration of the alveolar walls. Against the background of LPS administration, germinal centers appeared in the lymphoid follicles of the white pulp of the spleen, and focal mononuclear infiltration of the tracheal mucosa and/or submucosa was observed in some animals.

Discerning Comparison of 1 and 0.5% Ethylene Glycol in Sprague-Dawley Rats with Modeled Urolithiasis.

A common method of modeling urolithiasis is the use of 1 and 0.75% ethylene glycol, or a combination of ethylene glycol with other lithogens, but too rapid progression of the disease and multiple organ toxicity have been reported. We developed a urolithiasis model in Sprague-Dawley rats, in which the animals received a relatively low concentration of ethylene glycol (0.5%), but for a long-term period (6 weeks) followed by animal observation during the 6-week recovery period. In urine samples, signs of the urolithiasis development were observed starting from the sixth week: the presence of ketones, decrease in diuresis and urine pH; in the blood, urea, protein, and hematocrit were elevated. However, no leukocytes were detected in the urine; in the blood, no shifts in differential leukocyte count and no elevation in ALT, creatinine, cholesterol, and triglycerides were observed, which indicates the absence of multiple organ failure while using 1% ethylene glycol. In addition, the animals receiving 0.5% ethylene glycol were followed up to 12 weeks in contrast to animals receiving 1% ethylene glycol (the experiment in this case was stopped during the third week for ethical reasons).

Anxiolytic Effect of Peptides from Sea Anemone Heteractis crispa, Modulators of TRPV1 and ASIC Channels.

A number of studies confirmed the involvement of transient receptor potential vanilloid (TRPV) and acid-sensing (ASIC) ion channels in the physiological processes associated with the development of anxiety disorders. This makes their ligands new potential anxiolytic agents. We examined the efficacy of two peptides from the sea anemone Heteractis crispa, Hcr 1b-2 and HCRG21, affecting ASIC1a and TRPV1 channels, respectively, in the open field and elevated plus maze tests. According to the obtained data, HCRG21 significantly decreases both the level of anxiety and stimulates the activity of animals at doses of 0.01-1 mg/kg, whereas Hcr 1b-2 has a weak anxiolytic effect only at a dose of 0.1 mg/kg. The pharmacodynamic study showed that the HCRG21 has an anxiolytic effect for 2 h, and its effectiveness is higher than that of the reference drug.

Comparison of Biochemical Parameters and Pathomorphological Changes in Rats Receiving Standard and High-Fat Diets during Modeling of Streptozotocin Diabetes.

The use of a high-fat diet, along with streptozotocin administration, can provide more profound insight into the mechanism of development of complications in diabetes, as well as their treatment. High-fat diet given over 3 weeks before intraperitoneal injection of streptozotocin in a dose of 40 mg/kg promoted the appearance of hyperglycemia in Wistar rats. The biochemical analysis of blood serum revealed increased levels of urea, triglycerides, cholesterol, AST, ALT, and concentration of inorganic phosphates and K+ ions in the high-fat diet group in comparison with the control. Both the biochemical analysis of the blood and histological analysis showed more pronounced abnormalities in rats receiving high-fat diet in comparison with animals receiving standard ration. These changes are the early markers for the development of nephropathy, impaired liver function, and microvascular disorders typical of patients with diabetes mellitus.

Effect of Standard and High-Fat Diets during Modeling of Streptozotocin-Induced Diabetes in Rats on the Development of Complications.

For evaluation of the effect of high-fat diet on the development of diabetic complications, the rats were maintained on standard or high-fat diet. In 3 weeks, diabetes mellitus was modeled by single intraperitoneal injection of streptozotocin. Changes in hematological parameters, physical and biochemical parameters of the urine, and in the development of thermal allodynia were different after 15-week standard and high-fat diets.

Evaluation of the Efficiency of Lubricant Based on Pulmonary Surfactant in Experimental Knee Osteoarthritis in Rats: Analysis of 3D Reconstructions.

We evaluated the efficiency of a lubricant based on a pulmonary surfactant in experimental knee osteoarthritis in rats induced by intraarticular injection of abrasive material that reduces the lubricative properties of the synovial fluid. Experimental substance containing proteins of the pulmonary surfactant exhibiting natural lubricative properties was used as the lubricant. The effectiveness of the substance was analyzed by changes in morphological characteristics of the articular cartilage in 3D reconstruction images of the knee joint obtained by the method of multiple high-precision grinding. It was found that radial thickness of the articular cartilage increased and surface relief index decreased on the 6th and 12th week after administration of the substance containing surfactant proteins, which can indicate partial recovery of the articular cartilage.