Intragastric Tube Research Articles

An experimental model of liver echinococcosis in laboratory rats to study the effectiveness of anthelmintic drugs

BACKGROUND: The introduction into clinical practice of drug therapy with anthelmintic drugs from the carbamate-benzimidazole group has reduced the need for aggressive surgical interventions in the initial stages of parasitic cyst development. However, no consensus has been reached in which cases and for what size of cysts the use of monotherapy with carbamate benzimidazoles will be sufficient and in which cases a combination of surgical and therapeutic treatment methods is necessary. Experimental studies with human participants are impossible to solve this problem. AIM: To evaluate the proximity of the developed experimental model of liver echinococcosis to real clinical practice, including the response to the use of carbamate benzimidazoles. MATERIALS AND METHODS: Modeling of liver echinococcosis in laboratory animals was performed by suturing a part of an echinococcal bladder (Echinococcus granulosus) to the liver capsule. The model provides a high survival percentage of laboratory animals, in which after 60 days a typical hydatid cyst forms in the liver. The effects of albendazole and praziquantel were studied using this echinococcus model. One group of animals (n = 10) received albendazole through an intragastal tube for 28 days and the other (n = 10) received praziquantel for 15 days, after which the animals were autopsied. RESULTS: When using albendazole, destructive changes were microscopically determined in the structure of the walls of the echinococcal cyst on day 28 of therapy. Similar changes were observed when using praziquantel; however, they were characterized by more massive cellular infiltration of all cyst layers. CONCLUSIONS: The developed experimental model of liver echinococcosis in laboratory animals allowed us to experimentally examine the effect of various drugs on the larval stages of E. granulosus development and evaluate their effectiveness.

The effect of aluminum- and silicon-containing enterosorbent on the thymic cellular composition in mice kept under two-week all-night lighting

Background. Continuous lighting contributes to the development of desynchronosis, which is stressful for the body. As a result, the normal functioning of the immune system is disrupted, which in turn can shift the physiological balance towards pathology and endotoxemia. It is relevant to develop innovative drugs based on a sorbent matrix, which can be modified with biologically active molecules that extendedly leave the sorbent surface. At the same time, the sorbent retains the properties of a detoxifier, fixing toxic agents on the surface and removing them from the body, which helps restore the internal environment and normalizes the overall reactivity of the body in extreme conditions.The aim. To study the effect of aluminum- and silicon-containing enterosorbent (based on aluminum oxide and polydimethylsiloxane) on the cellular composition of the thymus and the distribution of thymocytes in the organ according to the cell cycling state in C57Bl/6 mice kept under the all-night lighting.Materials and methods. Animals received sorbent (0.665 g per 1 kg of body weight in 200 μl of distilled water) through an intragastric tube once a day for 14 days against the background of continuous lighting. Intact mice and placebo animals composed control group. We used flow cytometry to assess the percentage of CD3hi and CD3low lymphocytes of the thymus, the CD3low/CD3hi ratio, viability and distribution of cells across according to the cell cycling state.Results. Continuous lighting inhibited the differentiation and maturation of young CD3low lymphocytes into mature forms of CD3hi, reduced the proliferation of thymic epithelial cells, and activated apoptosis of lymphocytes and epithelial cells in the organ. The introduction of the sorbent restored the content and viability of young CD3low lymphocytes and contributed to the preservation of the viability and proliferation of thymic epithelial cells.Conclusion. Using an enterosorbent based on aluminum oxide and polydimethylsiloxane under conditions of continuous lighting helps maintain the functional activity of the thymus, preventing its involution, and is advisable against the background of circadian disruption.

“The end of the era of antibiotics” — myth or reality: what the past COVID-19 pandemic has shown

BACKGROUND: During the coronavirus disease 2019 pandemic, the sale of antimicrobials (AMPs) in the pharmacy network and their purchases by healthcare facilities of the Russian Federation have significantly increased. Microbiological monitoring conducted at the City Clinical Hospital No. 67 named after L.A. Vorokhobov of the Moscow Health Department in 2020–2021 revealed an urgent problem: gram-negative bacteria, which are dominated by multidrug-resistant (MDR) strains, are now mainly isolated from patients with healthcare-associated infections (HAIs). Pharmacoeconomic studies have shown that the cost of one course of targeted antibiotic therapy for HAIs can increase by 6–12 times compared with a similar course of therapy in the absence of nosocomial MDR and extensively drug-resistant (XDR) pathogens.
 AIM: To increase the effectiveness of preventive measures aimed at preventing the spread of hospital-acquired pathogen strains in the intensive care unit (ICU) using effective bacteriophages against MDR strains of Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter baumannii, which were selected in accordance with an individualized algorithm.
 MATERIALS AND METHODS: The study included two groups, totaling 20 patients, who were on prolonged mechanical ventilation in the ICU of City Clinical Hospital No. 67 named after L.A. Vorokhobov of the Moscow Health Department in 2022. The second group received 20 mL of bacteriophages via an intragastric tube for five consecutive days. The concept of a personalized approach to phage therapy for various forms of HAIs caused by nosocomial MDR pathogens in patients of a multidisciplinary hospital has been proposed and tested.
 RESULTS: With this medical technology, the effectiveness of phage therapy for various nosological forms of HAIs caused by nosocomial MDR and XDR strains increased by 30%, and the effectiveness of the initial antibiotic therapy regimen was ≥70%. The economic effect of the combination of antibiotic therapy and phage therapy (booster therapy) amounted to more than 3 million rubles compared with the use of AMP alone for treating patients with HAIs caused by nosocomial MDR/XDR strains.
 CONCLUSIONS: Booster therapy as a variant of IIB therapy reduces the cost of treatment of AMPs of various forms of HAIs by ≥2.5 times compared with AMPs alone.

Lanthanum Hydroxide and Chronic Kidney Disease Mineral and Bone Disorder: A Rat Model.

To investigate the pharmacological effects and molecular mechanisms of lanthanum hydroxide(LH) on ectopic mineralization of soft tissue and abnormal bone in rats with acute kidney injury(AKI). Wistar rats were modeled by 5/6 nephrectomy. After the operation, the rats were divided into different groups, the biochemical indexes of serum collected at different times. LH was administered by intragastric tube at doses of 0.4, 0.2, and 0.1g/kg, respectively. Rats were sacrificed in the 16th week after LH treatment. Observation of pathological changes in tissues were made by specific staining. Western Blot, Real-Time Quantitative PCR, and immunohistochemistry techniques were used to detect the impact on pathway-related proteins. Compared with the control group (no LH administered), the serum phosphate level of the LH group was significantly reduced (p<0.01), calcification of the thoracic aorta was reduced (p<0.05, p<0.01) (Serum biochemical tests before dosing and during drug treatment cycles), renal fibrosis was improved (p<0.01), nuclear entry of nuclear factor kappa-B (NF-κB) was reduced (p<0.01), and the expression of the smooth muscle protein 22α (SM22α) was significantly increased (p<0.01). The expression of osteogenic marker genes was decreased. In addition, compared with the controls, the receptor activator for nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) ratio of the femur in the model group was increased (p<0.05). LH can inhibit the occurrence and development of vascular calcification and bone abnormalities in AKI rats by inhibiting the NF-κB and RANKL/OPG signaling pathways.

The study of acute and subchronic oral toxicity of medicinal drug «Enrocolitrim» on laboratory animals

Relevance. The results of the study of the oral toxicity of the medicinal product for veterinary use «Enrocolitrim» on laboratory rodents are presented. Studies of acute toxicity in mice and rats with the determination of the hazard class are described, as well as data on the study of subchronic toxicity of the drug for 14 days in laboratory rats are presented.Methods. To determine the acute toxicity of the drug, 36 outbred rats and 50 outbred mice were used. «Enrocolytrim» was administered using an intragastric tube at doses that allow revealing a dose-dependent effect to assess LD50. Toxicity parameters were calculated according to the method of Kerber, Miller and Teintner, the nature and severity of signs of animal intoxication were visually assessed for 14 days. In a subchronic experiment, the study drug «Enrokolitrim» was studied on 40 outbred rats, of which 3 experimental and 1 control groups were formed. During the experiment, the rodents were weighed, signs of intoxication were recorded, and blood samples were taken for morphological and biochemical analyzes. Dead and euthanized animals were subjected to autopsy.Results. The obtained LD50 values with a single oral administration of the drug «Enrocolitrim» to rats and mice allowed it to be assigned the 4th hazard class – lowh–azard substances (GOST 12.1.007-76). In a subchronic 14-day experiment on rats, it was found that the dose of «Enrocolitrim» 1243 mg/kg with intragastric administration is toxic, and doses of 621.5 mg/kg and 248.6 mg/kg are inactive (safe).

Structural changes in testes of Streptozotocin induced diabetic rats and possible protective effect of royal jelly: light and electron microscopic study

ABSTRACT Diabetes mellitus (DM) is one of the most common metabolic diseases causing damage in many organs in the body including the testes. Royal Jelly (RJ) is one of the honey bee products that has antioxidant, anti-inflammatory and antidiabetic properties. This study was performed to evaluate the changes in the microscopic structure of the testes in Streptozotocin (STZ)-induced diabetic rats, and the possible protective role of RJ. 60 adult male albino rats were divided into three groups. Group I Control group, Group II STZ group, and Group III STZ+RJ group. Group II received a single dose of STZ (50 mg/kg) by intraperitoneal injection. Group III received a single dose of STZ as in the second group then received RJ orally by intragastric tube in dose of (100 mg/kg/day) for 4 weeks after confirmation of diabetes. Light and electron microscopic studies were performed. Group II revealed marked structural changes affecting seminiferous tubules with sever reduction in germinal epithelium and loss of mature spermatozoa in their lumina. The interstitial tissue revealed degenerated Leydig cells and congested blood vessels. Mallory trichrome stained section of group II revealed marked increase in the amount of collagen fibers. Group III revealed highly preserved testicular architecture almost near to that appeared in the control group except few tubules that were damaged. In conclusion, RJ protected the testicular structure from the damaging effect of diabetic oxidative stress through its antioxidant effect thus preserving male fertility.

Effect of a sorbent composition based on aluminum oxide and polydimethylsiloxane on the reproductive system of &lt;i&gt;db/db&lt;/i&gt; female mice with genetically determined obesity and type 2 diabetes mellitus

Metabolic syndrome, obesity, type 2 diabetes mellitus are characterized by the accumulation of toxic metabolic products in the internal environment of the organism. The development of innovative medicines based on a sorbent matrix modified with biologically active molecules remains relevant. The sorbent composition from aluminum oxide and polydimethylsiloxane is considered promising. The aim of the study. To investigate the effect of the sorbent composition from aluminum oxide and polydimethylsiloxane on the uterus and ovaries of db/db mice with obesity and type 2 diabetes mellitus. Materials and methods. The sorbent composition (0.665 g/kg in 200 μl of distilled water) was administered to 14-week-old animals through an intragastric tube once a day for 7 days. The comparison groups were female rats injected with placebo (daily intragastrical administration of 200 µl of water for 7 days) and intact animals. Digital images of light-optical preparations stained with hematoxylin and eosin were processed using Image-Pro Plus 4.1 software. In the ovaries, the numerical density of primordial, primary, secondary follicles and corpus luteum was determined. The width of the uterus layers, the diameters of the blood and lymphatic vessels, the width of the interstitial fissures in both organs were measured. The statistical significance of differences was determined using the Mann – Whitney test. Results. In the myometrium and endometrium of the uterus of db/db mice, dilatation of arteries, veins, lymphatic vessels and edema were noted due to the accumulation of tissue fluid in the interstitium layers. There were no tertiary follicles in the ovaries. The introduction of the sorbent composition contributed to a decrease in the diameters of arteries, veins, lymphatic vessels of the uterus, a decrease in edema in both organs due to the narrowing of the prelymphatic slits, and stimulated an increase in the numerical density of secondary follicles. Conclusion. A corrective effect of the sorbent composition of aluminum oxide and polydimethylsiloxane on prelymphatic slits, blood and lymphatic vessels in the uterus and ovaries in db/db mice with obesity and type 2 diabetes mellitus was revealed.

Assessment of Antidiabetic and Cyto-Regenerative Activity of Ficus carica through Gene Expression Analysis in Diabetic Rat Model

Diabetes mellitus is a metabolic disease of the endocrine system, characterized by chronic hyperglycemia resulting from insulin resistance or defective insulin production. Among the complementary and alternative medicines, diet-based approaches are gaining popularity worldwide for the management of it. Ficus carica, one of the oldest plants cultivated on the earth, is rich in phytochemicals including anthocyanins, phenolics, flavonoids, and organic acids. The present study was designed to analyze the therapeutic potential of dried fig and extract for their potential against hyperglycemia and related complication in the diabetic rat model. Diabetes was induced by using alloxan monohydrate and divided into five groups including Negative-, Positive-, standard drug- group, treated-I (given extract), and treated-II (given 10% dried figs). Fig extract was administered through the intragastric tube, and fig paste was mixed in the feed of the experimental group, and then rats were decapitated after 6 weeks to collect the blood and serum. At the end of the study, biochemical analysis such as fasting blood glucose (FBG), serum glucose, and insulin was performed. Histopathological study of the pancreas showed cell deformation in the positive control group whereas damage was reversed in treated groups. The pancreas was also saved for gene expression analysis. The results revealed that the positive control group has lower expression of INS-1, INS-2, Pdx-1, amylin, and GLUT-2 genes. Results revealed that serum glucose and FBG started to normalize after the administration of treatment (Glibenclamide, dry fig, and fig fruit extract), and insulin concentration also started to improve. 10% dried fig was more effective to control hyperglycemic conditions, which might be due to the presence of fiber. However, the gene expression was more modulated in the group treated with fig extract. The findings of current research suggested the utilization of fig and fig-based products because of their potential to reverse the damage induced by the alloxan or stressors of daily life.

Rare Coexistence of SLC6A9 and TOR1A Gene Mutations in a Neonate Presenting with Hereditary Hyperekplexia and Arthrogryposis Multiplex Congenita

Background: Neonatal hyperekplexia is a rare nonepileptiform disorder characterized by an exaggerated startle reflex associated with generalized hypertonia. We report a newborn with mutation in the glycinergic inhibition pathway resulting in hyperekplexia, associated with features of arthrogryposis multiplex congenita. Clinical Description: A 3-day-old newborn born at term vaginally cried immediately after birth and presented with lethargy, poor cry, and abnormal clonic movements of all four limbs. On examination, there was hyperreflexia and hypertonia in all four limbs along with dislocation of the right knee joint. Blood investigations, including tandem mass spectrometry, serum ammonia, serum, and cerebrospinal fluid glycine levels, were normal, ruling out inborn errors of metabolism responsible for hyperekplexia and arthrogryposis. The magnetic resonance imaging (MRI) brain and electroencephalogram were normal, while the MRI spine showed kyphosis. The genetic evaluation showed heterozygous missense mutation in exon 6 of the SLC6A9 gene and homozygous mutation in the TOR1A gene, which explained the hyperekplexia and the arthrogryposis multiplex congenita. Management and Outcome: The patient received supportive care. Oral clonazepam and levetiracetam were started in view of hypertonia and clonic spasms. Feeding was given by intragastric tube as he had poor suck–swallow coordination. Conclusions: This case highlights an interesting and extremely rare combination of hereditary hyperekplexia and arthrogryposis multiplex congenita existing together in the same patient, confirmed by the corroborating genetic mutations. Awareness of such conditions among pediatricians is essential to order appropriate genetic evaluations and treatment accordingly.

Effect evaluation of supramolecular complex of ivermectin Aniverm-2.0% on postnatal development of rat offspring

The purpose of the research is to detect long-term effects of repeated oral administration of supramolecular complex of ivermectin Aniverm-2.0% on the postnatal development of rat offspring.Materials and methods. The studies were conducted on 16 white pregnant rats that were divided into two experimental and one control groups. The animals were kept under standard conditions of keeping and feeding. The supramolecular complex of ivermectin Aniverm-2.0% was administered to pregnant female rats (n = 6) of group 1 in the form of a suspension using an intragastric tube daily for 7 days at a dose of 15 mg/kg, and group 2 was given the substance of ivermectin (n = 5) at a dose of 8.25 mg/kg. The control female rats (n = 5) were administered 1 mL of distilled water during the experiment. The experimental pregnant females were left until delivery, and then, the development of their offspring was monitored for 45 days. After rat pups were born, the following were recorded: pregnancy duration, litter size, dynamics of weight gain in the rat pups for 21 days, postnatal death during the first 30 days, the ratio of males and females in the litter, periods of eye opening, incisor eruption, detachment of the auricle, appearance of hair coat, descent of testicles, and opening of the vagina. Then we assessed the maturation rate of sensory-motor reflexes in the offspring obtained from the experimental and control groups, the emotional motor behavior and ability for fine coordination of movements in the offspring, and conducted the open field-2 test on day 45 after birth.Results and discussion. No negative effect was detected for supramolecular complex of ivermectin Aniverm-2.0% on the parameters of physiological development of the offspring of the experimental rats within 45 days after birth. The dynamics of their mass, developmental parameters, and formation of motor reflexes during the feeding period remained within the normal values. Developmental indicators of sensory motor reflexes in the control and experimental rat pups had no statistically significant differences.

The synbiotic mixture of Bacillus licheniformis and Saccharomyces cerevisiae extract aggravates dextran sulfate sodium induced colitis in rats

BackgroundUncertain effects of probiotics and/or prebiotics have been reported in experimental and clinical colitis. This study aims to examine the effects of a synbiotic combination comprising Bacillus licheniformis DSM 17236 and Saccharomyces cerevisiae cell wall extract on dextran sulfate sodium (DSS)-induced colitis in Sprague Dawley rats.MethodsAcute colitis was induced in rats by oral administration of DSS 3.5% for 7 days. Fifty rats were divided equally into five groups; one control group and the other groups were induced with colitis and treated with or without the tested synbiotic, mixed with diet, for 28 days and sulfasalazine (100 mg/kg) via intragastric tube once daily for 14 days.ResultsSymptomatically, the synbiotic administration raised the disease activity index (DAI) to comparable scores of the DSS group, specially from the 2nd to 7th days post DSS intoxication. It also induced a significant (p < 0.05) amplification of WBCs, myeloperoxidase (MPO), malondialdehyde (MDA), nuclear factor kappa B (NF-kB) expression and proinflammatory cytokines tumor necrosis factor alpha (TNFα), interferon gamma (INFγ), and interleukin-1 beta (IL-1β) while depressed the antioxidant enzymes glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) when compared with the DSS and control groups. The DSS intoxicated and Synbiotic+DSS groups showed desquamations of the covering epithelium, noticeable diffuse leukocytic infiltrations, sever catarrhal enteritis, ischemic colitis with diffuse coagulative necrosis of the entire colonic mucosa. Contrarily, sulfasalazine proved to be effective in the reduction of the tested inflammatory markers and the pathological degenerative changes of the DSS ulcerative colitis.ConclusionThe examined synbiotic did not ameliorate but aggravated the DSS-induced colitis, so it should be subjected to intensive experimental and clinical testing before their use in animals and human.

ACUTE TOXICITY STUDY BASED ON TOLTRAZURIL, TINIDAZOLE AND LEVAMISOLA

As a result of the studies, it was found that the proposed drug based on toltrazuril, tinidazole and levamisole hydrochloride according to the average lethal oral dose in accordance with GOST 12.1.007–76 belongs to the fourth hazard class - low-hazard substances. To assess the acute toxicity of the drug, experimental and control groups of whites were formed. Wistar rats weighing 190.2±5.92 grams. To study the acute toxicity of the drug based on toltrazuril, tinidazole and levamisole hydrochloride, a suspension was prepared using the Polysorbate 80 emulsifier. The prepared suspension in different dosages was administered through an intragastric tube to experimental animals and an equal volume of physiological saline was administered to the control group of white rats. With the introduction of a drug based on toltrazuril, tinidazole and levamisole hydrochloride at a dose of 3745 mg/kg, the death of two rats was recorded, which is 20% of the experimental group No. 5. With the introduction of the drug at a dose of 5350 mg/kg, 5 dead animals or 50% of experimental group No. 8 were registered, and with the introduction of 6420 mg/kg - 10 dead laboratory animals, i.e. all animals of the experimental group No. 10. When registering the body weight of white rats of the experimental and control groups, no statistically significant differences were found in the indicators for the entire observation period. At the same time, it should be noted that in the groups of experimental laboratory animals in which the drug was tested at a dose of 3745 mg/kg to 5885 mg/kg, lower values of body weight gain were established in comparison with the control. The minimum tolerated dose was found to be 3210.0 mg/kg, LD16 - 3679.7 mg/kg, LD50 - 5029.0 mg/kg, LD84 - 6121.5 mg/kg, LD100 - 6420.0 mg/kg and SLD50 - ±406. The data obtained allow us to proceed to the study of subchronic toxicity and irritant action of the developed drug.

Effect of aloe vera on lipid and sugar levels in male rats exposed to high doses of dexamethasone therapy

The present study was undertaken to observe the effect of the aqueous leaf extract of Aloe vera gel of the reduction in blood glucose and lipid level in hyperglycemia and hyperlipidemia rats. Twenty four male rats were divided into four groups (6 rats/group) and treated as follows for 28 days.G 1 were intubated orally distal water serving as control while, G2 were administrating of Dexamethason -induced diabetic 1 mg/kg/bw. Intraperitoneally, G3 were administrating of diabetic rats given Dexamethason 1mg/kg/bw. + Aloe vera leaf gel extract (300 mg/kg) using an intragastric tube, G4) were administrating of diabetic rats given Dexamethasone 1 mg/kg/bw. intraperitoneally + Aloe vera leaf gel extract (500 mg/kg) using an intragastric tube, the following criteria were measured sugar levels and blood lipid profile. The findings show that Aloe Vera had a significant decrease influence in serum glucose, cholesterol, TG, and VLDL and a significant decrease HDL. In conclusion, this study mention a new evidence of the role of Aloe Vera on the decreasing glucose, lipid profile.

Effect of aloe vera on antioxidant in male rats exposed to high doses of dexamethasone therapy, and histological on liver and pancreas

The present study was undertaken to observe the effect of the aqueous leaf extract of Aloe vera gel of the Antioxidant and histological on liver and pancreas. Twenty_four male rats were divided into four groups (6rats/group) and treated as follows for 28 days.G 1 were intubated orally distal water serving as control while, G2 were administrating of Dexamethason -induced diabetic 1 mg/kg/bw. Intraperitoneally, G3 were administrating of diabetic rats given Dexamethason 1mg/kg/bw. + Aloe vera leaf gel extract (300 mg/kg) using an intragastric tube, G4)were administrating of diabetic rats given Dexamethasone 1mg/kg/bw. intraperitoneally + Aloe vera leaf gel extract (500 mg/kg) using an intragastric tube, the following criteria were measuredAntioxidant and histological on liver and pancreas. The findings show that Aloe Vera had a significant decrease influence in serumAntioxidant (MDA, ACE, and HSP70). In conclusion, this study mentioned a new evidence of the role of Aloe Vera on the decreasing of antioxidant.

Comparison of Two Different Threshold Values for the Measurement of Gastric Residual Volume on Enteral Nutrition Support in the Neurocritically Ill Patients.

BackgroundAlthough recommendations on gastric residual volume (GRV) have been applied to the clinical practice of patients who are intubated, evidence-based data about the GRV of patients who are neurocritically ill are still lacking. We conducted this study to investigate the safety of increased GRV in patients who are neurocritically ill on enteral nutrition (EN) support.MethodsPatients who are neurocritically ill feeding through intragastric enteral tubes were recruited consecutively between July 2018 and June 2021. Patients were divided into a control group (GRV 100 ml) and a study group (GRV 200 ml). Demographic data, admission diagnosis, and severity scores were collected from the patient medical records. The frequency of diet volume ratio (diet received/diet prescribed), the incidence of gastrointestinal complications, and outcome variables were evaluated.ResultsThere were 344 patients enrolled, of whom 197 had mechanical ventilation support. High GRV events in the control group were more frequent than those in the study group (38.1 vs. 22.8%, p = 0.002). The total gastrointestinal complication rate did not differ significantly between the two groups (study group: 61.1%, 102/167 vs. control group: 67.9%, 114/168). In the study group, two patients had aspiration (1.2 vs. 0%, p = 0.245). The study group showed a superior diet volume ratio, but the difference was not significant. The outcomes of the study group were slightly better than those of the control group; however, no significant differences were observed between the two groups concerning the length of stay in the neurointensive care unit (19.5 days vs. 25.3 days) and mortality (10.8 vs. 14.9%) at discharge.ConclusionOur results suggest that 200 ml may be a safe normal limit for GRV in patients who are neurocritically ill.

Acute and subchronic toxicity of multicomponent antiparasitic drugs Insaсar Total C Plus, Insaсar Total K Plus

The purpose of the research is to study acute oral toxicity in mice, and acute dermal and subchronic toxicity in rats of multicomponent antiparasitic Insacar Total C Plus (for dogs) and Insacar Total K Plus (for cats).Materials and methods. The toxicity of the drugs was studied in September-April 2020–2021 at the premises of the VNIIP – FSC VIEV Vivarium. To determine acute oral toxicity, 80 outbred mice weighing 20 g were used, of which 7 test and one control group were formed. The drugs were administered once in a 1 : 3 dilution with polyethylene glycol as a solution through an intragastric tube and an automatic controller. The control animals were intact. After a single administration, the physical condition of the test mice was monitored within 14 days; weight gain, expected clinical toxicity symptoms and possible death were assessed. Before and on days 1, 3, 7, 11 and 14 of the experiment, the test and control mice’s weight gain were evaluated. The toxicity parameters were calculated by the methods of Pershin, Miller and Taintner. In a subchronic experiment, the study drugs were tested on 80 outbred white rats divided into 6 test and 2 control groups. The rats’ coat was also shaved on the back. The solution was applied to the shaved skin area once a day for 7 days at doses of 1,000 mg/kg (0.1 mL/100 g), 500 mg/kg (0.05 mL/100 g) and 200 mg/kg (0.02 mL/100 g) of the animal weight. On day 8 of the experiment, 5 rats from each group were euthanized; their blood samples were taken, and the internal organs were examined. On day 21 of the experiment, the second part of the animals was euthanized to analyze the reversibility of potential pathoanatomical changes after prolonged repeated application of the drug. The results were processed statistically.Results and discussion.The half-lethal dose (LD 50) after oral administration of the drug for dogs to the mice was 2,475 by the Pershin method, and 2,500±388 mg/kg by the Miller and Taintner method. LD50 of the drug for cats when administered into the mice’s stomach was 2,713 by the Pershin method, and 2,650±403 mg/kg by the Miller and Taintner method (hazard class 3). LD 50 when applied to the rats’ skin was more than 10,000 mg/kg (hazard class 4). When applied once to the rats’ skin, the drugs had a slightly irritating effect. In subchronic experiment on the rats with daily drug application on their skin at doses of 1,000 mg/kg, 500 and 200 mg/kg, no negative effects on the general condition or death of the animals were observed during the entire study. Hematological and biochemical parameters of the test rats that were treated with the drug for dogs at a dose of 200 mg/kg, an increased content of lymphocytes up to 83.40% was observed on day 8 of the experiment, and up to 74.20 % in the control; and an increased glucose level up to 6.08±1.23 mmol/L, and up to 4.82±0.70 mmol/L in the control; LDH was up to 766.00±264.19 U/L, and up to 434.80±525.89 U/L in the control.

EVALUATION OF IN VIVO ANTI-DIABETIC ACTIVITY OF ROOT OF CRATAEVA MAGNA LOUR., ON STREPTOZOTOCIN-INDUCED DIABETIC RATS

Objective: The purpose of the study is to evaluate the anti-diabetic effect of the ethanolic extract of root of Crataeva magna Lour., on streptozotocin-induced diabetic rats. Methods: Streptozotocin (45 mg/kg) was used to induce the diabetes mellitus in rats. Afterward, the diabetic rats will be divided into four groups Group I rats served as diabetic control rats, Group II rats were induced diabetes and treated with standard drug through oral intragastric tube, Group III and Group IV were treated with ethanolic extract (200 and 400 mg/kg). Glibenclamide as reference was to evaluate the effect of the extract. Results: The administration of extract decreased the fasting blood glucose and body weight as well as increased level of total cholesterol and triglycerides which and decreased and HDL level. SGPT and SGOT level were significantly reduced in treatment group. Blood urea and creatinine were a significant difference in blood urea and creatinine. Conclusion: The extract of C.magna Lour. exhibited significant anti-diabetic activity evident from blood glucose level, body weight, serum cholesterol profile, SGOT, SGPT, serum creatinine, and serum urea level.

ACUTE ORAL TOXICITY PARAMETERS OF THE COMBINED ANTIPARASITIC DRUG IN THE FORM OF SPRAY

The purpose of the research was to study acute oral toxicity parameters of the combined veterinary Fipronil-, Pyriproxyfen- and Moxidectin-based drug in the form of spray. The studies were performed in the vivarium on 50 outbred white male mice weighing 17–20 g and on 30 outbred white male rats weighing 185–205 g. The drug for the mice was diluted in PEG-400 in the ratio 1:3 and administered by an intragastric tube; we tested doses of 1025 mg/kg, 3075 mg/kg, 5125 mg/kg and 7175 mg/kg. The drug was administered to the rats without dilution; we tested doses of 1640 mg/kg, 3690 mg/kg, 5740 mg/kg and 7380 mg/kg. The animals’ physiological state, intoxication symptoms and possible death were monitored within 14 days. As a result of the studies, toxic effects of the drug were determined and calculated using the Miller-Tainter method. The LD50 of the drug was 4100.0±560.3 mg/kg for mice, and 4458±690.5 mg/kg for rats, on the basis of which it was found that the drug was classified as moderately hazardous substance (hazard category 3 substance) according to GOST 12.1.007-76.

Silymarin from Milk Thistle Fruits Counteracts Selected Pathological Changes in the Lenses of Type 1 Diabetic Rats.

Diabetes is a metabolic disease affecting many tissues and organs. The main etiological factor for diabetic complications is hyperglycemia and subsequent pathologies, such as oxidative stress. One of the organs susceptible to the development of diabetic complications is the eye with all of its elements, including the lens. The aim of this study was to evaluate the effect of silymarin, an extract obtained from milk thistle fruit husks, on the oxidative stress markers in the lenses of type 1 diabetic rats. The study was performed on male rats in which type 1 diabetes was induced with 60 mg/kg streptozotocin injection. Diabetic animals were treated via an intragastric tube with silymarin at 50 and 100 mg/kg doses for four weeks. Multiple oxidative stress and polyol pathway-related parameters were measured in the lenses, and auxiliary biochemical tests in the serum were conducted. Diabetes induced severe pathological changes both in the lenses and the serum, and silymarin counteracted several of them. Nevertheless, the qualitative analyses encompassing all tested parameters indicate that silymarin slightly improved the overall state of diabetic animals. Upon the obtained results, it can be concluded that silymarin reveals a faint positive effect on the lenses in type 1 diabetic rats.

ANTI-DIABETIC POTENTIAL OF HYPHAENE THEBAICA FRUIT IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

Complications of Diabetes mellitus caused by persistent hyperglycemia is a challenge in management of the disease as synthetic drugs used are often expensive, specific and associated with side effects. This study was aimed to determine the anti-diabetic potential of mesocarp extract of Hyphaene thebaica fruit in streptozotocin-induced Diabetic rats. The hypoglycemic effects of methanol, aqueous and ethylacetate extract of Hyphaene thebaica fruit oral glucose tolerance test (OGTT) were determined followed by the effects of the ethylacetate extract on body weight, blood glucose, liver and kidney. Glucose was fed to rats the 30 minutes after pretreatment with extract, followed by measurement of blood glucose levels at 0, 30, 60, 90, 120, and 240 minutes to assess the effect of the extracts on blood glucose levels of the glucose loaded animals. The rats were also divided into six groups and treated ethylacetate extract daily by intragastric tube for four weeks. The result revealed the ethylacetate extract was more hypoglycemic in OGTT than the other extracts. There was a significant (p &lt; 0.05) improvement in body weight of rats administered ethylacetate extract at 400 mg and 200 mg/kg body weight with significant (p &lt; 0.05) decrease in blood glucose, AST, GGT, creatinine, and urea levels. Conclusively, H. thebaica can be used in the management of diabetes evident to its hypoglycemic effects and significant improvement in weight and hepato-renal function.