White Male Rats Research Articles

IMPACT OF NF-κB AND NRF2 TRANSCRIPTION FACTOR MODULATORS ON METABOLIC CHARACTERISTICS IN MANDIBLE BONES OF RATS DURING RECOVERY FROM INCOMPLETE FRACTURE UNDER CHRONIC ALCOHOL INTOXICATION

This study aims at investigating the influence of specific modulators of NF-κB and Nrf2 transcription factors on oxidative-nitrosative stress indicators and bone biopolymer depolymerization in mandibular bone following incomplete fracture under chronic alcohol intoxication (CAI). Twenty-eight white male Wistar rats were divided into five groups: Group 1 comprised "falsely injured" rats, while Group 2 underwent incomplete mandibular fracture (IMF) under CAI exposure. Rats in groups 3 and 4 received intraperitoneal injections of ammonium pyrrolidinium dithiocarbamate, an inhibitor of NF-κB activation, in a dose of 76 mg/kg, and dimethyl fumarate, an Nrf2 inducer, in a dose of 15 mg/kg three times a week for 14 days following the modeling of IMF under CAI exposure. The activity of total NO synthase, including its constitutive and inducible isoforms, along with ornithine decarboxylase, and concentrations of peroxynitrites of alkaline and alkaline-earth metals, free hydroxyproline, N-acetylneuraminic, and hexuronic acids were assessed in the homogenate of the standard mandible area using a spectrophotometric method. The findings have demonstrated that the administration of ammonium pyrrolidine dithiocarbamate and dimethyl fumarate notably decreased the activity of NO synthase (primarily its inducible isoform) and the concentration of peroxynitrite in the mandibular bone homogenate, while increasing the activity of ornithine decarboxylase, a key enzyme in polyamine biosynthesis. Furthermore, under experimental conditions, the use of ammonium pyrrolidine dithiocarbamate and dimethyl fumarate limited the depolymerization of bone biopolymers (collagen, glycoproteins, and proteoglycans), thereby facilitating effective reparative osteogenesis.

THE INFLUENCE OF QUERCETIN ON THE PRODUCTION OF REACTIVE OXYGEN-NITROGEN FORMS IN THE STRUCTURE OF THE INTERSTITIAL SPACE OF RAT TESTICLES WITH LONG-TERM EFFECT OF TRIPTORELIN

Quercetin is a flavonoid commonly found in fruits, vegetables, and seeds. Flavonoids can help prevent cardiovascular diseases, reduce the risk of degenerative brain processes and cancer. Studies have shown that blocking the synthesis of luteinising hormone can lead to oxidative stress in the liver, heart, and salivary glands of rats. The purpose of this study was to assess alterations in the interstitial space of rat testes, identify sources of nitric oxide production, and measure the intensity of oxidative stress in the testes during long-term experimental central blocking of luteinising hormone synthesis by tryptorelin. The study was conducted on 15 sexually mature male white rats. The animals were divided into two groups. The first group (control) received a subcutaneous injection of 0.9% sodium chloride solution. The second group (experimental) received a subcutaneous injection of tryptorelin at a dose of 0.3 mg/kg of active ingredient for 365 days, with simultaneous addition of quercetin to the diet, which was administered orally through a gastric tube three times a day. Total nitric oxide production was assessed by measuring the activity of total NO synthase (gNOS). The activity of gNOS was determined by the increase in nitrite (NO2-) after incubation in Tris-buffered saline. The nitrite concentration was determined using the Gris-Ilosvay reagent at a wavelength of 540 nm. The activity of the inducible (iNOS) and constitutive (cNOS) isoforms was also determined using a selective iNOS inhibitor, aminoguanidine hydrochloride. The production of superoxide anion radical (O2--) was measured by the increase in the formation of diformazan resulting from the reaction of O2-- with nitroblue tetrazolium after incubation in a buffered solution containing sodium hydroxide. The administration of quercetin mitigates the adverse effects of tryptorelin on the structural and functional components of the connective tissue in the rat testes. This effect is observed on day 365 and is characterised by fibrosis and impaired nitric oxide production by constitutive isoforms of NO synthase.

Camel milk or silymarin could improve the negative effects that experimentally produced by aflatoxin B1 on rat’s male reproductive system

BackgroundCamel milk and silymarin have many different beneficial effects on several animal species. Meanwhile, Aflatoxins are mycotoxins with extraordinary potency that pose major health risks to several animal species. Additionally, it has been documented that aflatoxins harm the reproductive systems of a variety of domestic animals. The present design aimed to investigate the impact of aflatoxin B1 (AFB1) on rat body weight and reproductive organs and the ameliorative effects of camel milk and silymarin through measured serum testosterone, testes pathology, and gene expression of tumor necrosis factor (TNF-α), luteinizing hormone receptor (LHR), and steroidogenic acute regulatory protein (StAR) in the testes. A total of sixty mature male Wister white rats, each weighing an average of 83.67 ± 0.21 g, were used. There were six groups created from the rats. Each division had ten rats. The groups were the control (without any treatment), CM (1 ml of camel milk/kg body weight orally), S (20 mg silymarin/kg b. wt. suspension, orally), A (1.4 mg aflatoxin/kg diet), ACM (aflatoxin plus camel milk), and AS (aflatoxin plus silymarin).ResultsThe results indicated the positive effects of camel milk and silymarin on growth, reproductive organs, and gene expression of TNF-α, LHR, and StAR with normal testicular architecture. Also, the negative effect of AFB1 on the rat’s body weight and reproductive organs, as indicated by low body weight and testosterone concentration, was confirmed by the results of histopathology and gene expression. However, these negative effects were ameliorated by the ingestion of camel milk and silymarin.ConclusionIn conclusion, camel milk and silymarin could mitigate the negative effect of AFB1 on rat body weight and reproductive organs.

Effect of quercetin administration on electron microscopic changes in testicular interstitial endocrinocytes during long-term central blockade of luteinising hormone in rats

Quercetin is a flavonoid with potential health benefits and it may help prevent cardiovascular diseases, reduce the risk of degenerative brain processes and cancer, and has antioxidant properties that neutralise free radicals. Substances in this group also have antioxidant properties, which help the body protect itself from the harmful effects of free radicals by neutralising these unstable molecules. Research indicates that the impact of free radicals on cell structure is associated with the development of chronic diseases such as diabetes, cancer, and cardiovascular pathologies. The aim of the study was to investigate the effect of quercetin administration on electron microscopic changes in the interstitial endocrinocytes of the testes under long-term central blockade of the synthesis of luteinising hormone by tryptorelin. The experiment involved 35 sexually mature male white rats. They were divided into two groups: the control group (I) received saline, while group II received subcutaneous injections of tryptorelin at a dose of 0.3 mg of active ingredient per kg of rat body weight to induce experimental central deprivation of luteinising hormone synthesis and additionally, quercetin was administered three times a day by gastric tube in terms of body weight. The study has demonstrated that the administration of tryptorelin results in structural and functional changes in the connective tissue components of rat testes. Specifically, there are quantitative and qualitative disorders in the population of interstitial endocrine cells, as well as electron microscopic changes at the subcellular level. Various pathological changes and abnormalities in the functional activity of the internal components of the cell were detected on days 270 and 365 of the experiment. The frequency, number, and size of Reinke crystals in relation to the cell volume correlated with changes in cells and increased at later stages of the study. A similar correlation with testosterone levels has not been found in the literature, which leads us to classify Reinke crystals as the result of degenerative processes in the cell. Thus, additional administration of quercetin reduces the adverse effect of tryptorelin and delays the onset of changes in the structure of interstitial endocrinocytes from day 180 to later observation periods.

Histopathological changes in the spleen of rats exposed to N,N-dimethylhydrazine with the following protective input of Au/Ag/Fe

Colon cancer is one of the leading causes of cancer-related deaths worldwide. Despite the growing number of studies on nanoparticles of different metals, there is still a lack of reliable information about their ability to work together as a composition and their antitumor effects. It has been established that the regulation of genes encoding proteins of the Bcl-2 family changes in cancer. Bcl-2 family proteins can be a potential target in cancer diagnosis and have a prognostic value in treating cancer with chemotherapeutic drugs. The tumor microenvironment includes myeloid suppressor cells, tumor-associated neutrophils, and tumor-associated macrophages that promote cancer progression and are derived from splenic hematopoietic stem cells and progenitor cells. The work aimed to ascertain histological changes and expression of Bcl-2 family proteins in the spleen of rats with N,N-dimethylhydrazine-induced carcinogenesis followed by the protective administration of Au/Ag/Fe nanometal composition. The study was conducted on 72 outbred white male rats. Colon adenocarcinoma was modelled by N,N-dimethylhydrazine hydrochloride administration for 30 weeks. Animals received an aqueous dispersion of Au/Ag/Fe nanoparticles intragastrically once a day for 21 days at a dose of 0.842 mg Ag/0.0526 mg Fe/1.625 μg Au per 1 kg of rat body weight. Paraffin sections of the spleen were stained with hematoxylin and eosin. For immunohistochemical analysis, sections were stained with rabbit monoclonal antibodies to Bcl-2. Under conditions of 30-week exposure to N,N-dimethylhydrazine hydrochloride, blood circulation disorders, stasis, thrombosis, reduction in the size of white pulp lymphatic nodules and loss of their zonation were histologically proved in the rat's spleen. The development of sclerotic processes in the organ was noted. It was indicated that using metal nanoparticles under N,N-dimethylhydrazine hydrochloride-induced colon carcinogenesis leads to less evidenced morphological manifestations of structural changes in the spleen. Immunohistochemically, the expression of Bcl-2 protein in the white pulp of the spleen of animals subjected to correction was lower than in animals without the corrective effect of the composition of nanoparticle metals. Administration of the Au/Ag/Fe metal nanoparticle composition to intact white rats does not cause pathological changes in the spleen morphology. The structural components of the red and white pulp match the typical histological structure of the organ.

The influence of chronic hyperhomocysteinemia on the structure and immune processes of the spleen in young rats

Homocysteine is a sulfur-containing amino acid that is an intermediate product of methionine metabolism. Entering the body with products of animal origin, methionine undergoes a number of biochemical transformations. Hyperhomocysteinemia has a negative effect on the body, causing damage to all organs and systems and leading to disruption of homeostasis. The study aims to study the characteristics of changes in the structure and immune processes of the spleen of young rats with chronic hyperhomocysteinemia. Experiments were performed on 22 white male rats. The animals were divided into control and experimental groups (11 individuals in each group) during the experiment. Chronic hyperhomocysteinemia was achieved by administering D, L-thiolactone homocysteine hydrochloride to experimental group animals at a dose of 200 mg/kg of body weight intragastrically in a 1 % starch gel solution once a day for eight weeks. After the end of the experimental simulation of chronic hyperhomocysteinemia, the animals were removed from the experiment by anaesthetising by decapitation and using thiopental anaesthesia. Histological preparations were studied using an SEO SСAN light microscope. Experimental modelling of chronic hyperhomocysteinemia in young rats was not accompanied by significant morphological changes in the stroma and red pulp of the spleen. T-cell periarterial sheaths and B-cell nodules in animals from the experimental group underwent changes. B-cell proliferation leads to growth within the white pulp, expansion of the marginal zones, which become more blurred and infiltration of these cells into the red pulp. Evaluation of the red pulp in the spleen of young rats from the experimental group showed a particular expansion in the venous sinuses, which may be a sign of reaction to the influence of homocysteine and slight swelling of these vessels. The number of T-cells in young animals in the periarterial cuffs is slightly reduced, which can be explained by the increasing activity of macrophages. However, T-cells also infiltrated the red pulp. Such penetration of white blood cells into the red pulp is accompanied by the expansion and “washing out” of the marginal zones of lymph nodes. Thus, the increased homocysteine level significantly potentiated proliferation and partially inhibited apoptosis in T-lymphocytes but did not directly affect dormant T-cells.

Structural changes of pancreatic components under the conditions of long-time exposure to opioid in the experiment

Use of narcotic drugs in clinical practice for the purpose of obtaining analgesic and anti-inflammatory effects requires a comprehensive morphological study of the peculiarities of structural arrangement of organs under the conditions of exposure to opioids. The aim of our study was to establish the peculiarities of restructuring of the structural components of the pancreas under the conditions of long-time exposure to opioids in the experiment. The study included 24 adult laboratory white male rats. The test animals were divided into 2 groups, the experimental and control ones. The experimental animals were daily administered narcotic analgesic nalbuphine intramuscularly (once a day in the same interval) for four weeks, and the control animals were administered saline solution. The following research methods were used: bloodstream injection followed by translucence of sections of the pancreas and their photographing, morphometry of the vessels of the pancreatic hemomicrocirculatory bed, histological, histochemical studies and electron microscopy of the pancreas, blood biochemistry test; statistical processing of the study results using a software package. After four weeks of opioid exposure, lesion of the pancreatic parenchyma microstructure was observed, manifested by swelling and infiltration by lymphocytes and macrophages of the pancreatic connective tissue stroma, disorganization of the exo- and endocrine parts of the parenchyma, deep destructive changes in the excretory ducts, as well as in the vessels of the hemo- and lympho-microcirculatory bed of the pancreas. At the ultrastructural level, deep dystrophic changes of exo- and endocrinocytes of the pancreas were identified, in particular, loss of regular shape, karyopyknosis and karyorrhexis of the nuclei, swelling and clearing of cytoplasm, development of microcystic degeneration of cells, loosening and disorganization of the basement membrane, which can result in impairment of exocrine function of the pancreas and complication of the process of secretory granules excretion into the lumen of the intercalated ducts. A significant decrease, compared to the control group, in the diameter of arterioles, density of exchange vessels network, as well as increase in the diameter of venules, the indicator of trophic activity of the tissue, are the evidence of destructive changes in the hemomicrocirculatory bed of the pancreas under the effects of nalbuphine. Significant changes in blood biochemistry parameters (alanine aminotransferase, aspartate aminotransferase) after a four-week administration of nalbuphine are illustrative of the process of pancreatic tissue destruction. Therefore, four-week administration of opioid leads to profound changes in the micro- and ultrastructure of the pancreas, vessels of its hemomicrocirculatory bed, and blood biochemistry parameters in experimental white rats.

Assessment of the Effect of Propolis Extract on Enzymatic Antioxidants and Lipidperoxidation

The current study aimed to evaluate the effect of propolis (aquatic, alcoholic) and vitamin E on the state of experimentally induced oxidative stress status in the male white rats. The animals were distributed into five groups: The first group (negative control) was given only water and food until the end of the study period. The second group (positive control) was dosed with H2O2 through drinking water at a concentration of 0.5% for 21 days. The third group was dosed with H2O2 at a concentration of 0.5% and treated with aqueous extract of propolis at a concentration of 4% for 21 days. The fourth group was dosed with H2O2 with drinking water at a concentration of 0.5% and treated with an alcoholic extract of propolis at a concentration of 1% for 21 days. The fifth group was dosed with H2O2with drinking water at a concentration of 0.5%. It was treated with vitamin E at a concentration of 50 mg/kg for 21 days. The results showed that the treatment with the water and alcoholic extract of propolis and vitamin E has led to a significant increase (p≤0.05) in the concentrations of the antioxidants enzyme (superoxide dismutase, catalase, glutathione peroxidase) and a moral decrease in the Malmondialdehyde compared to the negative control.

Morphofunctional characteristics of the liver and pancreas under the influence of the hepatoprotector “Remaxol” against the background of acute alcohol damage in rats

The goal. To study the effect of hepatoprotective drug “Remaxol” on morphology of the liver and pancreas as well as on blood serum indices in rats with alcohol damage. Materials and Methods. The study was conducted on mature male white laboratory rats divided into three groups: the first (control group) - intact animals, the second and third (experimental groups) - daily part of the rats received 40 % aqueous ethanol solution (96 % ethanol in a dose of 8ml/kg weight) for 7 days, then part of the rats from the experimental group were injected “Remaxol” in a dose 5 mg/kg weight daily for 7 days. Morphological study of the liver and its macrostructure was carried out; diameters of hepatocytes, sinusoid capillaries and pancreatic acini in animals of the control and experimental groups were measured; general and biochemical blood parameters were assessed. Results. Blood tests demonstrated acute alcohol poisoning in experimental groups (leukocytosis); short-term (7 days) alcohol damage had less effect on the size of hepatocytes than on the size of pancreatic acini; pancreatic acini were more reactive on toxic influence of alcohol; in the liver and pancreas there were signs of inflammatory reaction (cell swelling, lymphocytes infiltration). Conclusion. Histological picture of the liver and pancreas of the animals with acute alcohol poisoning on the background of “Remaxol” treatment showed a decrease in the toxic effect of 40 % alcohol on hepatocytes and pancreatocytes, normalization of their morphological parameters.

The effect of EKORMIN on rats with diabetes mellitus model: effectiveness on fasting blood glucose, MDA, and insulin levels

Antioxidant use for additional diabetes mellitus therapy is growing, such as okra (Abelmoschus esculentus) and turmeric (Curcuma longa), which are rich in flavonoids and have beneficial effects on diabetes mellitus. This study aimed to determine the effects of okra turmeric extract (EKORMIN) on Fasting Blood Glucose (FBG), malondialdehyde (MDA), and insulin levels in diabetic rats. The research was conducted from December to January 2022 at PSPG UGM using experimental research with a pre-posttest-controlled group design. White male Wistar rats (n = 35) randomly grouped into five: negative control (STZ-NA), positive control (STZ-NA+metformin 1,8 mg/200 gBW), P1 (STZ-NA+EKORMIN low dose 130,5;110,5 mg/kgBW), P2 (STZ-NA+EKORMIN moderate dose 261;221 mg/kgBW), P3 (STZ-NA+EKORMIN high dose 522;442 mg/kgBW). The intervention lasted 14 days. Data analysis was performed using one-way analysis of variance statistical tests and post hoc follow-up tests. EKORMIN in all doses, EKORMIN reduced FBG and MDA levels and increased insulin levels (p<0,05). P2 and P3 were not significantly different from the metformin (PG) group (p>0,05). The decrease in FBG (-167,05±-2,8 vs -175,86±-1,4 mg/dL) and MDA levels (-6,32±0,33 vs -7,98±0,07 nmol/ml) P3 was higher than P2. Similarly for increased insulin levels (121,47±3,03 and 164,09±4,48 pg/ml). EKORMIN was effective in reducing FBG and MDA levels and increased insulin levels in diabetic rats. EKORMIN has antidiabetic effects and has potential for type 2 diabetes mellitus treatment.

Psychomodulatory and anxiolytic effects of ACTH(4-7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro against the background of experimental model of thyroid hyperfunction

The experimental study is devoted to the identification of possible psychomodulatory and anxiolytic effects of ACTH(4- 7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro under conditions of thyroid hyperfunction. Material and methods. The experiment was performed on white male rats, which were divided into groups: I – control; II – rats with hyperthyroidism model, III and IV – animals receiving ACTH(4-7)-Pro-Gly-Pro (Semax) and ACTH(6-9)-Pro-Gly-Pro at doses of 174 and 178 μg/kg/day, respectively, for 21 days against the background of hyperthyroidism. The development of experimental hyperthyroidism in animals was induced by administration of an aqueous solution of potassium iodide at a dose of 75 µg/kg by intragastric gavage, daily for 3 weeks. Behavioural activity was assessed using psychopharmacological tests “Lattice” and “Light-Dark box” in standard modification. Results and discussion. Under conditions of experimental hyperthyroidism in the “Lattice” test, changes in psychomotor behaviour of animals were observed in the form of suppression of orienteering and exploratory activity, namely, a decrease in the number of stands and exploratory “peeks” downwards. In the test “Light-Dark box” against the background of thyroid hyperfunction, an increase in the level of anxiety was observed, manifested in a decrease in the time spent in the light compartment, the number of transitions between compartments and racks, as well as an increase in the number of assessments of “risk” – “looking out” of the compartment. The studied substances ACTH(4-7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro in conditions of experimental hyperthyroidism promoted the correction of the above-mentioned behavioural disorders, eliminating the anxiety-depressive state of laboratory animals. Conclusions. When studying the effect of ACTH(4-7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro substances under conditions of experimental hyperthyroidism on behavioural activity of white rats in the tests “Lattice” and “Light-Dark box” it was revealed that the studied peptide compounds exhibit psychomodulatory and anxiolytic effects, correcting behavioural reactions.

Potential Benefits of Ethanol extract of Anredera cordifolia for Antiobesity of High Fat diet-Induced Obesity in White Male Rat Wistar

تستمر الوفيات المرتبطة بالسمنة في الارتفاع ، لذلك من الضروري إنقاص الوزن لتجنب المضاعفات ، نريديرا كورديفوليا هو نوع من النباتات النضرة من الجنس، باسيللسيا يستخدم على نطاق واسع في طب الأعشاب لتقليل وزن الجسم. تهدف الدراسة الحالية إلى تقييم الفوائد المحتملة لمستخلص الإيثانول من نريديرا كورديفوليا لنماذج الفئران السمنة لتقليل الوزن الناجم عن نظام غذائي عالي الدهون. من خلال تجريب مع اختبارات ما بعد فقد تم تصميم مجموعة ضابطة مع نموذج سمنة 36 جرذًا ، مقسمة إلى مجموعتين: ثلاث مجموعات تحكم (K1 ، K2 ، K3) وثلاث مجموعات معالجة (K1 ، K3 ، K4) (P1 ، P2 ، P3) ، أعطيت جميع مجموعات تحتوي على نسبة عالية من الدهون باستثناء K1 نظام غذائي قياسي ، K2 بدون علاج ، و K3 مع أورليستات. تلقت مجموعة العلاج من مستخلص الإيثانول نريديرا كورديفوليا بجرعات مختلفة ، P1 50 مجم / كجم من وزن الجسم ، P2 100 مجم / كجم من وزن الجسم، و P3 150 مجم / كجم من وزن الجسم. بعد 4 أسابيع من العلاج، قُتلت جميع مجموعات الفئران ، وتم قياس مستويات ERK و PPARγ في الأنسجة الدهنية الحشوية في البطن باستخدام ELISA والكيمياء المناعية. يتم قياس وزن الجسم ومحيط البطن أثناء فحص القياسات، وقد لوحظ فقدان الوزن عند تناول مستخلص الإيثانول نريديرا كورديفوليا بجرعات 100 و 150 مجم / كجم من وزن الجسم، مع انخفاض مستويات ERK و PPAR . يستخدم مستخلص الإيثانول من نريديرا كورديفوليا كمضاد للسمنة. تقلل آلية فقدان الوزن هذه من عامل نسخ PPARγ وتقلل من مستويات ERK بحيث تقل عملية تكوين الدهون.

Comparative analysis of the integration of autologous and allogeneic cryopreserved tendons in the femoral canal on a model of laboratory animals

Allogeneic tendon grafts are seriously demand in knee joint plastic surgery. The novel method of tendon cryopreservation, including sterilization with supercritical carbon dioxide, was developed in N.V. Sklifosovsky Research Institute for Emergency Cryopreserved tendons retain their normal fiber structure without significant loss of mechanical properties. At the next stage it was necessary to evaluate cryopreserved tendons′ integration inside bone canal in experimental animals.The aim of study. To evaluate morphologic changes of autologous and allogeneic tendons inside the femur in rats and to determine the effect of tendon transplantation on the physical activity.Material and methods. The study was conducted on white inbreed male rats. Three groups of animals were formed: the control group (animals without tendon transplantation), the 1st experimental group – animals with autologous tendon transplantation, the 2nd experimental group – animals with allogeneic tendon transplantation. In animals of the experimental groups the through channel was formed in the distal metaepiphysis of the femur and a tail tendon graft 0.5 x 0.1 cm was placed there. To assess the physical activity of the animals, we studied maximum distance that the animals could run 3 and 6 weeks after transplantation was determined, using treadmill test. The graft structure was evaluated on histological preparations in transmitted light, stained with hematoxylin-eosin and Van Gieson′s stain. To assess the preservation of collagen fibers we checked the autofluorescence intensity of collagen.Results. According to the treadmill test, the distance run by the animals of both experimental groups did not significantly differ from the values in the control group. Histological analysis after 3 weeks in both experimental groups revealed signs of fibers′ decomposition in the absence of inflammatory infiltration and maintaining close contact with bone trabeculae. The autofluorescence intensity of the collagen fibers in grafts corresponded to normal or was close to normal. After 6 weeks, the animals of both experimental groups revealed areas of graft fusion with their own bone, Sharpe fibers were actively formed. In both groups, numerous small vessels with diameters up to 10 microns were detected in the area of tendon-bone contact. Infiltration of grafts by inflammatory cells was absent or very insignificant, active migration of fibroblasts to the tendon area was also not observed. In both groups, tendon grafts had areas where fiber decompactization was observed. In the area of contact with the bone, the autofluorescence of tendon fibers was sharply increased, which indicates the chemical cleavage of collagen. At 3 and 6 weeks after transplantation the effect of fixation (integration) of the tendon with bone tissue was observed in both experimental groups.Conclusions. Allogeneic tendon grafts did not cause a pronounced inflammatory or immune reaction in experimental animals. 6 weeks after transplantation of autologous and allogeneic tendons, the integration of grafts inside the femoral canal was observed. Cryopreserved allogeneic tendons were able to integrate into the body's own tissues without pronounced structural and functional disorders. According to the treadmill test, the distance covered by the animals of both experimental groups did not differ statistically significantly from the values in the control group (without tendon transplantation) after 3 and 6 weeks

The Effect of Sapodilla Leaf Extract on IL-6 and TGF- β Levels of Skin Tissue (Experimental Study on Male White Rats of Wistar Strain Exposed to UV Light)

Excessive exposure to ultraviolet light affects cell and tissue homeostasis which has a damaging effect on DNA characterized by the formation of reactive oxygen species (ROS). Inflammation due to UV rays is the main cause of oxidative stress in the skin. Healing of wounds caused by sunburn through a complex process consisting of inflammatory cell infiltration, cell proliferation, and tissue remodeling phases to restore normal skin integrity and function, rapid healing and epithelialization to prevent infection and minimize functional and aesthetic complications. The researchers aimed to see the effect of administering sapodilla leaf extract cream (Manilkara zapota) on IL-6 and TGF-β levels in Wistar rats with sunburn. Experimental study with a post test only control group design using a total of 30 mice as experimental animals, divided randomly into 4 treatment groups consisting of a control group, a placebo group, a sapodilla leaf cream group with a dose of 25% and a 50% cream group. Mouse skin tissue exposed to UV was analyzed using the ELISA method to determine the levels of IL-6 and TGF-β. There was no significant difference in the average IL-6 levels between treatment groups with the one way anova difference test, a p value of 0.25 (p0.05), there was a significant difference in the average TGF-β levels for each group with a p value of 0.005 (P0.05), Manilkara zapota leaf extract cream had a significant effect on TGF-β levels at a dose of 50%. Administration of Manilkara zapota leaf extract cream has a dose-dependent effect on IL-6 and TGF-β levels in skin tissue of mice exposed to UV.

The Effect of Sapodilla Leaf Extract (Manilkara Zapota L.P Royen) on IL-1 and TNF- α Expression in Male White Rats Wistar Strain Induced with UVB Light

Excessive UVB exposure causes health problems in humans, the effect on the skin is molecular and cellular changes. Sunburn is the most obvious acute clinical effect, resulting in the production of TNF-α by keratinocytes, IL-1 is a cytokine that influences TNF-α. Skin wounds release various damage associated molecular patterns (DAMPs) which will activate inflammatory signaling pathways such as NLRP3 inflammasomes and toll-like receptors (TLRs) which cause increased production of inflammatory cytokines. The aim of this study was to examine the anti-inflammatory effect of Manilkara zapota leaf extract which was assessed based on the expression of IL-1 and TNF-α in Wistar rats exposed to UVB. Post-test only control group design experimental research using rats (Rattus norvegicus) as research objects, divided into 4 groups, namely (K1) control rats without treatment, (K2) rats exposed to UVB light then given placebo cream, (K3) rat group exposed to UVB light then given 25% sapodilla leaf extract cream, and (K4) mice were exposed to UVB light then given 50% sapodilla leaf extract cream. The average expression of IL-1 using the One-Way ANOVA test was 0.197 (p0.05), which means there was no significant difference in the average expression of IL-1 between groups. Meanwhile, the average TNF-α expression between groups was 0.036 (p0.05), the results showed that there was a significant difference in the average TNF-α expression between groups, TNF-α expression using the Post Hoc LSD test of sapodilla leaf extract cream 50% dose (K4) reduced TNF-α expression to a lesser extent than K1 or K2. Administration of leaf extract cream (Manilkara zapota) affected the expression of TNF-α, but did not affect the expression of IL-1 in a mouse model experiencing sunburn.

Oral Safety Evaluation of the Aqueous Fruit Extract of Annona Muricata in Wistar Rats

Annona muricata fruit (i.e. Soursoup or custard apple a tropical plant species known for its edible fruit)has been attributed with numerous medicinal benefits (including antimicrobial, anti-inflammatory, anti-protozoan, antioxidant, anxiolytic, anti-stress, anti-ulcerogenic, wound healing, hepato-protective, anti-icteric, hepatoprotective, anticancer and antihyperglycemic activities) as well as some toxicological effects (neurotoxicity and neurodegeneration). Despite its ancestral use and wide applications in human health, scientific information on its oral safety remains scanty. In this study, the oral safety of 100 mg/kd/day, 200 mg/kg/day and 400 mg/kg/day of the aqueous fruit extract of Annona Muricata (AFAM) was evaluated in young adult, male and female white albino Wistar rats using standard acute and 42-days sub-chronic oral toxicity testing guidelines on anthropometric, biochemical, hematological and histo-pathological endpoints. In addition, preliminary qualitative and quantitative analyses of AFAM were undertaken using standard procedures. Results of the study showed that the estimated LD50 value for the acute oral toxicity study of AFAM calculated to be greater than 5 g/kg body weight/oral route although the testing was associated with transient but reversible behavioral toxicities. For its sub-chronic oral toxicity testing, AFAM treatment resulted in profound %weight gain, decreases in the serum triglycerides and very low density lipoprotein cholesterol and liver enzymes. Similarly, prolonged oral AFAM treatments caused significant decrease and increase in the differential neutrophils and platelet counts, respectively while the hist-opathological features of hepatic steatos is and renal tubule collapse in the AFAM-treated livers and kidneys, respectively suggested possible increased intrahepatic lipids biosynthesis and nephrotoxicity. The preliminary phytochemical analyses of AFAM showed the presence and relative amount of flavonoids, alkaloids, tannin, glycosides, saponin, and reducing sugars while the Gas Chromatography-Mass spectroscopy showed the relative abundance of thirteen compounds. Composite analyses conducted on the extract showed the presence of carbohydrate (64.65%), protein (2.14%), moisture content (8.07%), ash value (6.73%), lipid (14.22%) and fiber (4.19%). Overall, the study suggested that the prolonged AFAM oral treatments could predispose to the development of fatty liver disease from de novo intrahepatic biosynthesis of triglycerides, nephrotoxicity and hematotoxicity. In conclusion, the results of this study showed that prolonged consumption of AFAM should be with a great caution as it could pose serious health concerns.

Effect of subchronic use of unsymmetrical dimethylhydrazine on contractile activity of isolated lymphatic vessels

Introduction. Unsymmetric dimethylhydrazine (UDMH, heptyl) is widely used as a rocket fuel. Heptyl belongs to especially dangerous substances (hazard class I). UDMH with chronic intragastric administration has a cardiotropic effect, which served as the basis for studying its effect on the contractile activity of lymphatic vessels, since they are part of the vascular system. In addition, lymphatic vessels are considered as objects similar in terms of parameters of phase contractile activity with the heart and having a certain commonality of regulatory mechanisms of cardiomyocytes and smooth muscle cells of lymphangions.
 Materials and methods. The toxic effect of UDMH was evaluated on a model of isolated rat lymphatic vessels with subchronic intragastric administration of heptyl for 28 days at doses of 0.02; 0.2; and 2 mg/kg.
 Results. The use of UDMH in all studied doses led to a decrease in the contractile activity of lymphatic vessels, which manifested itself in the suppression of the frequency and amplitude of contractions and, as a consequence, the integral indicator – minute productivity. At the same time, the tonic voltage increased dose-dependent. When assessing the state of the endothelium of lymphatic vessels using acetylcholine, a decrease (inversion) of the response of lymphangions to the vasodilator was revealed.
 Limitations of the study. The study was performed on male white rats and does not take into account gender differences in the effect of NDMG on lymphatic vessels. 
 Conclusion. As a result of the study, it was found that UDMH in doses of 0.02; 0.2; and 2 mg/kg causes inhibition of the pumping function of lymphatic vessels, due to a violation of the processes of both excitation and contraction in smooth muscle cells of lymphangions.

Histological changes in the structural components of the gums in lipopolysaccharide periodontitis

Summary. Inflammatory diseases of periodontal tissues are one of the most important problems in dentistry. There is a strong connection between periodontal pathology and inflammatory diseases of the stomach. The aim of the study – to investigate pathomorphological changes in rat periodontal tissues with generalized lipopolysaccharide periodontitis associated with chronic atrophic gastritis. Мaterials and Methods. The experiments were performed on white outbred male rats weighing 160–180 g. 30 animals were used during the work. The tested animals were divided into the following groups: I – intact rats (control); II – animals with a model of generalized lipopolysaccharide periodontitis. For a morphological study of the periodontium, a fragment of the upper jaw was isolated. Histological preparations were studied using an SEOSCAN light microscope. Such classical research methods make it possible to study the structure of tissues, as well as the nature and depth of morphological changes, the sequence of development of destructive and regenerative processes. Results and Discussion. It has been established that with generalized lipopolysaccharide periodontitis, a reorganization of all structural components of the gum tissue occurs. It is manifested by changes in the epithelium of the mucous membrane of the gums, an increase in the stratum corneum, a decrease in the spinous layer, expansion of intercellular spaces, growth of lymphocytic infiltration, swelling of the connective tissue of the mucous membrane, expansion, blood filling of veins and hemocapillaries, cells of the walls of fibrous structures. Conclusions. Concomitant chronic atrophic gastritis significantly aggravates the pathomorphological picture of periodontitis induced in animals by the endotoxin of gram-negative microflora lipopolysaccharide.

The Potential of Ethanol Extract of Temu Kunci (Boesenbergia rotunda (L.) Mansf.) Rhizomes as an Anticonvulsant Against Male White Rats

The temu kunci extract was previously reported to have quite good antioxidant activity. One of the causes of seizures is oxidative stress. There has yet to be much exploration of temu kunci extract as an anticonvulsant. This study examines the anticonvulsant activity of 70% ethanol extract of Boesenbergia rotunda (L.) Mansf. against male white rats. The parameters observed were the onset and duration of HLE (Hind Limb Extension) with a digital electroconvulsiometer with a power of 150 mAmp and 50 hertz for 0.2 seconds. The test group was divided into five treatment groups, namely group 1 to group 3 (K1-K3), with extract doses: 100 mg/kgBW, 200 mg/kgBW, and 400 mg/kgBW, respectively, while K4 was a positive control using valproic acid (Depakote 1.54 mg/kgBW), and normal control group (K5) with Na-CMC 0.5%. The results were analyzed using one-way ANOVA and continued with the Tukey test. From the research carried out, information was obtained that 70% ethanol extract of temu kunci at a dose of 400 mg/kgBB had the best potential as an anticonvulsant in prolonging the onset of HLE (seconds) and shortening the duration of HLE (seconds) in mice comparable to the positive control. Temu kunci has the potential to be further developed as an anticonvulsant drug candidates in the future.

Anxiolytic-like Activity, Antioxidant Properties, and Facilitatory Effects on the Short-Term Memory Retention of Molsidomine in Rats.

Compelling evidence indicates that nitric oxide (NO) exerts a significant influence on the central nervous system, participates in the modulation of neurotransmitter release, contributes to the regulation of cognitive functions, and plays a crucial role in modulating various aspects of neural activity. We aimed to explore the influence of two NO donors, molsidomine (MSD) and V-pyrro/NO, on the innate spontaneous psychomotor abilities and short-term memory in rats. Using an actimeter test, the locomotor activity, stress-sensitive behavior, and anxiety level were investigated. The influence on the animal`s cognitive functions was evaluated usingthe Y-maze test to assess the spontaneous alternation percentage, number of arms visited, number of alternations, and the preference index. Four distinct groups of five white male Wistar rats were exposed to the intraperitoneal treatments as follows: Control batch-0.3 mL/100 g of body weight saline solution, Mg batch-200 mg/kbwof magnesium chloride, MSD batch-1 mg/kbw of molsidomine, and V-pyrro/NO batch-5 mg/kbwof V-pyrro/NO. The intraperitoneal administration of MSD resulted in a significant reduction in spontaneous behavior and exploratory skills but was less pronounced than the positive control drug, magnesium chloride. Conversely, treatment with V-pyrro/NO led to only a slight decrease in horizontal movements during the actimeter test. MSD administration, but not V-pyrro/NO, notably increased the rate of spontaneous alternation in the Y-maze test. Additionally, the use of MSD resulted in an increase in the blood level of brain-derived neurotrophic factor and the intensification of the antioxidant enzymes, superoxide dismutase, and glutathione peroxidase activity. In our experimental setup, we demonstrated that MSD exposure led to a decrease in spontaneous behavior, showed anxiolytic effects and antioxidant activity, and improved spatial memory acquisition in rats.