Death Of Animals Research Articles

Caffeic acid phenethyl ester derivative exerts remarkable anti-hepatocellular carcinoma effect, non-inferior to sorafenib, in vivo analysis

Caffeic acid phenethyl ester (CAPE) and its derivatives exhibit considerable effects against hepatocellular carcinoma (HCC), with unquestioned safety. Here we investigated CAPE derivative 1ʹ (CAPE 1ʹ) monotherapy to HCC, compared with sorafenib. HCC Bel-7402 cells were treated with CAPE 1ʹ, the IC50 was detected using CCK-8 analysis, and acute toxicity testing (5 g/kg) was performed to evaluate safety. In vivo, tumor growth after CAPE 1ʹ treatment was evaluated using an subcutaneous tumor xenograft model. Five groups were examined, with group 1 given vehicle solution, groups 2, 3, and 4 given CAPE 1ʹ (20, 50, and 100 mg/kg/day, respectively), and group 5 given sorafenib (30 mg/kg/day). Tumor volume growth and tumor volume-to-weight ratio were calculated and statistically analyzed. An estimated IC50 was 5.6 µM. Acute toxicity tests revealed no animal death or visible adverse effects with dosage up to 5 g/kg. Compared to negative controls, CAPE 1ʹ treatment led to significantly slower increases of tumor volume and tumor volume-to-weight. CAPE 1ʹ and sorafenib exerted similar inhibitory effects on HCC tumors. CAPE 1ʹ was non-inferior to sorafenib for HCC treatment, both in vitro and in vivo. It has great potential as a promising drug for HCC, based on effectiveness and safety profile.

SISTEM PAKAR DIAGNOSA PENYAKIT SAPI

In the livestock industry, the health of cattle is crucial because diseases can lead to a decrease in production, animal deaths, and economic losses. The high incidence of these diseases is due to ignorance and lack of knowledge about them. Therefore, an expert system was developed to diagnose diseases in cattle. The method used in creating this expert system is forward chaining using the PHP programming language and MySQL database. The result of this research is an expert system application for diagnosing diseases in cattle using forward chaining method, which can be accessed by the public, especially farmers and traders, to identify diseases in cattle, with the hope of improving the efficiency of diagnosis. This system can speed up the disease detection process, minimize human errors, and enable faster and more accurate decision-making by combining artificial intelligence with web technology.

Studying the toxicity and safety of the carbon mass of hemosorbent

In recent years, methods of extracorporeal detoxification using carbon materials have received due recognition and widespread development. Carbon materials for blood detoxification based on coal have firmly taken a dominant position among sorption materials. This is due, first of all, to the fact that carbon sorbents have wide possibilities for selecting the required physicochemical and structural sorption characteristics. It has been established that a single oral administration of biomass to rats at a dose of 75 mg/kg does not cause any signs of intoxication. At the same time, no animal deaths were recorded throughout the entire observation period. There were no gender differences in the sensitivity of rats to the action of the drug. Due to the lack of mortality in the dose range studied, the lethal doses of LD100 and LD50 could not be determined.

Editorial: Programmed cell death in aquatic animals

Editorial: Programmed cell death in aquatic animals

Clustered Regularly Interspaced Short Palindromic Repeat-1 (CRISPR-1) Locus as a Tool for Tracing the Zoonotic History of Salmonella enterica Strains.

Background Salmonella enterica is a significant foodborne pathogen that causes considerable illness and death in humans and animals. The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein (Cas) system in bacteria acts as an adaptive immune defense against invasive genetic elements by incorporating short intergenic spacers (IGSs) into CRISPR loci. These loci serve as molecular records of past interactions with phages and plasmids, providing insights into the transmission and evolution of bacterial strains across different hosts. Aim This study aimed to investigate the diversity of IGSs in the CRISPR-1 locus of S. enterica isolates from humans and camels. The objective was to assess the potential of IGSs to distinguish strains, track sources, and understand patterns of zoonotic transmission. Materials and methods Genomic DNA was extracted from multiple strains of S. enterica, and the CRISPR-1 locus was polymerase chain reaction (PCR) amplified and sequenced. The sequences were compared to identify distinct patterns of IGSs and potential host-specific characteristics. Sanger sequencing and bioinformatics tools were used to classify the IGSs and determine their similarity to known sequences in the National Center for Biotechnology Information (NCBI) database. Results Sequence analysis revealed five distinct CRISPR-1 types among S. enterica isolates from humans and three among camel isolates. The presence of shared IGSs between human and camel S. entericaisolates suggested zoonotic or reverse-zoonotic transmission events. Additionally, host-specific unknown IGSs (UIGS) were identified. Importantly, camel isolates initially identified as S. enterica subspeciesenterica serovar Enteritidis based on rrnH gene sequencing were reclassified as S. enterica serovar Enteritidis based on CRISPR-1 profiling, demonstrating the higher resolution of CRISPR-based genotyping. Conclusion The diversity of IGSs in the CRISPR-1 locus effectively differentiated S. enterica strains and provided insights into their evolutionary origins and transmission dynamics. CRISPR-based genotyping proves to be a promising tool to complement traditional serotyping methods, enhancing the molecular epidemiology of salmonellosis and potentially leading to better management and control strategies for this pathogen.

Acute Toxicity Test of Mulberry Leaf Extract (Morus rubra L) as a Basic Ingredient of Candida Albicans Antifungal on Rattus Norvecigus

Previous research on the effectiveness of mulberry leaves in the growth of candida albicans showed that C. albicans is inhibited in vitro. Mulberry leaf extract is used as a basic ingredient for treatment. In addition to being tested for effectiveness, testing is needed to ensure the level of acute toxicity in experimental animals in determining toxicity levels. The study aimed to test the acute toxicity of mulberry leaf extract on Rattus Norvecigus media in determining the level of toxicity before becoming the basic ingredient of VVC antifungal. The research method uses an experimental laboratory post-test-only control group design with a 9 Rattus Norvegicus media. The average dose is not lethal using LD50 values. Research analysis using ANOVA is One Way to determine the difference in the average weight change of experimental animals. The study's results did not show any deaths of experimental animals or toxic symptoms in administering mulberry leaf extract doses of 0 mg, 100mg, 1000 mg, 1600mg, 2900mg, 5000mg. LD50 value more than 8g/kg BW, included in the non-toxic category (5-15 g/kg BW). The ANOVA statistical test showed a P-value of 0.781 more than a P-value of 0.05, that is, there was no difference in the average change in body weight in the experimental animal group given different treatment doses in each group. The research concludes that mulberry leaf extract does not show a lethal dose of acute toxicity, so it is safe to use as a basic ingredient in treatment sourced from natural ingredients.

Pigs as Models to Test Cardiovascular Devices.

Pigs as laboratory animals are used in preclinical studies aimed at developing medical devices for cardiac surgery. The anatomy of the cardiovascular system of these animals has been well studied and acknowledged as suitable for use and the testing of new cardiovascular devices developed for humans. However, there are no morphometric characteristics of the aortic root and thoraco-abdominal part of porcine aorta. This can lead to difficulties in experimental surgery and even result in the death of experimental animals due to the mismatch in the size of the implantable devices. Thus, such information is essential to enhance the efficiency of surgical technologies used for eliminating aortic pathologies in their various sections. The purpose of our research is to study the anatomy of the aorta in mini pigs and to assess whether the size, age, and sex of the animals affect the size of the main structures in their aortas. In addition, we attempted to compare the results obtained by transesophageal echocardiography (TEE) and angiography. We studied 28 laboratory mini pigs, dividing them into three groups by body weight (40-70 kg, 71-90 kg, and 90 kg). We did not find any relationship between the external somatometric characteristics of the animals and the size of their aortas. Animals have individual anatomical variability in their cardiovascular systems, which means that they need to be examined in terms of preoperative planning by any available method-echocardiography, angiography, or multispiral computed tomography (CT).

A Case of Severe Abomasal Sand Impaction in a Farmed White-Tailed Deer (Odocoileus virginianus) in Florida.

The University of Florida's Cervidae Health Research Initiative (CHeRI) conducted a post-mortem examination of a two-year-old white-tailed doe deceased at a northern Florida white-tailed deer farm. The carcass of the deer had notable emaciation and bloating. Upon opening of the carcass, there was pneumonia and the rumen was tympanic and enlarged. Additionally, the abomasum was distended and contained approximately 5 kg of sand. It is not uncommon for white-tailed deer to engage in geophagia (eating soil or sand), which typically does not result in diseases or fatalities. However, in this animal, we suspect a chronic process that created a physical barrier, hindering nutrient absorption and resulting in physical irritation of the abomasal mucosa with subsequent inflammation. This may have caused a disturbance in immune system function, allowing opportunistic bacteria to colonize and invade other organs, such as the lungs, contributing to the animal's death.

Protective Effects of Iraqi Propolis on Carbimazole-Induced Reduction of Sex Hormones in Female Adult Rats

Background:: Propolis (PR) is used as a health supplement and is widely used in foods and drinks in many parts of the world. This study aimed to know the possible reproductive toxicity effect of the antithyroid drug carbimazole (CZ) in adult female albino rats and to evaluate the possible protective role of Iraqi PR. Methods:: Twenty-four adult female albino rats were randomized into four groups: control, PR, CZ, and PR + CZ. Rats were orally treated for six weeks. Ovarian biochemical and histopathological analyses were performed. Results:: No change in appearance, no signs of toxicity, and no deaths of animals were reported throughout the study period. There was a significant body weight increase only in the PR group. The CZ group displayed a reduction in serum T3 and T4 levels and a rise in serum TSH levels compared to the control. Also, there was a significant decrease in serum T3, T4, and TSH levels after exposure to PR+ CZ compared to control. Exposure to 0.01mg/g body weight of CZ for six weeks results in a significant reduction of serum LH, FSH, and estradiol (E2) in female rats. At the same time, PR alone or with CZ was found to have no significant effect. Biochemical results were consistent with histopathological results. Conclusion:: Iraqi PR provides a protective effect against the reduction of serum sex hormones induced by CZ. Further studies are required to confirm this effect. PR has no effect on CZ activity in reducing thyroxin levels; however, PR might reduce the effects of CZ on TSH levels. Furthermore, PR alone demonstrated an elevation in the weight gain of animals compared to the control group.

Phosphorylation of caspase-8 by RSKs via organ-constrained effects controls the sensitivity to TNF-induced death

Caspase-8 (Casp8) serves as an initiator of apoptosis or a suppressor of necroptosis in context-dependent manner. Members of the p90 RSK family can phosphorylate caspase-8 at threonine-265 (T265), which can inactivate caspase-8 for bypassing caspase-8-mediated blockade of necroptosis and can also decrease caspase-8 level by promoting its degradation. Mutating T265 in caspase-8 to alanine (A) in mice blocked TNF-induced necroptotic cecum damage but resulted in unexpectedly massive injury in the small intestine. Here, we show RSK1, RSK2, and RSK3 redundantly function in caspase-8 phosphorylation, and the duodenum is the most severely affected part of the small intestine when T265 phosphorylation of caspase-8 was prevented. Eliminating caspase-8 phosphorylation resulted in a duodenum-specific increase in basal caspase-8 protein level, which shall be responsible for the increased sensitivity to TNF-induced damage. Apoptosis of intestinal epithelial cells (IECs) was predominant in the duodenum of TNF-treated Rsk1−/−Rsk2−/−Rsk3−/− and Casp8T265A/T265A mice, though necroptosis was also observed. The heightened duodenal injury amplified systemic inflammatory responses, as evidenced by the contribution of hematopoietic cells to the sensitization of TNF-induced animal death. Further analysis revealed that hematopoietic and non-hematopoietic cells contributed differentially to cytokine production in response to the increased cell death. Collectively, RSKs emerges as a previously overlooked regulator that, via tissue/organ-constrained inactivating caspase-8 and/or downregulating caspase-8 protein level, controls the sensitivity to TNF-induced organ injury and animal death.

SPIKENET: An Evidence-Based Therapy for Long COVID.

The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple SARS-CoV-2 variants were reported globally, and a wide range of symptoms existed. Individuals who contract COVID-19 continue to suffer for a long time, known as long COVID or post-acute sequelae of COVID-19 (PASC). While COVID-19 vaccines were widely deployed, both unvaccinated and vaccinated individuals experienced long-term complications. To date, there are no treatments to eradicate long COVID. We recently conceived a new approach to treat COVID in which a 15-amino-acid synthetic peptide (SPIKENET, SPK) is targeted to the ACE2 receptor binding domain of SARS-CoV-2, which prevents the virus from attaching to the host. We also found that SPK precludes the binding of spike glycoproteins with the receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) of a coronavirus, murine hepatitis virus-1 (MHV-1), and with all SARS-CoV-2 variants. Further, SPK reversed the development of severe inflammation, oxidative stress, tissue edema, and animal death post-MHV-1 infection in mice. SPK also protects against multiple organ damage in acute and long-term post-MHV-1 infection. Our findings collectively suggest a potential therapeutic benefit of SPK for treating COVID-19.

Analysis of the parasitological situation regarding eimeriosis in cattle in the Russian Federation

The purpose of the study is to review the spread of bovine eimeriosis in the territory of the Russian Federation. Objectives of the study: to analyze the epizootic situation of bovine eimeriosis in the territory of the Russian Federation. Bovine coccidiosis is widespread in many regions of Russia and in other countries of the world. The pathogens are more than 10 species of eimeria, which have a specific localization in the body of animals, as well as morphological differences from each other. Three species (E. zuernii, E. bovis and E. alabamensis) are characterized by the highest pathogenicity and are most often associated with the clinical manifestation of the disease. Mostly young animals aged from 2 weeks to 1 year are ill, and adult animals have an asymptomatic form of invasion. In many animals, eimeria causes dangerous diseases, accompanied by a decrease in productivity, the birth of weak offspring, often the death of young animals, and additional feed costs per unit of production. In livestock complexes, the incidence of calves with eimeriosis is 10–100%, and mortality is 25–60%. The maximum infection of calves and adult animals is observed in the spring and autumn periods, and in some regions in the autumn-winter period. It was found that with an increase in the density of calves in the machine, their infection with eimeria increases significantly. The invasion of calves was minimal when kept in individual machines. Given that parasites have a complex developmental biology, one of the most importantmeasures in the complex of measures ensuring the prevention and elimination of animal diseases with coccidiosis is currently still pharmacotherapy and prevention, contributing not only to the liberation of animals from parasites, but also to prevent the dispersion of the invasive origin in the environment and to prevent the threat of new infection.

Quercetin isolated from Hedysarum neglectum Ledeb. as a preventer of metabolic diseases

Diseases associated with metabolic disorders seem to affect more and more people worldwide. Biologically active supplements may prevent or relieve metabolic disorders. Quercetin is known for its potential to inhibit metabolic syndrome. This paper introduces an in vivo experiment on rodents. It featured hypoglycemic, hypocholesterolemic, and hepatotoxic properties of quercetin. Quercetin was obtained from the hairy root extract of Hedysarum neglectum Ledeb. Two doses (50 and 100 mg/kg) were used to evaluate its hypoglycemic potential. Rats with induced diabetes were tested for body weight, glucose, and cholesterol while mice with induced hypercholesterolemia were checked for blood cholesterol changes. Potential biochemical and pathological changes in the liver were also studied on rats. Quercetin treatment caused neither significant health problems nor death in the model animals. It had no effect on body weight, even in the animals with induced diabetes. In addition, quercetin did not increase glucose and cholesterol in the blood and triggered no pathological changes in the liver. Quercetin isolated from H. neglectum hairy root extract demonstrated no hepatotoxicity. Unfortunately, it showed no beneficial effect on cholesterol and glucose levels and had no efficacy against metabolic syndrome. Further research is needed to assess the effect of quercetin on other metabolic markers, e.g., genes associated with the metabolism of lipids, carbohydrates, etc.

Playful rehearsals of animal subjugation: The naturalization of animal labour in videogames

In videogames, players commonly encounter virtual animals who perform labour for human benefit. Animal labour is not only physical, but increasingly involves labours of bonding and love which invest the player in the animal's liveliness alongside their utility. This article analyses Stardew Valley, interrogating the ways in which the player encounters and builds relationships with labouring virtual animals. It argues that, through these player-animal relationships, the player rehearses orientations towards animal life which take for granted their subjugation. In Stardew Valley, animals express love in ways which not only obscure their subjugated position, relative to humans, in relationships of domination, but also encourage the player to reproduce those relationships on an expanding scale. This is a naturalization of animal subjugation which, in part, justifies real practices of industrial animal agriculture which lead not only to constant cycles of mass animal death, but also contribute to climate disaster.

Potential Impact of Climate Change-Induced Alterations on Pyroptotic Cell Death in Animal Cells: A Review.

Climate change-induced alterations in temperature variation, ozone exposure, water salinity and acidification, and hypoxia might influence immunity and thus survival in diverse groups ofanimals from fish to mammals. Pyroptosis is a type of lytic pro-inflammatory programmed cell death, which participates in the innate immune response, and is involved in multiple diseases characterized by inflammation and cell death, mostly studied in human cells. Diverse extrinsic factors can induce pyroptosis, leading to the extracellular release of pro-inflammatory moleculessuch as IL-18. Climate change-related factors, either directly or indirectly, can also promote animal cell death via different regulated mechanisms, impacting organismal fitness. However, pyroptosis has been relatively less studied in this context compared to another cell death process, apoptosis. This review covers previous research pointing to the potential impact of climate change, through various abiotic stressors, on pyroptotic cell death in different animal cells in various contexts. It was proposed that temperature, ozone exposure, watersalinity, wateracidification and hypoxia have the potential to induce pyroptotic cell death in animal cells and promote inflammation, and that these pyroptotic events should be better understood to be able to mitigate the adverse effects of climate change on animal physiology and health. This is of high importance considering the increasing frequency, intensity and duration of climate-based changes in these environmental parameters, and the critical function of pyroptosis in immune responses of animals and in their predisposition to multiple diseasesincluding cancer. Furthermore, the need for further mechanistic studies showing the more direct impact of climate change-induced environmental alterations on pyroptotic cell death in animals at the organismal level was highlighted. A complete picture of the association between climate change and pyroptosis in animals will be also highly valuable in terms of ecological and clinical applications, and it requires an interdisciplinary approach. SIGNIFICANCE: Climate change-induced alterations might influence animal physiology. Pyroptosis is a form of cell death with pro-inflammatory characteristics. Previous research suggests that temperature variation, ozone exposure, water salinity and acidification, and hypoxia might have the potential to contribute to pyroptotic cell death in certain cell types and contexts. Climate change-induced pyroptotic cell death should be better understood to be able to mitigate the adverse effects of climate change on animal health.

Infections of reproductive organs in female rabbits

Symptomatic infertility is a temporary or permanent disturbance in reproductive function wherein the animal cannot become pregnant due to diseases of genital organs or systemic diseases. Since female rabbits, due to their precociousness and fertility, are often used for reproduction, the leading causes of symptomatic infertility in them are the absence of estrous cycles or their deficiency and inflammation of tissues of the reproductive system. Infertility is observed in female rabbits developing such infectious diseases as pasteurellosis, spirochetosis, and myxomatosis. It is due to these diseases that obstetric and gynecological pathology (vulvitis, vulvovaginitis, metritis, pyometra, mastitis), long-term infertility, and death of animals are recorded most often. External genitalia (vulva) and mammary glands are the main routes of infection in female rabbits. The most common microorganisms causing inflammatory processes in reproductive organs are non-specific, such as Staphylococcus and Pasteurella, and specific microbes, such as toxoplasma. Spirochetes, Listeria, and Salmonella are much less common. It has been found that on farms of different forms of ownership in the Dnipropetrovsk region, the most common infectious diseases in rabbits are myxomatosis (20 %), viral hemorrhagic disease (13 %), eimeriosis (30 %), pasarulosis (10 %), and spirochetosis (10 %). Inflammation of genital tissues, especially inflammatory processes in the uterus, is the most common disease in female rabbits. The general frequency of uterine diseases increases with age, reaching more than 50% in aged female rabbits. Endometritis was the most frequent inflammatory process diagnosed in 10 % of cases and was potentially purulent, catarrhal, lymphoplasmacytic, or enterohemorrhagic. Metritis was observed in 5 % of cases and pyometra in 3 %. Autopsy of forcibly slaughtered or dead animals revealed such uterine diseases as hydrometer and mucometer. Hydrometers and mucometers comprised 8 % of uterine diseases, and the average age of sick female rabbits was 3 years. The etiology remains unclear but is potentially related to endometrial hyperplasia or endometritis. However, in some cases, no underlying uterine disease was found. During acute infection of the organs of the reproductive system of female rabbits, a serous mucocatarrhal or mucopurulent exudate is released from the genital slit. Chronic inflammatory processes of the genital organs often occur without signs of disease or are manifested by decreased fertility or abortion.

Evaluation of Neoplasia, Treatments, and Survival in Lizard Species.

Neoplasia has been reported in lizards, but more research is needed to accurately document the prevalence and prognosis of the various known neoplasms that affect lizards. This study reviewed medical records from an online database, the Exotic Species Cancer Research Alliance (ESCRA), and reviewed published literature to determine the prevalence of neoplasia, malignancy, metastasis, treatment strategies, and outcomes by species and sex. Records from 55 individual lizards, 20 different species, and 37 different tumors were identified. In the literature, 219 lizards, 59 species, and 86 unique tumors were identified from 72 published case reports. Potential signalment factors such as age, sex, and species were evaluated to see if they affected case outcome. Additional factors including neoplasia type, presence of metastasis, and types of pursued treatments were also evaluated. Statistical analysis was performed to determine whether a factor was significantly associated with animal death due to the identified neoplasia or with animal survival or death due to other causes (non-neoplastic outcomes). Komodo dragons and savannah monitors were more likely to die from neoplasia compared to other lizard species. Cases where the status of metastasis was unknown were significantly associated with death due to neoplasia. Having an unknown status of male versus female was significantly associated with non-neoplastic outcomes of death. Leukemia and islet cell carcinoma were significantly associated with death due to neoplastic causes. Chondrosarcoma, myxosarcoma, osteosarcoma, and squamous cell carcinoma were significantly associated with non-neoplastic outcomes of death. Surgery alone and radiation therapy alone each were significantly associated with non-neoplastic outcomes of death, while lizards not receiving treatment were significantly associated with death due to neoplasia. Benign neoplasia was significantly associated with non-neoplastic outcomes of death. These results will aid in the improved diagnosis and management of neoplasia in lizard species, as well as expanding our understanding of prognostic indicators of neoplasia in lizards.

Median lethal dose (LD50) estimation of Cypermethrin and Profenofos in Swiss Albino mice (Mus musculus)

Present study was undertaken to determine the Oral median lethal dose (LD50) of Cypermethrin, a pyrethroid and Profenofos, an organophosphate pesticide in male and female Swiss albino mice. The selected doses of Cypermethrin based on the pilot study were 200, 225, 250, 275 and 300 mg/kg B.W. for male and 350, 375, 400, 425 and 450 mg/kg B.W for female animals. Corresponding doses of Profenofos based on the pilot study was found to be 10, 15, 20, 25 and 30 mg/kg B.W for male and 20, 25, 30, 35 and 40mg/kg B.W for female. Pesticide was dissolved in corn oil and administered orally to different groups of male and female mice, consisting of 10 animals in each group. Possible death of animals was monitored up to 96 h to calculate the median lethal dose (LD50) of CYP and PFF. The results obtained in this study suggest that oral LD50 of the CYP and PFF dissolved in corn oil was found to be (249.06 ±30.75, 406.38 ± 64.28)and (24.26 ±6.43, 39.67 ±6.2) mg/kg B.W. respectively in male and female Swiss albino mice.

Pharmacological evaluation of anti-inflammatory, antipyretic, analgesic, and antioxidant activities of Castanopsis costata leaf fractions (water, ethyl acetate, and n-hexane fractions): the potential medicinal plants from North Sumatra, Indonesia.

Inflammation, fever, and pain can be associated with several diseases, and the synthetic drugs used in the treatment of these conditions often have severe side effects. As a result, there is a need for effective, economical, and safe alternative drugs, such as those derived from medicinal plants. Therefore, this study aimed to evaluate the anti-inflammatory, antipyretic, analgesic, and antioxidant activities of Castanopsis costata leaf fractions (CcLF), as well as its acute toxicity. For anti-inflammatory, antipyretic, and analgesic tests, rats were given CcLF (WFCC, EAFcC, and n-HFCC) at 50 and 100 mg/kg, diclofenac sodium (10 mg/kg), paracetamol (150 mg/kg), aspirin (100 mg/kg), and tramadol (20 mg/kg). For the antioxidant activity test, various concentrations of CcLF were used ranging from 25 to 200 μg/mL. This study also looked into whether there could be any acute toxicity and histopathology of the liver, stomach, and kidneys in experimental animals. The administration of CcLF significantly inhibited the increase in foot edema volume, and CcLF (EAFCC at 100 mg/kg) considerably decreased rectal temperature and was proportional to the standard drug paracetamol, and significantly inhibited pain sensation in various models. Additionally, CcLF showed strong antioxidant activity, and its administration at a dose limit of 5000 mg/kg/day did not show any toxic effects or death in test animals. The results of the current confirmed that CcLF has demonstrated anti-inflammatory, antipyretic, analgesic, and antioxidant properties in experimental models, and is practically non-toxic.

Acute heat trauma model in rats, gender-dependent thermoresistance, and screening of potential thermoprotectors

Heat trauma (HT) is an urgent medical and social problem. Heat damage is a widespread effect of the environment on humans, driven by global warming, military conflicts, technological disasters, work in hot environments, and engagement in extreme sports and tourism. The aim of the study: to propose a model of acute HT in rats that does not cause the death of animals, to determine the dependence of thermoresistance on gender, and to compare the effectiveness of the thermoprotective effects of a range of non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, and glucosamine hydrochloride in this model. Materials and Methods: The experiment was conducted on adult white rats of both genders. Acute HT was modelled by using a specially developed method involving heat exposure to animals at +55 °C for 30 minutes, followed by a recovery period of 60 minutes. Rectal temperature was measured every 15 minutes. The degree of hyperthermia in males and females was determined. The presence and intensity of the thermoprotective effect of glucosamine hydrochloride (G h/ch), diclofenac sodium, acetylsalicylic acid (ASA), nimesulide, etoricoxib, celecoxib, and paracetamol were evaluated through intragastric administration 60 minutes before heat exposure. The results were analyzed using the STATISTICA 12.0 program. Results: It was established that heat exposure at +55 °C for 30 minutes effectively replicates acute HT in rats without causing animal fatalities, adhering to bioethical requirements. Body temperature increases by 10-13 %, characterized as a heat stroke. Occasionally, thermoresistant animals are encountered, where the temperature increase during the first 15 minutes of exposure is less than 1 °C. These animals should not be used for further modelling of heat trauma. Male rats are more sensitive to the effect of high environmental temperatures than females, exhibiting greater hyperthermia (temperature increase of 5.03±0.39°C compared to 3.72±0.22 °C in females, p<0.01). The thermoprotective effect of glucosamine hydrochloride depends on gender, being more pronounced in males. Among the 6 tested COX inhibitors, the most significant thermoprotective effect was observed in the highly selective COX-2 inhibitor celecoxib and the weakly selective central inhibitor paracetamol, warranting in-depth research into their impact on organ and system states following heat trauma, as well as the mechanisms of their thermoprotective action. The thermoprotective effect is not associated with selectivity towards COX (cyclooxygenase): it is not observed in the highly selective COX-2 inhibitor etoricoxib and moderately selective COX-2 inhibitor nimesulide, as well as in non-selective COX inhibitors such as diclofenac sodium and aspirin, which also slows down the recovery of body temperature after heat exposure. Conclusions: A convenient and simple model of acute HT in rats is proposed, demonstrating higher thermosensitivity and a more pronounced thermoprotective effect of glucosamine hydrochloride in males. A significant thermoprotective effect was identified in celecoxib and paracetamol, surpassing other investigated NSAIDs. The mechanism and specific features of this effect require further clarification