Postoperative anesthetic complications are not uncommon. Nonetheless, surgical procedures induce specific anatomical and physiological changes. Managing patients undergoing surgery remains complex across various phases of hospital care. Anesthesiologists frequently administer up to half a million doses during their careers, and morbidity and mortality linked to improper dosing and administration postoperatively are frequent concerns. The likelihood of errors is unpredictable and can lead to serious consequences. This review aims to assist anesthesiologists in adopting updated clinical skills to better assess and manage anesthetic complications. The purpose of this literature review is to explore and discuss the main categories of adverse complications and mortality rates following anesthetic administration. The information was gathered through electronic searches, including Google Scholar and PubMed. Anesthesiologists need to classify complications systematically to outline anesthetic risks clearly. Doing so will improve outcomes for vulnerable patients and enable faster, more accurate interventions.
This research focused on comparing the effects of Securinega virosa leaf extract and its partitioned fractions against methicillin-resistant Staphylococcus aureus (MRSA). The extraction process utilized 80% methanol, and the resulting crude extract underwent phytochemical screening using established protocols. Antimicrobial potency of the crude methanol extract and its aqueous and chloroform fractions was assessed using the agar well diffusion method. Additionally, their minimum inhibitory concentrations were determined. The phytochemical analysis revealed that the leaf extract of S. virosa contained various bioactive compounds, including alkaloids, flavonoids, saponins, steroids, tannins, terpenes, cardiac glycosides, anthraquinones, and reducing sugars. When tested for antibacterial activity, the crude extract at concentrations of 100, 50, 25, 12.5, and 6.25 mg/ml produced inhibition zones averaging 14.67 ± 0.82, 10.33 ± 0.82, 8.33 ± 0.41, 6.67 ± 0.41, and 4.33 ± 0.82 mm, respectively. For the partitioned fractions, the aqueous extract yielded inhibition zones of 10.50 ± 0.35, 6.67 ± 1.47, 4.67 ± 0.82, 1.67 ± 2.04, and 1.33 ± 1.63 mm across the same concentrations. The chloroform fraction resulted in inhibition zones of 10.33 ± 1.08, 6.67 ± 0.41, 4.33 ± 1.08, and 2.66 ± 1.78 mm, respectively.Regarding the minimum inhibitory concentration, the crude extract displayed effectiveness starting at 25 mg/ml, while both the aqueous and chloroform fractions showed inhibitory activity at 50 mg/ml. Overall, all forms of S. virosa extracts tested (crude methanol, aqueous, and chloroform) demonstrated activity against MRSA, with the crude extract exhibiting the most pronounced antibacterial effect.
Turmeric (Curcuma longa L.) has antiestrogenic effects that may interfere with the activity of the hypothalamic-pituitary axis, thereby disrupting estrogen production and influencing both uterine weight and diameter. This experiment investigated how turmeric extract affects uterine parameters in female white rats (Rattus norvegicus, Sprague Dawley strain). A total of 28 rats were assigned to four groups: the control group (C) received only H₂O. In contrast, treatment groups T1, T2, and T4 were administered turmeric extract at doses of 250 mg/Kg BW, 500 mg/Kg BW, and 1000 mg/Kg BW, respectively, each combined with 1 ml of H₂O. The treatments were given once daily for five days. Results indicated that turmeric extract at 250 mg/Kg BW and 1000 mg/Kg BW led to a significant reduction in both uterine weight and diameter. In summary, turmeric extract reduced uterine size and weight, indicating its antiestrogenic capability in female rats.
According to the World Health Organization (WHO) estimates, there were 558,000 new cases of rifampicin-resistant tuberculosis, with 82% of these classified as multidrug-resistant tuberculosis (MDR-TB). This study aimed to investigate the outbreak of MDR-TB in River Nile State, Sudan, and identify the risk factors associated with its occurrence. A descriptive cross-sectional hospital-based study was conducted involving two hundred specimens from patients suspected of having MDR-TB, tested using the automated GeneXpert assay. The GeneXpert results indicated that Mycobacterium tuberculosis was detected in 81 cases (40.5%), and among these positive results, 13 (16%) were confirmed as MDR-TB. Furthermore, 7 of the MDR-TB cases had a history of previous treatment, accounting for approximately 53 percent of MDR patients. In contrast, the other 6 MDR-TB cases were new, representing 47% of the MDR-TB patients. In addition, 4 MDR-TB patients had a history of contact with other MDR-TB cases. The prevalence of MDR-TB in River Nile State, Sudan, was found to be 16%, which is higher than the WHO estimate for Sudan at 10.1%. The findings highlighted that prior contact with MDR-TB patients is the primary risk factor for developing MDR-TB, emphasizing that treatment adherence and increased social awareness about MDR-TB transmission are essential preventive measures.
Measuring trace element concentrations in human hair serves as an important analytical method for screening potential deficiencies, excesses, or biochemical imbalances of these microelements in the body. In this research, using an inductively coupled plasma–mass spectrometry (ICP-MS) analyzer, the authors aimed to identify toxic trace elements (Al, Pb, Hg) and quantify key mineral elements (Ca, Mg, Cu, Zn) in healthy individuals with good nutritional status. The study included a sample of 75 adult women aged 30–35 years from various regions across the country. Hair samples weighing 100 mg and measuring 3 cm from the scalp base were collected for trace element analysis and evaluation. Results showed that 12 participants (16%) exhibited elevated intracellular Mg levels (1.2 mmol/L), increased Ca levels (0.72 mmol/L), yet decreased mean Ca/Mg ratios (0.58). Conversely, 6 participants (8%) demonstrated low mean values of Mg (0.004 mmol/L) and Ca (0.04 mmol/L) but had a high Ca/Mg ratio. At the time of analysis, none of the subjects displayed signs of acute or severe heavy metal intoxication. The hair trace element content reflected the environmental and lifestyle factors of the individuals from different regions of the country.
Medications, as essential tools in healthcare, undergo laboratory evaluation before being applied in treatment. Since cellular and organ functions are largely consistent across animals and humans, many processes in animal cells mirror those in human cells. From a biological standpoint, humans are categorized as animals. In experimental pharmacology, animals are utilized to examine disease effects on living tissues, evaluate new treatments, including animal medications, and assist in the training of future health professionals and scientists. They have significantly contributed to research progress, enabling the discovery of various new drugs through animal experimentation. However, animal testing presents specific challenges, including issues related to animal procurement, the complexity of experimental procedures, strict regulatory guidelines, ethical concerns, and, frequently, the perspectives of students. Consequently, modern advancements, such as computer simulations, are increasingly being adopted as substitutes for animal use. This article highlights the role of animals in experimental pharmacology while also acknowledging proposed alternatives for pharmacology education.
This study examines the acute toxicity of Monizen® forte when administered to white male mice through intragastric and subcutaneous routes. The evaluation of acute toxicity parameters for MONIZEN® forte was performed at the pharmacology and toxicology laboratory and vivarium of VNIIVSGE, affiliated with the FGBNU FNC VIEW RAN. The toxicological testing followed the protocol outlined in the “Guidelines for conducting preclinical studies of drugs. Part one” (2012).The median lethal dose (LD50) of MONIZEN® forte was found to be 2524 ± 91.5 mg/kg for subcutaneous injection in white nonlinear mice, whereas the oral (intragastric) administration showed an LD50 of 953.82 ± 156 mg/kg. According to the acute toxicity results in mice after a single intragastric dose, MONIZEN® forte is categorized as a moderately toxic compound under the 3rd hazard class in line with the hygienic classification GOST 12.1.007-76. Administering doses higher than recommended via either oral or parenteral routes caused toxic effects on the liver and kidneys in the tested mice.
This article focuses on examining the structure of microorganisms and their antimicrobial drug resistance during the provision of in-hospital medical care for patients with COVID-19. Among monotypic fungal infections, Candida albicans predominated at 46.82% (n = 375), followed by Candida glabrata at 21.97% (n = 176). Streptococcus pneumoniae accounted for 25.24% (n = 617), while the combined antimicrobial presence of S. pneumoniae with Candida species represented 11.17% (n = 273), ranking highest in isolation frequency among all microorganisms. In deceased patients, the dominant pathogens identified were Klebsiella pneumoniae at 36.3% (n = 159) and Candida fungi at 21.92% (n = 96). Analysis of antimicrobial resistance revealed that S. pneumoniae (n=890) exhibited low resistance rates to benzylpenicillin (4.2%, n = 37), levofloxacin (11.5%, n = 102), and linezolid (0%), but showed elevated resistance to erythromycin (27.4%, n = 244), lincomycin (25.2%, n = 224), and doxycycline (15.5%, n = 141). The vast majority of K. pneumoniae isolates (n = 326) demonstrated resistance to ampicillin (97.9%), cefuroxime (94.2%), cefotaxime (87.7%), ceftazidime (85%), and cefepime (73%), with comparatively lower resistance to amoxicillin-clavulanic acid (52.1%, n = 170) and meropenem (33.4%, n = 109). Microorganisms exhibiting pan-drug resistance accounted for 7.6% (n = 125) of isolates, with the highest proportion of PDR strains attributed to K. pneumoniae, comprising 33.4% (n = 109) of all Klebsiella isolates. C. albicans and S. pneumoniae are the most frequently isolated pathogens among COVID-19 patients receiving inpatient care. The rising detection of extensively drug-resistant (XDR) and pan-drug-resistant (PDR) Klebsiella spp. underscores the critical need for careful selection of empirical antibacterial therapies.
This report presents a case of a potential pharmacokinetic drug-drug interaction (DDI) between fluconazole (FLU) and vancomycin (VCM) in a patient who underwent hepatobiliary surgery and biliary drainage. The patient was receiving treatment with vancomycin, meropenem, and fluconazole for an infectious condition. The exact effects of FLU and VCM on each other’s pharmacokinetics have not been fully explored. However, understanding the role of renal transporters (such as multidrug resistance-associated proteins, organic cation transporters, and P-glycoprotein) in the excretion of these drugs is crucial for predicting drug disposition and optimizing dosage. Inhibiting these transporters is often the underlying mechanism of drug interactions. Pharmacokinetic monitoring showed that when FLU was co-administered with VCM, the trough concentration and half-life of VCM increased unexpectedly compared with when VCM was given alone. These alterations in pharmacokinetic parameters suggest a possible DDI between FLU and VCM. Therefore, caution should be exercised when these drugs are used together, and VCM trough concentrations should be carefully monitored to minimize toxicity risk.
Diabetes mellitus remains one of the most prevalent chronic diseases worldwide and is projected by the World Health Organization to become the seventh leading cause of mortality by 2030. In efforts to enhance therapeutic strategies for diabetes, mineral-based compounds are being explored for their supportive benefits. This study investigates the potential effects of the novel mineral formulation Dibeston on renal excretory function in a model of alloxan-induced diabetes. The experimental design involved 40 white laboratory rats assigned to five groups: Group 1: healthy controls; Group 2: alloxan-induced diabetes (untreated controls); Group 3: alloxan-induced diabetes treated with Dibeston; Group 4: alloxan-induced diabetes treated with Asparkam; and Group 5: alloxan-induced diabetes treated with a selenium-based preparation. Key renal parameters, including blood glucose, serum creatinine, urine output (polyuria), and urinary protein levels (proteinuria), were measured. The findings indicate that Dibeston significantly improves renal function in alloxan-induced diabetic nephropathy, suggesting its potential as an adjunct in diabetes management.
The application of various agricultural pesticides can lead to adverse effects on bodily tissues. This study evaluated the impact of dermal exposure to malathion on sex hormone levels and its potential carcinogenicity in mice. 30 adult male mice were randomly assigned to control and treatment groups. The treatment group received a topical application of malathion at 1 ppm (1 ml) for 12 weeks. After the exposure period, serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were analyzed, and tissue samples were collected post-necropsy. Cytotoxicity was assessed using the micronucleus assay and MTT method in vitro, and the IC50 value was calculated. Results showed no significant difference in LH levels between groups; however, both testosterone and FSH levels declined significantly in the treated mice. Histological evaluation revealed mild liver toxicity in the treatment group. Additionally, the frequency of micronuclei at various Malathion concentrations was significantly elevated compared to controls (P < 0.05). Overall, these findings suggest that dermal exposure to malathion can reduce reproductive hormone levels and induce cytotoxicity in mice.
Doxorubicin, an anthracycline, is a potent anti-cancer drug; however, its clinical use is hindered by its acute and chronic side effects, particularly cardiotoxicity. This study aimed to assess the protective effects of quercetin on doxorubicin-induced cardiotoxicity. Wistar rats were divided into five groups: a control group receiving saline (1 mL/kg), a quercetin control group receiving DMSO (1 mL/kg), a quercetin group receiving quercetin (20 mg/kg), a doxorubicin group receiving doxorubicin (25 mg/kg) intraperitoneally for three days, and a pretreatment group receiving quercetin (20 mg/kg) for 14 days before being treated with doxorubicin (25 mg/kg). After 14 days, the rats’ weights were recorded, and heart tissue samples were collected for histopathological examination. The results revealed significant weight loss in the doxorubicin-treated animals (P < 0.05), while quercetin pretreatment prevented the weight loss. Pathological analysis showed that quercetin protected the heart tissue from doxorubicin-induced damage. Overall, this study suggests that quercetin pretreatment effectively prevents doxorubicin-induced cardiotoxicity, likely due to its antioxidant properties.
Royal jelly, a secretion produced by bees, has been previously shown to have beneficial effects on the nervous system. This study aimed to explore its potential in alleviating anxiety and controlling seizures in mice. To assess its anti-convulsant properties, 25 male mice were divided into 5 groups, with strychnine administered 30 minutes after royal jelly treatment to induce seizures. Key outcomes, including seizure onset and duration and mortality rates, were measured. A separate group of 35 male mice was used to evaluate the anxiolytic effect. Statistical analysis was performed using one-way ANOVA, considering P < 0.05 as significant. The results demonstrated that royal jelly doses of 200 and 400 mg/kg significantly delayed seizure onset and reduced seizure duration compared to the control group. In addition, the mortality rate in these groups was significantly lower than in the control group (P < 0.05). In the anxiety test, royal jelly doses of 50 and 100 mg/kg notably increased the stopping time and the number of entries into the maze arms compared with the control group (P < 0.05). These findings suggest that royal jelly effectively reduces seizures induced by strychnine and has potential anxiolytic effects in mice.
The chemistry of α-(arylhydrazono)-β-ketoaldehydes has attracted significant attention due to their use as intermediates in organic synthesis and as building blocks for biologically active compounds. This study presents the synthesis of a novel series of 3,3'-(5-methyl-1-phenyl-1H-pyrazole-3,4-diyl)bis(2-arylhydrazono-3-oxo-propanal) (3a-i), created through coupling reactions of sodium 3,3'-(5-methyl-1-phenyl-1H-pyrazole-3,4-diyl)bis(3-oxoprop-1-en-1-olate) (2) with arenediazonium chloride. The subsequent condensation of these compounds 3a-i with hydrazine hydrate produced a new series of bis(arylazo)-terpyrazole derivatives (5a-i). The new compounds were characterized using spectroscopic techniques and basic evaluations. Furthermore, the electronic absorption spectra of the compounds were recorded in various buffer solutions, and their acidity constants (pK) were calculated. The study also examined the correlation between these constants and Hammett substituent constants. Results indicated that the compounds predominantly exist in the bis-hydrazo form (5A). Compounds 5a-i were evaluated for their antibacterial and anticancer properties against the HepG2 cell line in vitro.
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is the most severe form of motor neuron degeneration. This study aims to: (1) compare genetic and non-genetic contributors to ALS development, (2) evaluate the pharmacological mechanisms of riluzole and its therapeutic potential across multiple conditions, and (3) explore treatment combinations for managing symptoms throughout ALS progression. The analysis was conducted using data from established electronic medical databases. The most frequently implicated genetic mutations in ALS include SOD1, SETX, FUS, VEGF, VAPB, ANG, TARDBP, FIG4, OPTN, ATXN2, VCP, UBQLN2, SIGMAR1, CHMP2B, PFN1, ERBB4, HNRNPA1, C9orf72, dynactin 1, H46R, and A4V. Additional risk factors include oxidative stress, glutamate-induced excitotoxicity, autoimmune responses, protein misfolding and aggregation, inflammation, and viral infections. Riluzole’s therapeutic actions are attributed to several mechanisms: (1) inhibition of repetitive neuronal firing, (2) blockade of persistent sodium currents in motor neurons, (3) enhancement of calcium-activated potassium currents, (4) reduction of presynaptic neurotransmitter release, and (5) attenuation of postsynaptic receptor responses. Combining riluzole with antioxidants such as vitamins E and C, coenzyme Q10, creatine, and selenium may enhance therapeutic efficacy in ALS. Symptomatic treatments include nonsteroidal anti-inflammatory drugs, opioids for pain relief, and agents like Baclofen and Dantrolene to manage spasticity. Memantine, Nimesulide, and Gabapentin show promise for further research. Due to its diverse mechanisms, riluzole is also being investigated for use in Parkinson’s disease, Huntington’s disease, Machado-Joseph disease, multiple sclerosis, spinal muscular atrophy, and various neuropsychiatric conditions, including anxiety, autism, depression, and schizophrenia.
The Ebola virus is a highly infectious pathogen with no effective antiviral treatments currently available, prompting ongoing research into potential therapeutic options. This study evaluated the inhibitory effects of licensed non-viral drugs on Ebola virus entry and replication using bioinformatic tools. A descriptive-analytical approach was used, in which the chemical structures of selected drugs were first generated in ChemDraw Ultra 10.0 and then energy-optimized in Hyperchem 8.0. Molecular docking was performed using AutoDock4.2 to simulate interactions between the drugs and viral proteins. The analysis revealed that the interactions involved primarily hydrophobic, π-π stacking, hydrogen bonding, and cation-π interactions. Chloroquine, diphenoxylate, and amodiaquine showed the strongest binding affinity, with the most negative docking energies, indicating their potential as effective inhibitors of the GP and VP40 proteins. Conversely, erythromycin and dirithromycin, due to their high hydrophilicity, exhibited weaker binding results. Overall, the study highlighted that drugs with hydrophobic components, effective hydrogen bonding, and tertiary amines tend to show enhanced anti-Ebola properties. The bioinformatic analysis suggests that these drugs could serve as promising candidates for inhibiting Ebola virus entry and replication.
Testicular toxicity is recognized as an underlying factor contributing to male infertility. This study evaluated the protective effects of Artemisia herba-alba against calcium tetrachloride (CCl₄)-induced toxicity in rats, focusing on its impact on ERCC1 gene expression. 20 male Wistar rats were randomly divided into four groups (n = 5 per group). Group I served as the untreated control. Group II received oral CCl₄ (0.4 ml/200g) every other day for three weeks. Group III was administered Artemisia herba-alba (ART) extract orally at 500 mg/kg body weight every other day for three weeks. Group IV was treated with both ART extract (500 mg/kg b.w.) and CCl₄ (0.4 ml/200g) on alternating days over three weeks. Parameters assessed included body weight, relative kidney weight, serum testosterone, tissue oxidative stress markers, ERCC1 gene expression, and testicular histology. The results revealed that CCl₄ exposure led to reduced body weight, lower tissue glutathione (GSH), decreased serum testosterone, elevated lipid peroxidation, upregulated ERCC1 expression, and disrupted testicular histoarchitecture. Conversely, ART co-treatment mitigated these effects, improving testicular histology, downregulating ERCC1 expression, and partially preserving body weight and testosterone levels. Further research with extended treatment periods is recommended to confirm the therapeutic potential of ART in managing testicular toxicity.
Sildenafil citrate (SC), known for its role as a phosphodiesterase type-5 (PDE5) inhibitor, enhances the activity of cyclic guanosine monophosphate (cGMP). This study explores SC’s influence on blood sugar regulation and blood-related parameters in rats with diabetes induced by streptozotocin (STZ). 50 male Wistar rats were randomly assigned to four experimental groups: (i) a control group (n = 10), (ii) a control group receiving SC (n = 10), (iii) a diabetic group (n = 15), and (iv) a diabetic group treated with SC (n = 15). Diabetes was triggered using a single intraperitoneal dose of STZ (50 mg/kg), followed by oral administration of SC at 20 mg/kg daily for six weeks. Blood analyses were conducted to evaluate fasting glucose, insulin, HbA1c, liver enzymes (AST, ALT), renal markers (urea, creatinine), and coagulation profiles (PT, aPTT, fibrinogen, protein C, protein S). Diabetic rats showed significant increases in glucose, HbA1c, AST, ALT, urea, creatinine, and fibrinogen levels, along with reductions in insulin, aPTT, protein C, and protein S compared with non-diabetic controls. PT remained unaffected. SC did not significantly alter any parameters in non-diabetic rats, but in diabetic ones, it restored most measurements toward normal levels (P < 0.05). These findings indicate that SC may support better glycemic control and improve microvascular function, offering potential therapeutic value in mitigating diabetes-related complications.
By the mid-20th century, the growing ineffectiveness of sulfonamides and antibiotics in treating bacterial infections led to the emergence of numerous antibiotic-resistant strains. In response, efforts have focused on developing new chemotherapeutic agents, modifying existing antibiotics, and employing enzyme inhibitors to counteract resistance mechanisms. Neocytin is a multicomponent chemotherapeutic formulation composed of tetracycline, levomycetin, novocaine, and ascorbic acid. This study investigates the physico-chemical properties of Neocytin and assesses its toxicological profile, including acute and chronic toxicity, irritant effects, and impact on mucous membranes. Additionally, its influence on body weight in animal models was evaluated. The findings indicate that Neocytin is a low-toxicity agent for warm-blooded animals, exhibiting mild acute toxicity at a dose of 0.3 ml/kg, and is classified as a Class IV hazardous substance (minor hazard). Long-term administration at doses 3–5 times therapeutic levels did not adversely affect animal health, clinical status, metabolic function, or the integrity of vital organs and tissues.
The global impact of the COVID-19 pandemic continues, driven by the emergence of various SARS-CoV-2 variants and the limited availability of effective therapeutic options. The viral entry process requires the SARS-CoV-2 spike protein to be activated by host cell proteases, particularly TMPRSS2 and CTSL. These proteases facilitate viral membrane fusion and support the endocytic uptake of the virus. In this study, a computational approach using virtual screening was applied to discover compounds that could simultaneously inhibit both TMPRSS2 and CTSL. Two pharmacophore models were constructed from the binding pockets of these proteases, each in complex with its respective ligand. These models were employed to screen a library containing 41,775 compounds, including 10,849 drugs from the ChEMBL database and 30,926 natural products from the NPASS database. This process identified 115 compounds—54 pharmaceutical drugs and 61 natural products—that matched both the TMPRSS2 and CTSL pharmacophore models. The identified compounds were then docked into the protease structures to further refine the list. Molecular docking simulations identified 17 top candidates (5 drugs and 12 natural products) with stronger binding energies than the reference ligands and known inhibitors of these proteases. These candidates were then evaluated using various filters, including ADMET predictions, drug-likeness assessments, and synthetic accessibility. Among the drugs, silibinin emerged as the leading repurposed candidate, showing promise as a dual inhibitor for SARS-CoV-2 treatment. Additionally, the natural product barettin was highlighted as a strong contender for development into a novel dual-target inhibitor of TMPRSS2 and CTSL.
The growing global population, particularly the increased density of urban areas in developed nations, has inevitably accelerated the transmission of various infectious diseases. Effective treatment of respiratory and gastrointestinal conditions often hinges on antibiotics. However, many viruses have developed resistance to specific antibiotic treatments. Currently, one of the most significant challenges in the pharmaceutical industry is developing and producing novel antibiotic classes. This article examines the properties of a new macrolide antibiotic, novomycin. Macrolides are widely prescribed antibiotics for both adults and children, functioning by disrupting protein synthesis within microbial cells. The study explored the acute and chronic toxicity of novomycin in laboratory animals, its potential allergic reactions on the skin, and its impact on pregnancy and fetal development. Furthermore, the antimicrobial properties of novomycin were investigated. Research into its antimicrobial efficacy revealed that, when administered 3 hours before infection in white mice, novomycin provided 63% protection against Bordetella infections, 44% against Salmonella infections, 56% against Pasteurella infections, and 80% against staphylococcal infections. The findings support the drug’s effectiveness and safety.
Zinc is a crucial element for both plant and human growth, playing a key role in cell division and supporting the maintenance of normal cellular processes. This study investigates the effects of zinc on mitotic division at various concentrations and time points. By assessing the correlation between the mitotic index (MI), chromosomal aberrations (IAC), and exposure time to different concentrations of zinc sulfate (ZnSO4), the cytotoxic effects of ZnSO4 were evaluated. The results showed a strong positive correlation (r > 0.89) between the incidence of chromosomal aberrations and higher concentrations of ZnSO4, suggesting that increased zinc levels contribute to chromosomal damage. Furthermore, increasing exposure time from 24 to 72 hours and concentrations from 10 ppm to 50 ppm resulted in a significant negative correlation (r = -0.84). These results highlight the critical role of zinc in cellular function and the potential harm from excessive zinc.
Parkinson’s disease stands as the second most common neurodegenerative disorder worldwide. This study aimed to assess the impact of DMSO in a rotenone-induced rat model of Parkinson’s disease. DMSO has become a popular agent in preclinical and clinical studies due to its ability to facilitate the transport of poorly soluble drugs across the blood-brain barrier. In this investigation, we explored how a three-week treatment with rotenone, combined with DMSO, influenced hippocampal neuronal activity and the properties of neuronal responses in rats. We specifically compared the toxic effects of rotenone on hippocampal CA1 and CA3 neurons in the presence of DMSO. Our results showed that rotenone induced substantial morphological changes in hippocampal cells. Following DMSO treatment, however, there was a significant restoration of pyramidal cells and Nissl bodies within the CA1 and CA3 regions. DMSO also effectively suppressed both outward and inward currents. Additionally, we recorded spontaneous and evoked spike activity in the hippocampus of rats treated with DMSO (1 ml/kg, administered intraperitoneally for 3 weeks). While rotenone elevated TP and produced a moderate TD effect, DMSO also increased TP but produced a more pronounced TD effect. The analysis indicated inhibitory responses in the hippocampus following high-frequency stimulation (100 Hz for 1 second) of the ipsilateral entorhinal cortex.
The objective of the current study was to investigate the role of the MDH enzyme system in liver cells of alloxan-induced diabetic rats and to examine how the administration of inulin from Jerusalem artichoke affects the enzyme’s activity and gene transcription in these diabetic rats’ livers. In this study, male Wistar rats weighing 150-200 g were selected for the experiment. Diabetes mellitus was induced by a single intraperitoneal injection of 5% alloxan monohydrate (in 0.9% saline). The control group received an equivalent amount of saline solution. Statistical analysis was performed using StatTech v. 1.2.0 software. An increase in NAD-dependent malate dehydrogenase (MDH) activity, accompanied by the emergence of a novel liver isoform, was observed in rats with alloxan-induced diabetes. This finding suggests the potential involvement of the malate dehydrogenase enzyme system in the body’s adaptive response to oxidative stress induced by biochemical changes in diabetic cells. In type I diabetes, this rise in enzyme activity is associated with the appearance of an additional MDH isoform in peroxisomes. Gene expression analysis of mdh1 and mdh2 indicates that diabetes triggers enzyme activation at the gene transcription level. When inulin was administered, it significantly reduced blood glucose levels in rats with alloxan-induced diabetes and restored the regular transcriptional activity of these genes. Consequently, the formation of the new MDH isoform was prevented. This suggests that inulin could be a promising option for pharmacologically managing the metabolic changes associated with diabetes-related pathologies.
This study was conducted to evaluate the safety profile of Pantohematogen, a substance derived from the velvet antlers of the Altai Wapiti, which is commonly used as a functional ingredient in dietary supplements. In this clinical research, both male and female Wistar rats received the maximum tolerable intragastric dose of Pantohematogen. Over the course of six months, researchers monitored the animals for changes in general health status, body mass, hematologic and bone marrow parameters, and the functioning of major organs, including the liver, kidneys, heart, and brain.Throughout the experimental period, the animals exhibited stable behavior and maintained normal fur condition, appetite, reflex responses, and gastrointestinal and urinary tract function. No signs of a toxic response were detected following intragastric administration. However, administration of Pantohematogen at 250 and 500 mg/kg resulted in increased liver mass and reduced testicular size in male rats. This condition persisted for 2 weeks after treatment cessation. Other internal organs showed no abnormalities when compared with control and untreated animals.Importantly, the tested doses exceeded standard human-equivalent levels (per kilogram of body weight) by factors of 2, 10, and 20, respectively. Despite this, the findings indicated no evident toxicological impact from Pantohematogen exposure. This research was conducted at the Tomsk National Research Medical Center of the Russian Academy of Sciences under the supervision of Dr. N.I. Suslov, Doctor of Medical Science.
The administration of sorbents plays a vital role in reducing systemic toxicity after radionuclides or harmful chemicals enter the organism. This study explores the pharmacological characteristics of the newly developed ferrocyanide-bentonite sorbent, Ferbensorb. As a composite formulation, Ferbensorb integrates potassium-iron(III) hexacyanoferrate(II), bentonite, gelatin, along with a mixture of essential macro- and microelements. Experimental assessments were performed using mice and rats as animal models. The investigation evaluated its cesium sorption efficacy, strontium radionuclide retention capability, and performance under simulated associative mycotoxicosis. Autopsies were conducted to assess anatomical alterations, while variations in overall body mass and the condition of specific internal organs were documented. Blood analyses also included profiling of the leukocyte formula. The findings demonstrated that the ferrocyanide-bentonite sorbent, Ferbensorb, effectively alleviated both structural and functional disruptions induced by mycotoxins, including ochratoxin A, fumonisin B, and zearalenone. Improvements were observed in weight gain, innate immune response (indicated by a higher proportion of neutrophils), enhanced serum lysozyme and bactericidal activities, and increased survival rates in the treated animals.
This paper presents the findings of multiple investigations into the newly developed Bentorb sorbent, derived from winemaking byproducts, specifically the adhesive residues of yellow blood salt. Elemental analysis revealed that the predominant components of Bentorb include oxygen, carbon, silicon, aluminum, iron, nitrogen, and magnesium, which together make up the majority of the sorbent’s composition. Toxicological assessments of Bentorb were conducted using laboratory animals. To evaluate acute toxicity, 60 white mongrel rats, each weighing approximately 237 ± 7 g, were subjected to the substance. The results showed no significant changes in the general clinical condition of rats in either the experimental or control groups, and all animals survived the tests. Chronic toxicity was assessed in 60 white mice and 40 Wistar rats, each weighing 185 ± 12 g. Over the study period, no notable differences in health or survival rates were observed between the experimental and control groups. The effects of Bentorb on gastrointestinal function were examined in piglets aged 40-80 days. Additionally, the potential embryotoxicity of Bentorb was investigated in pregnant Wistar rats weighing 200-240 g. The study also included analyses of body weight and various internal organs in both control and experimental groups that received Bentorb.
Assessing erythrocyte acid resistance is a key part of understanding the effects of toxicants on the blood. The objective of this research is to examine both the isolated and combined effects of cadmium, lead, and zinc ions from contaminated drinking water on the acid resistance of erythrocytes in laboratory rats. This investigation was conducted in the Laboratory of Anatomy, Physiology, and Histology at Chechen State University in Grozny, Russia. The study used laboratory rats weighing 100-150 grams, bred in the university’s vivarium. Exposure to metals altered erythrograms, with a noticeable increase in the proportion of erythrocytes with lower resistance and a reduction in hemolysis time. The most considerable alterations were observed after prolonged exposure to Pb2+, Cd2+, Zn2+, and their mixture. After 30 days of exposure to these ions, the peak times for erythrograms were recorded as 0.5 minutes for Pb2+, 1.0 minutes for Zn2+, and 1.5 minutes for Cd2+. The percentage of erythrocytes undergoing hemolysis at these times was significantly higher, being three times more than the control for Pb2+ and Zn2+, and comparable to the control for Cd2+ (36%). Hemolysis times were notably shorter—2.5 minutes for Pb2+ and Zn2+, and 4.5 minutes for Cd2+. By the end of the 30 days, all rats in the heavy-metal exposure group had died. The findings indicate that prolonged exposure to heavy metals induces significant changes in the erythrocyte population and their acid resistance.
Some studies have highlighted the role of Janus kinase 3 (JAK3) in the development of various cancers. To manage this condition, inhibitors such as decernotinib and facitinib are commonly used, although these drugs can cause elevations in liver enzymes and increased lipid levels. It is essential to recognize that new therapies are being developed to inhibit cancer cell growth, using both theoretical and experimental approaches. This study aimed to investigate whether carbazole derivatives (1-25) could interact with JAK3, using the 3pjc protein, decernotinib, and facitinib as reference compounds in the DockingServer tool. The results showed that the carbazole analogs engage with different regions of the 3pjc protein compared to facitinib and decernotinib. Additionally, the inhibition constant (Ki) for carbazole-protein interactions with compounds 2, 5, 9, 17, 18, and 22 was lower than that of the reference drugs, suggesting that these carbazole analogs could be effective JAK3 inhibitors and may help reduce cancer cell growth.
For many years, various drugs have been utilized to treat different cancer types, but some of these treatments come with adverse effects such as liver damage, hypertension, and erectile dysfunction. In the pursuit of alternative therapeutic options, several new compounds have been developed to address this clinical challenge. Yet, the interactions of these compounds with biomolecules involved in cancer development remain largely unclear. With this context in mind, the present study aimed to explore the potential theoretical interaction of a series of pyrimidinone derivatives (compounds 1-27) with the X-linked inhibitor of apoptosis protein (XIAP), a key player in cancer progression, using the Docking model. The findings indicated that certain pyrimidinone derivatives (compounds 1-6, 10, 11, 14, 15, 22-24, 26, and 27) exhibited the ability to bind with the surface of the XIAP protein. In conclusion, these results suggest that some pyrimidinone derivatives may modulate XIAP’s biological activity, making them promising candidates for cancer therapy.
Eurasian Academy of Medicine and Dentistry