Toxicity assessment of gelsenicine and the search for effective antidotes

Background Gelsenicine, one of the most toxic alkaloids of Gelsemium elegans Benth ( G. elegans), causes severe respiratory depression. However, its toxicity mechanisms are yet to be elucidated and no effective antidotes are available. Objective This study aimed to analyse the toxicity characteristics of gelsenicine. Methods Both acute and sub-acute toxicities were evaluated. Gelsenicine distribution and elimination in the central nervous system (CNS) and blood were observed. Effective antidotes for gelsenicine poisoning were screened. Results In the acute toxicity study, gelsenicine was highly toxic, and female rats exhibited greater sensitivity to gelsenicine than male rats (LD50 0.520 mg/kg vs 0.996 mg/kg, respectively). Death was primarily caused by respiratory failure. However, in the sub-acute toxicity study, no significant organ damage was observed. Gelsenicine was easily absorbed from the gastrointestinal tract and penetrated the blood–brain barrier, reaching peak concentrations in the CNS within 15 min and rapidly decreasing thereafter. Flumazenil or diazepam combined with epinephrine reversed gelsenicine toxicity and significantly improved survival rate in mice. Conclusions Gelsenicine is a highly toxic substance that affects nerve conduction without causing damage; the potential toxic mechanism is possibly associated with GABAA receptors. Our findings provide insights into the clinical treatment of gelsenicine -related poisoning and its toxicity mechanisms.

Analysis and risk assessment of arsenic in the water sources of the cities Cuenca and Azogues, Ecuador

Arsenic (As) is a toxic element present in the environment posing a threat to consumers health. To identify the arsenic content in rivers, páramos, and wells in the city of Cuenca, and in rivers in the city of Azogues, two monitoring campaigns in the period August-November 2017 were conducted, respectively during a low and high flow hydrological period. The measurements encompassed physicochemical quality indicators such as pH, color, turbidity, and conductivity. Results show that the páramos and wells are free of As, while this toxic substance is present in surface water with higher levels in periods of high flow. A significant association between the concentration of As and the pH of river water was found. The risk of chronic toxicity from consumption is almost non-existent because the observed As levels exceed only exceptionally the permissible limit established by the Ecuadorian TULSMA (Unified Text of Secondary Environmental Legislation) regulation. The presence of As in surface water is the result of anthropological activities such as the use of pesticides. A permanent monitoring of the quality of water resources for human consumption is necessary, particularly in the rainy season, due to the diffuse and difficult to control pollution processes.

The Acute Toxicity of Rutin in Mice

Acute toxicity is a step to evaluate the toxicity of a substance. Rutin is one of the flavonoid compounds with a variety of pharmacological effects. The aim of the study is to calculate the lethal dose that affect fifty percent of the mice used in the experiment (LD50). Thirty Swiss albino male and 30 non-pregnant female mice have been divided equally and randomly into 5 treated groups and one control group (n=5) Rutin has been administered with concentrations 5, 2.5.1.25,0.625 and 0.312 g/kg administered as a single dose intraperitoneally (IP) while the control group received 1% DMSO (IP). Animals were observed for any morbidity and mortality for 14 days. After 14 days the animal blood collected for biochemical and hematological analysis then all animals are euthanized for histopathological evaluation. The results showed the LD50 was 1.51 g/kg for male mice while for female mice was1.49 g/kg. No significant changes were observed at dose of 1.25glkg (female) and 0.625, 0.312 glkg (both sexes) in body weight measurements and in biochemical or hematological assays. Moreover no significant histopathological changes were reported compared to control.. It can be concluded that Rutin is practically a non-toxic substance.

Characterizing the Role of Glutamine synthetase Gene on Ammonia Nitrogen Detoxification Metabolism of the Razor Clam Sinonovacula constricta

Ammonia nitrogen is a common toxic substance in the aquatic system, which seriously threatens the survival and growth of clams. However, less is known about the ammonia metabolism and detoxification strategy in razor clam. In this study, the polymorphism of the Glutamine synthetase gene from Sinonovacula constricta (Sc-GS) was found to be related to ammonia tolerance. By comparing the coding sequence (CDS) region of Sc-GS from two geographical populations, a total of 14 and 12 single nucleotide polymorphisms (SNPs) were identified, respectively, of which 10 loci were shared between the two populations. Among them, the locus c.1133T > G exhibited an extremely significant and strong association with ammonia tolerance in both populations (P < 0.01), and it was missense mutation, which led to the amino acid change from leucine (Leu) to arginine (Arg). Furthermore, the results about H&E staining and immunohistochemistry of Sc-GS protein in gills and hepatopancreas revealed that it was specifically localized in the lateral cilia of gill filaments and the endothelial cells of hepatocytes. After inhibiting the Sc-GS expression by RNA interference (RNAi) technology, the transcript levels of Sc-GS were extremely significantly downregulated at 24, 48, 72, and 96 h (P < 0.01) in the hepatopancreas. Taken together, these results indicated that the Sc-GS gene may participate in ammonia metabolism. In addition, these results will help to demonstrate the role of Sc-GS in ammonia nitrogen metabolism and provide markers related to ammonia nitrogen tolerance for molecular marker-assisted selection (MAS) of the razor clam.

Characterization of Polyphenol and Volatile Fractions of Californian-Style Black Olives and Innovative Application of E-nose for Acrylamide Determination

Californian-style black olives require a sterilization treatment that produces a carcinogenic contaminant, acrylamide. Thus, this compound was evaluated in two different olive cultivars using an electronic nose (E-nose). The sterilization intensity had a significant influence on the final phenol concentrations, acrylamide content, and volatile compounds. Increasing the sterilization intensity from 10 to 26 min (F0) reduced the phenol content, but it promoted acrylamide synthesis, leading to a wide range of this toxic substance. The Ester and phenol groups of volatile compounds decreased their content when the sterilization treatment increased; however, aldehyde and other volatile compound groups significantly increased their contents according to the thermal treatments. The compounds 4-ethenyl-pyridine, benzaldehyde, and 2,4-dimethyl-hexane are volatile compounds with unpleasant odours and demonstrated a high amount of influence on the differences found after the application of the thermal treatments. The “Manzanilla Cacereña” variety presented the highest amount of phenolic compounds and the lowest acrylamide content. Finally, it was found that acrylamide content is correlated with volatile compounds, which was determined using multiple linear regression analysis (R2 = 0.9994). Furthermore, the aroma of table olives was analysed using an E-nose, and these results combined with Partial Least Square (PLS) were shown to be an accurate method (range to error ratio (RER) >10 and ratio of performance to deviation (RPD) >2.5) for the indirect quantification of this toxic substance.

Study on the perspectives of application of eco-friendly laser biotechnology for environmental protection in Uzbekistan

Since few decades, the world is encountering unusual and daunting environmental challenges like global warming, climate change, pollution of the atmosphere and water, an emerging international crisis in water availability, long-term damage to ecosystems and substantial loss of biodiversity, waste production and disposal, damaged aquatic ecosystems, impacts of chemicals use and toxic substance disposal, as well as land degradation and deforestation. Accordingly, Uzbekistan has also been encountering some environmental issues, such as global Aral Sea crisis, soil erosion and desertification, wastewater, air pollution and a growing amount of municipal solid waste. Hence, this paper illustrates the major environmental challenges and risks in Uzbekistan, as well as, the possible application of environmentally friendly laser biotechnology for more efficient and rationale protection of ecosystems and wide-scale reclamation of deteriorated areas. Comprehensive use of laser irradiation can be effectively applied in environmental protection engineering and technologies for sustainable development in selected regions. Laser irradiation or photostimulation is a neoteric area and process of environmental biotechnology. In this process, coherent laser light is employed to optimize the natural processes involved in the bioremediation of xenobiotics or bioaccumulation of metals. Additionally, laser biotechnology could be broadly used for more efficient reclamation of contaminated soil, wastewater treatment, as well as for increasing the growth rate of irradiated plants and their resistance to various macro- and micro pollutants in the air, soil, and water.

Toxic Substance-induced Hippocampal Neurodegeneration in Rodents as Model of Alzheimer’s Dementia

BACKGROUND: Alzheimer’s Dementia (AD) cases are increasing with the global elderly population. To study the part of the brain affected by AD, animal models for hippocampal degeneration are still necessary to better understand AD pathogenesis and develop treatment and prevention measures. AIM: This study was a systematic review of toxic substance-induced animal models of AD using the Morris Water Maze method in determining hippocampal-related memory impairment. Our aim was reviewing the methods of AD induction using toxic substances in laboratory rodents and evaluating the report of the AD biomarkers reported in the models. METHODS: Data were obtained from articles in the PubMed database, then compiled, categorized, and analyzed. Eighty studies published in the past 5 years were included for analysis. RESULTS AND DISCUSSION: The most widely used method was intracerebroventricular injection of amyloid-β _substances. However, some less technically challenging techniques using oral or intraperitoneal administration of other toxic substances also produce successful models. Instead of hippocampal neurodegeneration, many studies detected biomarkers of the AD pathological process while some reported inflammation, oxidative stress, neurotrophic factors, and changes of cholinergic activity. Female animals were underrepresented despite a high incidence of AD in women. CONCLUSION: Toxic substances may be used to develop AD animal models characterized with appropriate AD pathological markers. Characterization of methods with the most easy-handling techniques and more studies in female animal models should be encouraged.

Effective removal of mercury (Hg) from sediment by acid extraction

Mercury (Hg) is a hazardous and toxic substance that is resistant to decomposition and can accumulate in sediment and enter the living organisms via food chain. Due to the status of level mercury in Indonesia has reached the warning level, the action should be taken to avoid any negative impact on the environment and human health. The purpose of this study to developed a simple, fast, and effective sediment washing method for Hg removal using acid extraction. The results showed that pollution level of sediment in Ciujung watershed and its tributaries was high, especially the pollution of Hg and Cd, according to geoaccumulation index (I geo) and potential ecological risk index (PERI). By the proposed method, Hg-contaminated sediment can be extracted within 21 minutes with 99.5% of extraction rate. CRM ERM CC580 (estuarine sediment) was used for validating the results. The optimal conditions such as vortex time, acid concentration, sonication time were evaluated according to analytical parameters. The method is valuable for designing a remediation protocol for sediment washing in developing countries.

Dichloroethane poisoning

Diagnosis and treatment of acute poisoning from dichloroethane remain a very urgent task for clinical toxicology and clinical laboratory diagnostics since it belongs to the group of potent poisonous substances, the poisoning from which is the most severe. Dichloroethane belongs to organochlorine compounds and is a volatile liquid with a specific aromatic odor, very soluble in alcohol and fats. This substance is used not only for industrial purposes but also for household purposes. It is used as a raw material for the production of plastics. It has a fragrant odor, promotes ingestion for intoxication. Dichloroethane is produced in huge quantities and is used in the production of polyvinylchloride and other polymeric materials, fumigants, and adhesives. Death can occur even after taking 10–20 ml of dichloroethane. When ingested, the maximum concentration of substances in the blood is reached after 3–4 hours from the moment of taking, and the rate of absorption increases when taken together with alcohol and fats. Absorbed into the blood, toxic substances accumulate in lipid-rich tissues (brain, liver, omentum, adrenal glands). The toxicity of dichloroethane is due to its metabolism into chloroethanol and monochloroacetic acid, which on the first day determine the clinical picture of a narcotic and depressive effect on the central nervous system and exotoxic shock (at doses exceeding lethal doses), toxic liver dystrophy (on days 2–5), toxic nephropathy, gastrointestinal syndrome. Preventive measures for dichloroethane poisoning include compliance with all safety rules at work and home. Employees of enterprises dealing with this toxic substance must work in rooms with constantly forced ventilation, in industrial filter respirators (gas masks), and protective clothing.

Preclinical safety evaluation of drone brood homogenate and justification of pharmacological action

The problem of studying the metabolic syndrome, as well as its integration into other pathological processes, despite large-scale research, remains relevant. The complexity of the interaction of different links in pathogenesis requires scientists to find new tools and methods for both diagnosis and treatment. Drone brood homogenate, which is a multifactorial pharmacological agent in terms of chemical composition, seems to be promising to study for today. And the lack of contraindications and a wide age range makes it an excellent object of research. The current study evaluated the pharmacological aspects of safety: acute toxicity, effects on the functional and motor activity of the gastrointestinal tract, as well as local irritation of the gastric mucosa, the secretory function of the stomach. All experiments were performed according to the classical methods. The specific pharmacological activity of the drone brood homogenate was determined in comparison with metformin in the experimental fructose metabolic syndrome. Animals obtained from the Vivarium of I.Horbachevsky Ternopil National Medical University were used to implement the set goals. Working with animals was met all bioethical requirements. The study found that the lyophilized drone brood homogenate does not have a local irritant effect and does not cause ulcers on the surface of the gastric mucosa, does not affect the secretory function of the stomach and motor-evacuatory activity of the gastrointestinal tract and is a low-toxic substance, indicating the possibility of its long-term safe use. As expected, glucose, insulin, and HOMA index were significantly increased in animals that were simulated metabolic syndrome. The use of drone brood homogenate by animals contributed to a relatively positive effect on selected indicators of the metabolic syndrome. Accordingly, drone brood homogenate is a promising active pharmaceutical ingredient for the normalization of biochemical disorders in metabolic syndrome.