Lethal Dose Research Articles

Acute and sub-acute toxicity of ethanol leaf extract from Acrostichum aureum in rats

Acrostichum aureum L. (A.aureum) is a medicinal plant that has anti-cancer, anti-inflammatory, and anti-bacterial activities and has been widely used traditionally in the treatment of many diseases. However, there is a dearth of information on the plant's safety. The present investigation was carried out to evaluate the acute and sub-acute toxicity of ethanol leaf extract of A. aureum (ELAA) in female Sprague Dawley (SD) rats. Oral acute toxicity was studied in female SD rats administered a single dose of 5000 mg kg-1 body weight ELAA. The sub-acute toxicity evaluation was also conducted orally with 100, 200, 500, and 750 mg kg-1 body weight of ELAA for 28 days in female SD rats. The impact of sub-acute treatment on body weight, gross histology, relative organ weight, urinalysis, hematology, plasma biochemistry, and histopathology was assessed following treatment. The ELAA did not cause death or signs of toxicity after acute treatment. Similarly, all the parameters evaluated during acute and sub-acute administration of ELAA did not significantly differ from the control. Therefore, the median lethal dose (LD50) of the ethanol extract of Acrostichum aureum is greater than 5000 mg kg-1 body weight. Its oral sub-acute administration is also non-toxic and safe at the tested doses.

Single-chain A35R-M1R-B6R trivalent mRNA vaccines protect mice against both mpox virus and vaccinia virus

Mpox has spread to many countries around the world. While the existing live attenuated mpox vaccines are effective, advances in 21st century technologies now enable the development of vaccines with more specific antigens, clearer mechanisms, and more controllable side effects. We systematically evaluated the immunogenicity and protective efficacy of the A35R, M1R and B6R antigens of the mpox virus (MPXV). With these findings, we designed three single-chain trivalent mRNA vaccines (AMAB-wt, AMAB-C140S and AMB-C140S) by integrating the soluble regions of these antigens into single mRNA-encoded polypeptides based on their protein structures. Then, the immunogenicity and protective efficacy of these single-chain mRNA vaccines were evaluated in mice models against both VACV and MPXV. The three single-chain vaccines elicited neutralising antibodies that effectively neutralised both VACV and MPXV. The single-chain vaccines or cocktail vaccine containing mRNAs encoding soluble antigen (sA35R+sM1R+sB6R) exhibited 100% or 80% protection against a lethal dose of VACV challenge, while the cocktail of full-length antigens (A35+ M1+ B6) and the live attenuated vaccine, VACV Tian Tan (VACV-VTT), completely failed to protect mice. Moreover, the single-chain vaccines significantly reduced viral load in the lungs and ovaries of MPXV-challenged mice. Compared with the cocktail vaccines, our single-chain designs demonstrated similar or superior immunogenicity and protective efficacy. Importantly, the simplicity of the single-chain vaccines enhances both the controllability and accessibility of mpox vaccines. We believe these single-chain vaccines qualify as the next-generation mpox vaccines. National Natural Science Foundation of China and Youth Innovation Promotion Association of the CAS.

Toxicity of a management bait for grass carp (Ctenopharyngodon idella) incorporated with Antimycin A.

No current technology can specifically target grass carp (Ctenopharyngodon idella) for control within aquatic ecosystems. Rotenone and Carbon Dioxide-Carp are currently the only available registered pesticides for grass carp; they are nonselective and typically applied throughout the water, equally exposing target and native species. A more selective control tool or pesticide application could be used by resource managers to support mitigation efforts. Development of delivery systems that exploit carp feeding strategies could increase selectivity of pesticides and minimize effects on native fishes. A pesticide with selective delivery could be less labor intensive and used within an integrative pest management strategy. The present study examined Antimycin A toxicity in juvenile and sub-adult grass carp and rainbow trout (Oncorhynchus mykiss) across two routes of exposure. Water-based toxicity studies were used to calculate the concentration to cause lethality in 50% of treated fish (LC50) at 24-h, while oral gavage toxicity studies were used to calculate the dose to cause lethality in 50% of treated grass carp and rainbow trout (LD50) 24- to 96-h. Although rainbow trout were more sensitive than grass carp to Antimycin A through water-based exposure, oral toxicity was similar between species, even with inherent gastrointestinal morphological differences. Successful delivery of a lethal dose of Antimycin A to grass carp was achieved through an oral route of exposure using the rapeseed bait and shows promise for registration as a control tool and eventual use in pest management plans. Although a lethal dose of Antimycin A could be incorporated into a single bait pellet, more bait was required to achieve desired mortality when fed to fish under laboratory conditions.

Biological characterization of marine algae and its potent in vitro antioxidant, antimicrobial and larvicidal activity: a focus on Ulva lactuca Linnaeus 1753: 1163.

This study evaluated the biological characteristics of seaweeds Turbinaria ornata, Ulva lactuca, and Gracilaria crassa. Among the seaweeds tested, ethyl acetate extract of Ulva lactuca exhibited the highest antibacterialactivity against Salmonella enterica, Staphylococcus aureus, and Pseudomonas aeruginosa. The phytochemical analysis of ULME and ULEA showed the presence of most of the tested phytochemicals, whereas only amino acids, tannins, glycosides, and carbohydrates were detected by ULHE. The DPPH scavenging property of U. lactuca exerted the maximum antioxidant property of 62.54% (ULME), 75.64% (ULEA), and 39.55% (ULHE), whereas the alpha amylase inhibitory property (µg/mL) of ULME, ULEA, and ULHE was, respectively, 80.99, 51.15, and 49.23. ULME, ULEA, and ULHE exhibited the greatest alpha-glucosidase inhibition, with IC50 values (g/mL) of 116.12, 45.59, and 170.10 correspondingly. ULEA also showed potent mosquito-larvicidal effects against Aedes aegypti larvae with the maximum lethal concentration values with LC50 and LC90 values (mg/mL) being 11.55 and 65.97, respectively. FTIR analysis of ULME, ULHE, and ULEA were found to have various functional groups, including alkanes, carboxylic acids, alkenes, alkynes, aldehydes, amides and alkanes, ketones, and aromatics, while HPLC revealed a strong peak at 4.760 retention time. In conclusion, Ulva lactuca, particularly its ethyl acetate extract, demonstrates significant antibacterial, antioxidant, and enzyme-inhibitory properties, highlighting its therapeutic and biotechnological potential. Its diverse phytochemicals and effective mosquito-larvicidal activity further support its broad application prospects.

Validating an In-House Method for Assessing Effluent Discharge Toxicity Using Acartia tonsa in the Black Sea

The marine copepod Acartia tonsa is an important bioindicator in ecotoxicological studies due to its sensitivity to pollutants and ecological importance. This research evaluates the effects of reference toxicant on the survival of A. tonsa, aiming to validate an in-house method that assesses the sensitivity and reliability of the species for testing in the Black Sea. A. tonsa individuals were exposed in controlled laboratory conditions to varying 3,5-dichlorophenol (reference toxicant) concentrations, with their survival rates monitored over 48 h. Survival data were analyzed to determine the lethal concentration (LC50), a metric for assessing toxicity. The derived LC50 values offer important benchmarks for assessing the environmental impact of different effluent discharges in the Black Sea region. The outcomes will contribute to improving the accuracy and consistency of environmental monitoring and risk assessment practices in the Black Sea region, ensuring that variations in toxicity data are attributable to environmental factors rather than methodological discrepancies.

Enzymological Effects of Lead Acetate Exposure in Various Organs of Oreochromis mossambicus (Peters 1852)

The various enzymological effects of heavy metal Lead acetate (Pb(C2H3O2)2) exposed to fingerlings of Oreochromis mossambicus was analyzed in this study. The 30 days old fingerlings of O. mossambicus were exposed to sub lethal dose 3.80ppm of 96 hrs. LC50 of Pb(C2H3O2)2 for 21 and 28 days, various organs (liver, gill, kidney and muscle tissue) were removed from control and treated fishes and were used for various enzymological effect: Succinate dehydrogenase (SDH), Lactate dehydrogenase (LDH), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Acid phosphatase (ACP) and Alkaline phosphatase ALP). The observed data were subjected into various statistical analysis by using IBM-SPSS version 26. Among the two different exposure periods 21 and 28 days which compared with control fingerlings organs, the various enzymological effects were drastically suffered (Treated fish enzymological levels were inversely proportionate towards the control groups of fish species) by 28 days of exposure periods. Pb(C2H3O2)2 exposed to fingerlings which tested on various organs at 28 days interval periods for assessing of SDH, LDH, AST, ALT, ACP and ALP of various organs of treated fish: Liver: 12.02, 55.75, 58.24, 125.27,12.26, 11.82 µ moles of phenol liberated/ mg of protein; Gill: 10.80, 33.75, 28.73, 28.11, 7.80, 8.63 µ moles of phenol liberated/ mg of protein; Kidney: 12.18, 46.33, 44.78, 75.40, 6.27, 10.38 µ moles of phenol liberated/ mg of protein and Muscle: 11.72, 32.44, 32.76, 44.20, 3.72, 7.20 µ moles of phenol liberated/ mg of protein were recorded on tissue of treated fish. The enzymological effect of Pb(C2H3O2)2 exposed towards O. mossambicus which observed various health defects on organism exposed to a particular toxicant. It may give sufficient information about heavy metal contamination on aquatic organism and would help us to propose policies to protect the ecosystem.

Exogenous Brassinolide Ameliorates the Adverse Effects of Gamma Radiation Stress and Increases the Survival Rate of Rice Seedlings by Modulating Antioxidant Metabolism

Gamma irradiation-based mutant creation is one of the most important methods for rice plant mutagenesis breeding and molecular biology research. Although median lethal dose irradiation severely damages rice seedlings, applying brassinolide (BR) can increase the survival rate of irradiated seedlings. In this study, we investigated the effects of soaking seeds in solutions containing different BR concentrations (0.001, 0.01, 0.1, 1.0, and 5.0 μmol/L) and then spraying the resulting seedlings twice with 0.1 μmol/L BR. The combined BR treatments markedly decreased the superoxide anion (O2•−), hydrogen peroxide (H2O2), and malondialdehyde contents but increased the chlorophyll content. An appropriate BR treatment of gamma-irradiated samples substantially increased the activities of the antioxidant enzymes superoxide dismutase, peroxidase, and ascorbate peroxidase as well as the proline, ascorbic acid, and glutathione contents in rice seedling shoots. The BR treatment also promoted the growth of seedlings derived from irradiated seeds and increased the shoot and root fresh and dry weights. Most notably, soaking seeds in 0.01 or 0.1 μmol/L BR solutions and then spraying seedlings twice with 0.1 μmol/L BR significantly increased the final seedling survival rate and decreased mutant loss. The study results suggest that exogenous BR treatments can protect rice seedlings from gamma irradiation stress by enhancing antioxidant metabolism.

Outer membrane protein C is a protective and unique vaccine antigen against Shigella flexneri 3a

The anti-Shigella vaccine is one of the WHO’s top priorities. Every year the disease kills more than 200,000 people worldwide and poses a serious threat to children under 5 years of age and the elderly. Increasing antibiotic resistance and limitations in diagnostics emphasize the need to develop an effective vaccine. Recent research and clinical trials report multiple approaches used in Shigella-vaccine development. However, despite the efforts of researchers, pharmaceutical companies and health care organizations, there is no licensed vaccine against shigellosis available to the community. Here, we expressed, broadly characterized and demonstrated the protective properties of outer membrane protein C as an effective molecule serving as a universal antigen for Shigella vaccine. Most of the current approaches to the development of Shigella vaccine are based on the polysaccharide antigens, which are serotype specific and have always been challenging in terms of their high specificity, targeting the most exposed surface antigens identified for certain Shigella serotypes. Here, we confirm immunogenic and protective properties of the recombinant OmpC protein, which protects mice against a lethal dose of a virulent strain 2 weeks after active immunization.

Extraordinary variance in meta-analysis of venom toxicity of 160 most lethal ophidians and guidelines for estimating human lethal dose range

Background: This is the first meta-analysis to characterize intra-ophidian-species variation in whole venom. Being the largest possible meta-analysis at this time, it encompasses all known records of animal lethality studies over the past 100 years. These results were not artifacts of resistant test-animal species and showed orders of magnitude beyond the 1.6 logs (40-fold change) range of lethal dose documented in the literature between amphibians, lizards, and mice. Methods: A total of 1003 lethal dose study results for 160 of the most lethal venomous ophidian species in the world were analyzed. Results: LDLo was not different from LD50 across studies, indicating the true range of toxicity is probably larger. The belief that, for the route of inoculation, IC < IV < IP < IM < SC was well supported (R2 = 0.90). However, 5% of ICs were the highest dose, and 7% of SC inoculations were the lowest dose. Within the mouse test species, for one route of inoculation, the widest LD range was 2.96 logs (917-fold change, N = 20). Within mouse species, for multiple routes of inoculation, the widest LD range was 3.6 logs (4,150-fold change, N = 20). The strongest correlation for the range of lethal dose results was the number of studies (R2 = 0.56), followed by the number of test-animal species (R2 = 0.55) and then the number of routes of inoculation (R2 = 0.43). Conclusion: Scientists working with humans should use combined LDLo and LD50 meta-datasets for all data and calculate mean, median, minimum, range, and standard deviation as shown in the supplement spreadsheet, and the equations we provide. Standard deviation multiples may provide the desired safety for experimenters. For estimating the LD50 range and minimum lethal dose for species with little data, we recommend curating a meta-dataset of related snakes, and computational research to strengthen this estimation.

Understanding the potential of coal gangue as photocatalyst for antibiotic degradation: The role of abundant oxygen vacancies and electron-hole pairs

Coal gangue (CG) offers promising potential as a cost-effective photocatalyst for antibiotic degradation. However, current approaches do not emphasize the origin of its photocatalytic activity. This study investigates the photocatalytic activity of CG through a comparative analysis with one-pot aerobic/anaerobic calcinated CG. The potential application of CG as a photocatalyst for tetracycline (TC) decontamination in water was evaluated under dark and light. Characterization results identified anatase and kaolinite as the critical photosensitive minerals in CG. Batch removal experiments indicated that CG achieved up to 98 % TC removal at 1 g/L dosage, with most biotoxic intermediates reduced to below 0.9 mg L−1 Lethal Concentration 50 (LC50) of Fathead minnow (Pimephales promelas). Degradation pathways identified by density functional theory (DFT) and quantitative structure-activity relationship (QSAR) indicated that superoxide anion (⁎O2−) and electron-hole (e−-h+) pairs were predominant contributors to TC photodegradation. Theoretical calculations suggest that the oxygen vacancies on the CG surface can accelerate the production of ⁎O2−, while fast electron transport channels within surface hydroxyl groups facilitate e− and h+ separation. The findings of this research elucidate the origin of CG's photocatalytic activity and highlight the potential to serve as a photocatalyst for low-cost antibiotic removal, offering a promising solution for coal waste management and utilization.

Unveiling the Larvicidal Potential of Golpar (Heracleum persicum Desf. ex Fisch.) Essential Oil and Its Main Constituents on Aedes and Anopheles Mosquito Vectors

Natural products are thoroughly studied as valuable alternatives to synthetic insecticides. Heracleum persicum Desf. ex Fisch. (Apiaceae), commonly known as Golpar, is an Iranian medicinal plant largely employed as a spice, which has previously revealed insecticidal potential. The chemical composition of H. persicum essential oil (EO) was investigated by GC-MS and was mainly dominated by hexyl butyrate (36.1%) and octyl acetate (23.7%). The EO and its main esters were tested on three mosquito species. Aedes aegypti (L.) larvae were the most sensitive to all tested products. Lethal concentrations (LC50) of 59.09, 53.59, and 47.05 ppm were recorded for the EO, hexyl butyrate, and octyl acetate, respectively. Aedes albopictus (Skuse) and Anopheles gambiae Giles demonstrated comparable sensitivity to the EO, with LC50 values of 102.97 and 97.91 ppm, respectively, whereas the isolated constituents appeared more active on An. gambiae (LC50 of hexyl butyrate and octyl acetate of 70.97 and 60.71 ppm, respectively) with respect to Ae. albopictus (LC50 of hexyl butyrate and octyl acetate of 85.40 and 91.38 ppm, respectively). Low toxicity was registered for both EO and single components against human embryonic kidney (HEK293) cells. Overall, the H. persicum EO, hexyl butyrate, and octyl acetate could be further considered for larvicide development.

Effects of acute gamma irradiation on the morphology of Curcuma alismatifolia ‘Siam Shadow’ and C. alismatifolia ‘Siam Scarlet’

Curcuma alismatifolia (Pathumma in Thailand), also known as Siam Tulip, is an economically valuable cut flower in Thailand and is continuously bred to enhance its captivating array of colors. This study aimed to investigate the effects of acute gamma irradiation on 2 cultivars of C. alismatifolia ‘Siam Shadow’ and C. alismatifolia ‘Siam Scarlet’ for in vitro propagation and determination of the lethal dose 50 (LD50). The irradiation was conducted at doses of 0, 20, 30, 40 and 80 Gy using young shoots tissue culture. The results of the experiment revealed that the LD50 for ‘Siam Shadow’ could not be determined while ‘Siam Scarlet’ was 29.06 Gy. ‘Siam Shadow’ exhibited chimera leaf formation when exposed to a gamma irradiated dose of 40 Gy, while ‘Siam Scarlet’ exhibited chimera leaf formation when gamma irradiated at doses of 20 Gy in vitro. After planting in a greenhouse, ‘Siam Shadow’ was irradiated with 30 Gy of gamma irradiated, had reduced bract numbers and the bracts became smaller. Conversely, ‘Siam Scarlet’ irradiated with 20 Gy of gamma irradiated, produced smaller inflorescences with only 2 bracts, while irradiation with 30 Gy resulted in 2 lobes and spotted leaves at the edges of the leaves. The results indicated that both the C. alismatifolia cultivars and gamma irradiation rates had a significant influence on survival rate, number of shoots, plant height, chlorophyll mutants and morphology. As the outcome, it was determined that gamma irradiation with optimum doses of gamma rays could induce new characteristics in C. alismatifolia.

The Ecotoxicity of Pesticides Used in Conventional Apple and Grapevine Production in Austria Is Much Higher for Honeybees, Birds and Earthworms than Nature-Based Substances Used in Organic Production

It is debated whether the ecotoxicity of active substances (ASs) contained in synthetic pesticides applied in conventional agriculture (conASs) differs from nature-based ASs used in organic agriculture (orgASs). Using the official pesticide use statistics, we evaluated the ecotoxicity of ASs used in apple and grapevine production in Austria. In 2022, 49 conASs and 21 orgASs were authorized for apple production and 60 conASs and 23 orgASs were authorized for grapevine production in Austria. Based on the latest publicly available data on the actual use of pesticides in apple and grapevine production (from the year 2017), we evaluated their ecotoxicity based on information in the freely accessible Pesticide Properties and Bio-Pesticides Databases. The results showed that although the amount of ASs applied per hectare of field was higher in organic farming, the intrinsic toxicities of ASs used in conventional farming were much higher. The number of lethal toxic doses (LD50) of ASs applied in conventional apple orchards was 645%, 15%, and 6011% higher for honeybees, birds, and earthworms, respectively, than in organic apple production. In conventional vineyards, lethal doses for honeybees, birds, and earthworms were 300%, 129%, and 299% higher than in organic vineyards. We conclude that promoting organic farming would therefore contribute to the better protection of biodiversity on agricultural land and beyond.

Effects of the combination of anti-PcrV antibody and bacteriophage therapy in a mouse model of Pseudomonas aeruginosa pneumonia.

Acute lung injury caused by Pseudomonas aeruginosa is attributed to the translocation of cytotoxin into pulmonary epithelial cells via the P. aeruginosa type III secretion system. This virulence can be blocked with a specific antibody against PcrV in this secretion system. However, because anti-PcrV antibodies do not have bactericidal activity, the treatment of bacteria depends on the phagocytic system of the host. In this study, we investigated the therapeutic effect of combination therapy with an anti-PcrV antibody and bactericidal bacteriophages on acute lung injury and subsequent death in mice compared with a single treatment. After the mice intratracheally received a lethal dose of the cytotoxic P. aeruginosa strain, a second instillation was performed with saline, anti-PcrV IgG, bacteriophages, or a mixture of anti-PcrV and bacteriophages. The survival rates 24 h after infection were as follows: 7.1% in the saline group, 26.7% in the anti-PcrV group, 41.2% in the phage group, and 66.7% in the anti-PcrV + phage group (P < 0.001 vs saline-treated group). The activity of surviving mice in the anti-PcrV + phage group was significantly greater than that in the saline group. The lung weight in the anti-PcrV + phage group was significantly lower than that in the anti-PcrV group. In conclusion, combination therapy with an anti-PcrV antibody and a bacteriophage reduces acute lung injury and suggests improved survival compared with each treatment alone. This combination therapy, which does not rely on conventional antibiotics, could constitute a new strategy for treating multidrug-resistant P. aeruginosa infections.IMPORTANCECombination therapy with either bacteriophages alone or in combination with anti-PcrV antibodies in a mouse model of Pseudomonas aeruginosa pneumonia may reduce the acute lung injury and improve survival. This combination therapy, which does not rely on conventional antibiotics, may be a new strategy to treat multidrug-resistant Pseudomonas aeruginosa infections.

Cryptococcus neoformans infections: aspartyl protease potential to improve outcome in susceptible hosts.

Vaccination and immunotherapies against fungal pathogens still remain a challenge. Here, we show using an in vivo model based on outbred mice that development of antibodies against Pep1p, an antigenic protein of the fungal pathogen Cryptococcus neoformans, confers resistance to this fungal infection. In support of this observation, prophylactic or therapeutic immunization of the mice with recombinant Pep1p could improve their survival when infected with a lethal dose of C. neoformans. Moreover, passive therapy with monoclonal anti-Pep1p antibodies also enhanced survival of the mice from C. neoformans infection. The associated antifungal mechanisms were mounting of a protective immune response and the development of fungal specific antibodies that decrease the fungal burden due to an increase in their phagocytosis and/or inhibit the fungal multiplication. Together, our study demonstrates (a) the mode of host-fungal interaction and the immune response developed thereby play a crucial role in developing resistance against C. neoformans; (b) Pep1p, an aspartic protease as well as an antigenic protein secreted by C. neoformans, can be exploited for vaccination (both prophylactic and therapeutic) or immunotherapy to improve the host defense during this fungal infection.

Identifying and modeling the impact of neonicotinoid exposure on honey bee colony profit

Abstract Pollination by the European honey bee, Apis mellifera, is essential for the production of many crops, including highbush blueberries (Vaccinum corymbosum). To understand the impact of agrochemicals (specifically, neonicotinoids, a class of synthetic, neurotoxic insecticides) on these pollinators, we conducted a field study during the blueberry blooms of 2020 and 2021 in British Columbia (B.C.). Forty experimental honey bee colonies were placed in the Fraser Valley: half of the colonies were located within 1.5 km of highbush blueberry fields (“near” colonies) and half were located more than 1.5 km away (“far” colonies). We calculated risk quotients for these compounds using their chronic lethal dietary dose (LDD50) and median lethal concentration (LC50). Pesticide risk was similar between colonies located near and far from blueberry forage, suggesting that toxicity risks are regionally ubiquitous. Two systemic neonicotinoid insecticides, clothianidin and thiamethoxam, were found at quantities that exceeded chronic international levels of concern. We developed a profit model for a pollinating beekeeper in B.C. that was parameterized by: detected pesticide levels; lethal and sublethal bee health; and economic data. For colonies exposed to neonicotinoid pesticides in and out of the blueberry forage radii, there were economic consequences from colony mortality and sublethal effects such as a loss of honey production and compromised colony health. Further, replacing dead colonies with local bees was more profitable than replacing them with imported packages, illustrating that beekeeping management selection of local options can have a positive effect on overall profit.

Cloperastine Reduces IL-6 Expression via Akt/GSK3/Nrf2 Signaling in Monocytes/Macrophages and Ameliorates Symptoms in a Mouse Sepsis Model Induced by Lipopolysaccharide.

Cloperastine (CLP) is a drug with a central antitussive effect that is used to treat bronchitis. Therefore, we have attempted to examine the anti-inflammatory effects of CLP. CLP reduced the secretion of interleukin (IL)-6, a pro-inflammatory cytokine, from RAW264.7 monocyte/macrophage-linage cells treated with lipopolysaccharide (LPS). IL-6 is a biomarker of sepsis and has been suggested to exacerbate its symptoms. We found that the intraperitoneal administration of CLP reduced IL-6 levels in the lungs and also improved hypothermia in mice with LPS-induced sepsis. CLP ameliorated kidney pathologies such as congestion and increased the survival rate of mice administered with a lethal dose of LPS. To reveal the mechanisms underlying the anti-inflammatory function of CLP, we analysed the intracellular signaling in LPS-treated RAW264.7 cells. CLP induced the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase 3 (GSK3) and also increased the amount of nuclear factor erythroid-2-related factor 2 (Nrf2) in RAW264.7 cells with/without LPS. Wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K), reduced the upregulated phosphorylation levels of Akt and GSK3 and the increased amount of Nrf2. It also halted the reduction of IL-6 secretion caused by CLP. These results suggest that CLP has an anti-inflammatory function via Akt/GSK3/Nrf2 signaling and could be a candidate drug for the treatment of inflammatory diseases, including sepsis.

The Effects of Ubiquinone on the Antioxidant System in Male Rats Exposed to Saccharin-Induced the Hepatic Toxicity

Saccharin (Sac) is a widely used artificial sweetener with significant applications in the food industry, pharmaceutical formulations, and tobacco products. Despite its popularity, saccharin has drawn attention due to its potential carcinogenic effects and associations with various health risks, including renal impairment, hepatic dysfunction, obesity, and diabetes. This study aimed to investigate the protective effects of Ubiquinone, or coenzyme Q10 (COQ10), on liver toxicity induced by saccharin, focusing on oxidative stress and antioxidant markers. In this experiment, rats were divided into six groups of ten. The control group received no treatment, while the second group was administered COQ10 at a dosage of 20 mg per kilogram of body weight. The third and fourth groups were given saccharin at 1/10 and 1/20 of the lethal dose 50 (LD50), respectively. The fifth and sixth groups received saccharin at the same dosages as the third and fourth groups, but with additional COQ10 supplementation. All treatments were administered orally for 30 days, after which liver tissues were collected to assess oxidative stress and antioxidant markers. The results revealed that saccharin significantly increased oxidative stress in the liver, as evidenced by elevated levels of malondialdehyde (MDA) and oxidized glutathione (GSSG). Additionally, saccharin-treated groups exhibited a marked decrease in antioxidant markers, including reduced glutathione (GSH) and superoxide dismutase (SOD). However, the groups that received COQ10 alongside saccharin showed significant improvement, with oxidative stress and antioxidant levels nearly returning to those observed in the control group. These findings suggest that saccharin consumption promotes the generation of reactive oxygen species and contributes to liver damage, characterized by necrotic hepatocytes, sinusoidal dilatation, and inflammatory infiltration. The protective effects of COQ10 in mitigating saccharin-induced oxidative stress highlight its potential as a therapeutic agent for preventing liver damage associated with saccharin intake.

Anticancer potentiality of Hottentotta saulcyi scorpion curd venom against breast cancer: an in vitro and in vivo study.

Scorpion venom may include pharmacological substances that have the potential to provide benefits. Multiple scientific investigations have shown that particular scorpion venoms induce apoptosis and inhibit the development of cancerous cells. The present study investigated the potential anticancer properties of the crude venom derived from Hottentotta saulcyi (H. saulcyi) on both in vivo mice models and in vitro breast carcinoma cells. The venom of scorpions belonging to the species H. saulcyi was obtained with the application of electrical stimulation at voltages of 8 and 10V. The determination of the Average Lethal Dose 50 (LD50) was conducted. The present work assessed the in vitro cytotoxicity and morphological characteristics of H. saulcyi venom using fluorescence microscopy, MTT assay, and flow cytometry assessment. Additionally, research was performed to assess the cytotoxic effects in vivo on a mouse model with breast cancer. The examination of MCF-7 cells treated with scorpion venom at a microscopic level revealed the existence of cells undergoing apoptosis. The venom of H. saulcyi has anticancer properties, as shown by the observation that MCF-7 cells had a 62.12% apoptotic rate when exposed to a dose of 1.47mg/L. Based on the results obtained, it can be shown that the viability of MCF-7 cells has exhibited a substantial reduction (P < 0.01). Furthermore, the findings indicated that the venom of H. saulcyi resulted in a significant increase in the synthesis of TNF-α, IL-6, IL-10, TGF-β, and caspase (P < 0.05). The treatment groups administered with H. saulcyi venom exhibited a significant augmentation in the expression of proapoptotic genes compared to the control group of healthy individuals. The transcription of the BCL2 gene exhibited a statistically significant increase in the healthy control group compared to both the healthy venom-treated group (P < 0.05) and the malignant venom-treated group (P < 0.01). The crude venom of H. saulcyi has considerable promise in demonstrating anticancer properties. Further investigation may be warranted to explore the potential of using H. saulcyi crude venom as a medicinal platform for the prevention of breast cancer.

A Zebrafish Embryo Model to Screen Potential Therapeutic Compounds in Sapindaceae Poisoning

Hypoglycin A (HGA) and methylenecyclopropylglycine (MCPrG) are protoxins produced by Sapindaceae plants, particularly Acer pseudoplatanus, and are responsible for causing atypical myopathy (AM) in equids. These protoxins metabolise into toxic compounds, such as methylenecyclopropylacetyl-CoA (MCPA-CoA), which alters energy metabolism and induces severe rhabdomyolysis. Currently, no specific treatment exists for this poisoning, in vitro models fail to reproduce HGA’s toxic effects on equine primary myoblasts, and mammalian models are impractical for large-scale drug screening. This study aimed to develop a zebrafish embryo model for screening therapeutic compounds against AM. Zebrafish embryos were exposed to various concentrations of HGA, MCPrG, and methylenecyclopropylacetate (MCPA) for 72 h. MCPrG did not induce toxicity, while HGA and MCPA showed median lethal concentration (LC50) values of 1.7 µM and 1 µM after 72 h, respectively. The highest levels of the conjugated metabolite MCPA–carnitine were detected 24 h after HGA exposure, and the acylcarnitines profile was highly increased 48 h post-exposure. Isovaleryl-/2- methylbutyrylcarnitine levels notably rose after 24 h, suggesting potential exposition biomarkers. Glycine and carnitine effectively reduced mortality, whereas riboflavin showed no protective effect. These findings suggest that the zebrafish embryo represents a valuable model for identifying therapeutic compounds for Sapindaceae poisoning.