Low Acute Toxicity Research Articles

Acute, chronic, and behavioral toxicity of fluorine-free foams to earthworm species Eisenia fetida and Dendrobaena veneta

Aqueous film-forming foams (AFFF) containing per- and polyfluoroalkyl substances (PFAS) are widely used as fire suppressants. Due to rising health and environmental concerns, fluorine-free foams (F3) are being developed and tested as safer alternatives. However, the impact of these replacement products on ecologically important earthworms has not been adequately studied. This study addresses this gap by comparing the acute, chronic, and behavioral effects of two F3 formulations, BioEx Ecopol and Angus Fire Jetfoam, with a commonly used PFAS-containing AFFF, Buckeye, on two species of earthworms. Soil treated with BioEx Ecopol and Buckeye at the maximum 3% concentration did not cause significant acute mortality in Eisenia fetida, whereas Angus Fire Jetfoam resulted in 100% mortality at the same concentration. In a 28-day chronic test, weight loss was observed in Dendrobaena veneta worms exposed to soil treated with Angus Fire Jetfoam. Additionally, both Eisenia fetida and Dendrobaena veneta demonstrated almost complete avoidance of soils treated with any of the three foams at 3% concentration, indicating potential ecological effects despite lack of acute toxicity by two of the products. The differences in toxicity are likely due to the distinct chemical compositions and surfactant concentrations in these foams. BioEx Ecopol and Buckeye, despite their differing surfactant mixtures, exhibited lower acute toxicity, whereas Angus Fire Jetfoam's high mortality rate points to a potentially problematic chemical formulation. By understanding the toxicity of current formulations, this study supports the ongoing development and evaluation of new fire suppression products, supporting the creation of safer technologies.

Ethnopharmacological Study of Garrya laurifolia and Its Antidiabetic Effect in Rats.

This study aimed to scientifically validate the traditional use of Garrya laurifolia (Gl) leaves as an antidiabetic agent attributed to a community in Mexico. The descriptive ethnobotanical study was conducted in San Miguel Tecpan, a municipality of Jilotzingo, State of Mexico, Mexico, where a structured questionnaire was applied to 44 inhabitants. In vivo studies evaluated the acute oral toxicity of Gl leaves in murine and the effects of a leaf infusion on glycemia in normoglycemic and diabetic rats; in addition, the interaction between Gl and metformin (Met) was also evaluated. The in vitro antioxidant activity of Gl was determined. The phytochemical screening and quantification of phenolic and flavonoid content of Gl leaves were performed. Gl had a high relative frequency of citation (0.68) among respondents. Gl had a low acute toxicity risk with LD50 > 5000 mg/kg. The extract had no hypoglycemic effect in normoglycemic rats, but it did have hypoglycemic and antihyperglycemic effects (250 and 500 mg/kg) in diabetic rats. The interaction between Gl (500 mg/kg) + Met (300 mg/kg) resulted in antidiabetic synergism. Gl showed strong antioxidant activity (93.1 ± 0.4%). Phytochemical screening revealed the presence of alkaloids, flavonoids, and some other phenolic compounds. The total phenol content was 77.9 ± 0.6 mg EQ/g and 87.7 ± 0.7 mg EAG/g, and the flavonoids content was 5.32 ± 0.2 mg EQ/g. UHPLC-MS/MS analysis identified chlorogenic acid, rutin, aucubin, luteolin 7-O-neohesperoside, and myricitrin. The findings support the potential use of Gl as a safe and effective antidiabetic agent.

Toxicity of the microencapsulated extract of seeds of Annona muricata L. (Annonaceae) on Africanized honey bees

Pesticide toxicity is one of the causes of pollinator decline worldwide. Here we evaluate the chronic (for seven days) and acute (for one day) toxicity of a microencapsulated formulation (MF) obtained from Annona muricata seeds on Apis mellifera in concentrations of 0.157 and 2.49 g. When bees were exposed daily to the formulation, a small increase in mortality occurred, and a significant difference was observed (p < 0.001) between t survival curves. During the acute toxicity exposure, there was a low mortality in the first days after exposure. Based on the results obtained, we assume that the MF has low acute toxicity and chronic using LC50 on A. mellifera.

Skin barrier repair efficacy and safety evaluation of an extract from Gardenia jasminoides J.Ellis

Gardenia jasminoides J.Ellis, a well-known traditional Chinese medicine, has been widely used in Asian countries for centuries. This study presented the skin barrier repair efficacy and safety evaluation of an extract from G. jasminoides. The results showed that GarPepair was primarily composed of geniposide and genipin-1-β-D-gentiobioside with concentrations of 3.39 and 1.03 mg/mL, respectively. GarPepair (1.25%, w/w), geniposide (50 μg/mL), and genipin-1-β-D-gentiobioside (50 μg/mL) showed no cytotoxicity but could significantly up-regulate mRNA level (82.5%, 54.4%, and 99.4%, respectively) and protein expression (68.7%, 57.1%, and 92.6%, respectively) of ZO-1 in HaCat cells induced by lipopolysaccharide. Moreover, GarPepair showed low acute toxicity on zebrafish with an IC50 value of 5.91% (w/w), indicating that GarPepair had high safety. In summary, we can conclude that GarPepair and its active ingredients (geniposide and genipin-1-β-D-gentiobioside) had significant skin barrier repair efficacy with high safety, making it suitable for use as an active substance in cosmetics.

Ethanol crude leaf extract of weeping fig (Ficus benjamina) causes mild hepatotoxicity in Sprague dawley rats

Weeping fig (Ficus benjaminaeaf extract has diverse medicinal properties but little is reported about its hepatotoxicity. This study determined the mean lethal dose (LD50) and investigated the effects of F. benjamina ethanol crude leaf extract on biochemical parameters and liver histology of Sprague Dawley rats. Twenty-nineemale rats weighing 133-204 g were used. The LD50 was determined with nine rats based on Lorke’s method. The experimental groups consisted of twenty rats, divided into four groups of five. Each group received treatment as follows: Control (feed and water only) and low, medium, and high doses (500, 1000, 1500 mg/kg respectively) of the extract orally for 21 days. All animals were weighed and sacrificed using Ketamine intra-peritoneal injection. Blood samples were collected for biochemical parameters of total bilirubin, conjugated bilirubin, aspartate aminotransferase (AST) alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Liver tissues were removed and processed by the formalin-fixed-paraffin wax-embedding method. The tissue blocks were sectioned and subjected to Hematoxylin/Eosin and Masson trichrome staining. The extract’s LD50 was &gt;5000 mg/kg. The rats’ body weights did not change statistically (p=0.985). Total bilirubin (p=0.003), conjugated bilirubin, AST, ALT, and ALP values (p=0.001) increased significantly. The AST high-doseroup had the highest fold increase (4.8). The liver histology showed mild sinusoidal dilation at 500 mg/kg. There was marked hemorrhage and fibrosis at medium and high doses. Although the extract had relatively low acute toxicity, 1000 and 1500 mg/kg doses were associated with mild hepatotoxicity characterized by veno-occlusion disease. The 500 mg/kg dose is safer for medicinal purposes.

Pinonic Acid Derivatives Containing Thiourea Motif: Promising Antifungal Lead Compound Targeting Cellular Barrier of Colletotrichum fructicola.

In order to explore novel antifungal lead compounds from plant essential oil, thirty-two pinonic acid derivatives containing thiourea groups were designed and synthesized using α-pinene as a raw material. One of these pinonic acid derivatives compound 3a exhibited noteworthy in vitro antifungal activity against Colletotrichum fructicola (EC50 = 9.22 mg/L), which was comparable to that of the positive control kresoxim-methyl (EC50 = 9.69 mg/L). Structure-activity relationship (SAR) studies demonstrated that the introduction of thiourea groups, F atoms, and Cl atoms into the structure of pinonic acid derivatives significantly improved their antifungal activity. The in vivo antifungal test revealed that compound 3a could effectively control pear anthracnose. It also proved that compound 3a showed low acute oral toxicity to honeybees (LD50 > 100 μg/bee) and low or no cytotoxicity to LO2 and HEK293 cell lines. The preliminary mechanism of action studies revealed that compound 3a caused mycelium deformity, increased cell membrane permeability, blocked the normal process of phospholipase C on the cell membrane, and reduced mycelium protein content. The results of molecular docking studies demonstrated the stable binding of compound 3a to phospholipase C and chitin synthetase. This study suggested that compound 3a could be used as a promising lead compound for the development of novel antifungal agents targeting the cellular barrier of C. fructicola.

Antimicrobial characteristics of endophytic Aspergillus terreus and acute oral toxicity analysis

BackgroundEndophytic fungi produce biologically robust metabolites suitable for diverse applications, which support the increasing exploration of these fungi. The study aimed to investigate the in vitro antimicrobial properties of the metabolites of endophytic fungus Aspergillus terreus which isolated from the leaves of Psidium guajava plants while the acute oral toxicity was assessed in vivo. ResultsA. terreus (OR125572) was successfully isolated for the first time from P. guajava. The ethyl acetate extract of A. terreus exhibited antibactericidal effects against Enterobacter aerogenes with a minimum inhibitory concentration of 18.75 mg/ml in contrast to 75.00 ± 0.0, 37.50, and 37.50 mg/ml, respectively against Staphylococcus aureus, Escherichia coli, and Bacillus sphaericus were 75.00 ± 0.0, 37.50, and 37.50 mg/ml, respectively. Analysis of the crude extract obtained from A. terreus by GC-MS revealed a total of 32 distinct compounds. The major components included 1,2-benzenedicarboxylic acid, di-iso-octyl ester; hexyl oxecan-2-one and phenol. The acute oral toxicity study found no symptoms of toxicity and no mortality until the 14th d, suggesting that the LD50 value of A. terreus extract might exceed 1 ml/kg. The group receiving 0.5 ml/kg of A. terreus extract experienced a 42.9% increase in body weight, while administration of varying dosages resulted in a significant reduction in MCV levels. There was also a significant increase in the proportion of monocytes across all treated groups. ConclusionsThe study demonstrated the potential of A. terreus as a source of antimicrobial and other bioactive compounds, with relatively low acute toxicity.How to cite: Shehabeldine AM, Abdelaziz AM, Abdel-Maksoud MA, et al. Antimicrobial characteristics of endophytic Aspergillus terreus and acute oral toxicity analysis. Electron J Biotechnol 2024;72. https://doi.org/10.1016/j.ejbt.2024.07.003.

Preclinical Evaluation of Soluble Epoxide Hydrolase Inhibitor AMHDU against Neuropathic Pain.

Inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic strategy for treating neuropathic pain. These inhibitors effectively reduce diabetic neuropathic pain and inflammation induced by Freund's adjuvant which makes them a suitable alternative to traditional opioids. This study showcased the notable analgesic effects of compound AMHDU (1,1'-(hexane-1,6-diyl)bis(3-((adamantan-1-yl)methyl)urea)) in both inflammatory and diabetic neuropathy models. While lacking anti-inflammatory properties in a paw edema model, AMHDU is comparable to celecoxib as an analgesic in 30 mg/kg dose administrated by intraperitoneal injection. In a diabetic tactile allodynia model, AMHDU showed a prominent analgesic activity in 10 mg/kg intraperitoneal dose (p < 0.05). The effect is comparable to that of gabapentin, but without the risk of dependence due to a different mechanism of action. Low acute oral toxicity (>2000 mg/kg) and a high therapeutic index makes AMHDU a promising candidate for further structure optimization and preclinical evaluation.

Impact of regional pest control on pesticide application in China from a perceived risks perspective

The Regional Pest Control program represents a strategic intervention aimed at optimizing pesticide use in crop production, thereby mitigating the environmental impact of agricultural non-point source pollution from pesticides and fostering the development of high-quality agriculture. This study examines the influence of farmers’ perceived risks on the adoption of the Regional Pest Control program and evaluates its effect on pesticide application across a nationally representative dataset from Heilongjiang, Jiangsu, Anhui, Hubei, and Sichuan provinces. To account for unobserved heterogeneity, an endogenous switching regression model was employed. The findings reveal that farmers’ perceived risks associated with the Regional Pest Control program significantly deter its adoption. Furthermore, the program has been effective not only in reducing the frequency of pesticide applications but also in increasing the usage of pesticides with lower acute toxicity levels. Notably, the impact of the Regional Pest Control program on pesticide application demonstrates considerable variation in accordance with farmers’ risk attitudes.

Evaluation of the in vivo acute toxicity and in vitro genotoxicity and mutagenicity of synthetic β-carboline alkaloids with selective cytotoxic activity against ovarian and breast cancer cell lines

The aim of this study was to evaluate the in vitro cytotoxic, genotoxic, and mutagenic potential and to determine the in silico ADME parameters of two synthetic β-carboline alkaloids developed as prototypes of antitumor agents (NQBio-06 and NQBio-21). Additionally, acute toxicity of the compounds was evaluated in mice. The results from the MTT assay showed that NQBio-06 presented higher cytotoxicity in the ovarian cancer cell line TOV-21 G (IC50 = 2.5 µM, selectivity index = 23.7). NQBio-21 presented an IC50 of 6.9 µM and a selectivity index of 14.5 against MDA-MB-231 breast cancer cells. Comet assay results showed that NQBio-06 did not induce chromosomal breaks in vitro, but NQBio-21 was genotoxic with and without metabolic activation (S9 fraction). Micronucleus assay showed that both compounds were mutagenic. In addition, metabolic activation enhanced this effect in vitro. The in silico predictions showed that the compounds met the criteria set by Lipinski's rules, had strong prediction for intestinal absorption, and were possible substrates for P-glycoprotein. The in vivo results demonstrated that both the compounds exhibited low acute toxicity. These results suggest that the mechanisms underlying the cytotoxicity of NQBio-06 and NQBio-21 are related to DNA damage induction and that the use of S9 enhanced these effects. In vivo analysis showed signs of toxicity after a single administration of the compounds in mice. These findings highlight the potential of β-carboline compounds as sources for the development of new anticancer chemotherapeutic agents.

Evaluation of Cytotoxicity and Acute Oral Toxicity of Saline Extract and Protein-Rich Fraction from Moringa oleifera Lam. Leaves.

Moringa oleifera Lam. (horseradish tree) leaves demonstrate high nutritional value, are rich in proteins, and are widely used in folk medicine and food. This study investigated the presence of secondary metabolites and antinutritional proteins in leaf extract (LE) and the protein-rich fraction (PRF) derived from M. oleifera leaves, as well as the cytotoxicity to human cells, hemolytic activity, and in vivo acute toxicity and genotoxicity in mice. The flavonoids rutin and vitexin as well as trypsin inhibitors and lectins were detected in LE and PRF. Neither sample demonstrated toxicity against human peripheral blood mononuclear cells and both showed low hemolytic action. In vivo, LE and PRF did not show antinutritional effects and caused no death. The hematological parameters of the animals in the treated group were similar to those of the control. A significant increase in the serum levels of alanine aminotransferase and a discrete leukocyte infiltration with cytoplasmic vacuolization of the hepatocytes in the liver were detected in LE-treated animals. The preparations were not genotoxic or mutagenic. This study shows that LE and PRF are not antinutritional agents and presented low acute toxicity and no genotoxicity or mutagenicity. The present study contributes to the determination of the safety of using M. oleifera leaf proteins.

Discovery of a novel Xanthone derivative P24 for anti-AD via targeting sTGFBR3

Soluble transforming growth factor beta receptor 3 (sTGFBR3) antagonist is a new focus in the research and development of Alzheimer's disease (AD) drugs. Our previous studies have identified sTGFBR3 as a promising new target for AD, with few targeted antagonists identified. In this study, we performed structural modeling of sTGFBR3 using AlphaFold2, followed by high-throughput virtual screening and surface plasmon resonance assays. which collectively identified Xanthone as potential compounds for targeting sTGFBR3. After optimizing the sTGFBR3-Xanthone complex using molecular dynamics (MD) simulations, we prepared a series of novel Xanthone derivatives and evaluated their anti-inflammatory activity, toxicity, and structure-activity relationship in BV2 cell model induced by lipopolysaccharides (LPS) or APP/PS1/tau mouse brain extract (BE). Several derivatives with the most potent anti-inflammatory activity were tested for blood-brain barrier permeability and sTGFBR3 affinity. Derivative P24, selected for its superior properties, was further evaluated in vitro. The results indicated that P24 increased the activation of TGF-β signaling and decreased the activation of IκBα/NF-κB signaling by targeting sTGFBR3, thereby regulating the inflammation-phagocytosis balance in microglia. Moreover, the low acute toxicity, long half-life, and low plasma clearance of P24 suggest that it can be sustained in vivo. This property may render P24 a more effective treatment modality for chronic diseases, particularly AD. The study demonstrates P24 serve as potential novel candidates for the treatment of AD via antagonizing sTGFBR3.

Stepwise Structural Simplification of the Dihydroxyanthraquinone Moiety of a Multitarget Rhein-Based Anti-Alzheimer Lead to Improve Drug Metabolism and Pharmacokinetic Properties.

Multitarget compounds have emerged as promising drug candidates to cope with complex multifactorial diseases, like Alzheimer's disease (AD). Most multitarget compounds are designed by linking two pharmacophores through a tether chain (linked hybrids), which results in rather large molecules that are particularly useful to hit targets with large binding cavities, but at the expense of suffering from suboptimal physicochemical/pharmacokinetic properties. Molecular size reduction by removal of superfluous structural elements while retaining the key pharmacophoric motifs may represent a compromise solution to achieve both multitargeting and favorable physicochemical/PK properties. Here, we report the stepwise structural simplification of the dihydroxyanthraquinone moiety of a rhein-huprine hybrid lead by hydroxy group removal-ring contraction-ring opening-ring removal, which has led to new analogs that retain or surpass the potency of the lead on its multiple AD targets while exhibiting more favorable drug metabolism and pharmacokinetic (DMPK) properties and safety profile. In particular, the most simplified acetophenone analog displays dual nanomolar inhibition of human acetylcholinesterase and butyrylcholinesterase (IC50 = 6 nM and 13 nM, respectively), moderately potent inhibition of human BACE-1 (48% inhibition at 15 µM) and Aβ42 and tau aggregation (73% and 68% inhibition, respectively, at 10 µM), favorable in vitro brain permeation, higher aqueous solubility (18 µM) and plasma stability (100/96/86% remaining in human/mouse/rat plasma after 6 h incubation), and lower acute toxicity in a model organism (zebrafish embryos; LC50 >> 100 µM) than the initial lead, thereby confirming the successful lead optimization by structural simplification.

Antinociceptive and anti-inflammatory activities of Ayapana triplinervis essential oil rich in thymohydroquinone dimethyl ether from Brazil.

Ayapana triplinervis (M.Vahl) R.M.King & H.Rob. (Asteraceae), popularly known as japana, is a tropical, aromatic subshrub widely used as tea to combat some diseases. The essential oil was obtained from the leaves by hydrodistillation (3h), and the chemical composition was analyzed by gas chromatography coupled to mass spectrometry. For in vivo assays, Mus musculus/Swiss mice were used to evaluate oral acute toxicological (at dose of 2000mg/kg); peripheral and central analgesic for abdominal contortion (doses of 6.25, 12.5, 25, 50 and 100mg/kg), hot plate test (12.5, 25, 50, and 100mg/kg) and formalin (25, 50 and 100mg/kg); open field test (100mg/kg); and anti-inflammatory by ear swelling induced by xylene (6.25,12.5, 25, 50, and 100mg/kg). The yield of A. triplinervis essential oil (AtEO) was 4.6%, and the oxygenated monoterpene 2,5-dimethoxy-p-cymene was the major compound in this study (63.6%). AtEO at a dose of 2,000mg/kg orally did not change the behavior patterns or mortality of the animals; liver and kidney biochemical levels were similar to the control group, indicating no liver and kidney toxicity. Moreover, AtEO, at doses of 6.25, 12.5, 25, 50, and 100mg/kg, reduced abdominal contortions by 21%, 54%, 91%, 58%, and 55%, respectively. In the hot plate test, AtEO showed a significant increase in latency time in the 60-min interval at doses of 25mg/kg (11.3 ± 3.3s) and 100mg/kg (11.9 ± 0.9s). In the first phase of the formalin test, AtEO decreased paw licking time at doses of 25, 50, and 100mg/kg, with inhibition of 22%, 38%, and 83%; in the second phase, the same doses, decreased licking time with inhibition of 24%, 34%, and 76%. AtEO did not present a significant change in the spontaneous locomotor activity of the animals. Doses of 6.25, 12.5, 25, 50, and 100mg/kg significantly reduced ear edema induced by topical application of xylene with percentages of 40%, 39%, 54%, 45%, and 45%, respectively. So, AtEO demonstrated low acute oral toxicity and exhibited significant antinociceptive and anti-inflammatory actions, consistent with the use of A. triplinervis in traditional medicine.

Evaluation of the Potentials of Tobacco Waste Extract as Wood Preservatives against Wood Decay Fungi

Utilizing conventional wood preservatives poses potential risks to ecosystems and human health. Therefore, the wood protection industry must develop alternatives that are both efficient and environmentally friendly. In this paper, industrial tobacco waste extracts were used as eco-friendly wood preservatives against wood decay fungi. Three major constituents in the extracts were identified via gas chromatography-mass spectrometry (GC-MS) and included nicotine, neophytadiene, and 2,7,11-cembratriene-4,6-diol. The antifungal activities of waste tobacco extracts and these three major constituents against wood decay fungi were tested. At a concentration of 40 mg/mL, the tobacco waste extract treated with 50% ethanol significantly inhibited the activity of wood decay fungi. This was because the extract contained nicotine as the primary active component and neophytadiene as a synergistic active component. Wood decay resistance tests were conducted on Pinus yunnanensis and Hevea brasiliensis treated with a 50% ethanol extract of tobacco waste at a concentration of 40 mg/mL. The mass losses of Pinus yunnanensis exposed to G. trabeum and T. versicolor were 4.11% and 5.03%, respectively, while the mass losses in Hevea brasiliensis exposed to G. trabeum and T. versicolor were 7.85% and 9.85%, respectively, which were classified as highly resistant. The acute ecotoxicity of the tobacco waste extract was assessed using a kinetic luminescent bacteria test with Aliivibrio fischeri, which revealed significantly lower acute toxicity than a commercial copper-based wood preservative. This study offers insights into high-value utilization of tobacco waste and advancement of natural wood preservatives.

Spray-dried microparticles of turmeric extract for improved delivery and low toxicity

This study aimed to enhance the delivery of turmeric by encapsulating its extract within microparticles using chitosan and mannitol through the spray drying technique and to assess their acute oral toxicity. The resulting microparticles were spherical, with an average diameter of 4 microns, and comprised 17% curcuminoids and 4% ar-turmerone. In vitro studies demonstrated that these microparticles had a higher release rate of curcuminoids compared to raw turmeric extract and preserved antioxidant activity. In the acute toxicity study, conducted in Wistar rats with a single dose of 2,000 mg/kg, no acute toxic symptoms were observed. According to the Globally Harmonized System of Classification and Labeling of Chemicals, the microparticles were categorized as having relatively low acute toxicity (category 5). These findings support the potential utility of the microparticles in dietary supplements and pharmaceutical applications due to their effective delivery properties and safety profile.

X-Ray-Sensitizers: Organic Pharmaceutical Drug Intermediates Activated Directly by X-Rays to Efficiently Populate Triplet Excitons for Cancer Treatment

Radiotherapy is an important treatment for cancer, but it is associated with major side effects due to the high dose of radiation (generally more than 50 Gy). Because radiation’s low acute and late toxicity, many tumors are treated with fractionated radiation in small doses (< 2 Gy). Scintillator X-ray-induced photodynamic therapy is an efficient methodology for cancer management that employs small doses of X-ray irradiation (< 2 Gy) in a complex process. Here we screened pharmaceutical drug intermediates that are derivatives of thioxanthone (TX) and investigated TX-derived organic pharmaceutical molecules that efficiently undergo X-ray-sensitization to populate triplet excitons (singlet oxygen) for cancer therapy when exposed to low-dose X-ray irradiation. By modifying alkoxy side chain substitutions at the 2-position to tune the molecular packing and intermolecular interactions, the fluorescence and room-temperature phosphorescence of a series of TX derivatives were assessed under X-ray irradiation. The ability of these derivatives to generate singlet oxygen and their potential for treating tumors provide new opportunities for developing organic molecules with simple chemical structures, in which large numbers of triplets can be populated directly under ultralow-dose X-ray irradiation.

Toxic effect of mussel Mytilus galloprovincialis exposed to Ag–TiO2 and ZnTi2O4–TiO2 bicomponent nanoparticles

Nanoparticles (NPs) are widely used in various fields, including antifouling paints for ships and industrial structures submerged in water. The potential impact of NPs on aquatic organisms, particularly their potential toxicity, is a significant concern, as their negative impact has been relatively poorly studied. In this study, we evaluated the effect of different concentrations of bimetallic Ag–TiO₂ and ZnTi₂O₄-TiO₂ NPs, which could potentially be used in antifouling coatings, on the hemocytes of the Mediterranean mussel Mytilus galloprovincialis. Hemocytes were exposed to NPs at concentrations of 0.1–1 mg/L for 1 and 2 h, and the production of reactive oxygen species (ROS), levels of DNA damage, and number of dead cells were measured. Exposure to Ag–TiO₂ NPs at 1 mg/L concentration for 1 h suppressed ROS production in hemocytes and reduced the relative number of agranulocytes in cell suspensions, without inducing DNA damage or cell death. Exposure to ZnTi2O4–TiO2 NPs did not cause changes in the ratio of granulocytes to agranulocytes in suspensions, nor did it affect other functional parameters of hemocytes. However, after a 2 h exposure period, ZnTi2O4–TiO2 NPs (1 mg/L) significantly reduced the production of ROS by hemocytes. These findings suggest that Ag–TiO2 and ZnTi2O4–TiO2 NPs have low acute toxicity for marine bivalves.

Breast Cancer Adjuvant Radiotherapy in Up-Front to Chemotherapy: Is There a Worthwhile Benefit? A Preliminary Report.

We administered a new breast cancer (BC) adjuvant therapy sequence that delivered postoperative radiotherapy (PORT) before chemotherapy (CT). Our aim was to assess the gain in time to start PORT and the G2-G3 acute-subacute toxicity rate of whole breast adjuvant hypofractionated radiotherapy (AH-RT) administered up-front to the third-generation adjuvant CT (A-CT) in high-risk nodal positive BC in a preliminary report at 2 years. This retrospective study analysed the duration of treatment and safety of AH-RT administered up-front to A-CT in high-risk nodal positive BC patients (pts). Data on 45 pts treated between 2022-2023 were collected. All pts underwent the third-generation A-CT after AH-RT 15-5 fractions with or without a boost. Acute toxicity was scored according to CTCAE v5.0 for skin, pulmonary, and cardiac adverse events. Univariate and multivariate analyses were conducted to assess significant prognosticators for skin/lung/heart acute toxicities in the AH-RT 5-15 fractions arms and CT (p < 0.005). A reduction in the time to PORT initiation and overall adjuvant treatment time was recorded. RT was initiated 5 median weeks after surgery, and A-CT was performed 9 median weeks after surgery. The median duration of the entire adjuvant treatment was 35 weeks after surgery. At 6 months mean follow-up, no significant differences in G2-G3 toxicity were noted between the different hypofractionated RT arms, irrespective of the CT schedules, irradiated volumes, or boost (SIB or sequential) in univariate and multivariate analyses. In the multivariate analysis, no significant effects in CT schedules and AH-RT 5-15 arms for skin/lung acute toxicities (p = 0.077 and p = 0.68; 0.67 and 0.87, respectively) were recorded. As a new PORT approach in BC, AH-RT up-front to the third-generation A-CT appeared safe with a low acute toxicity profile, providing an advantage in shortening the time from surgery to PORT initiation and the overall adjuvant treatment time.

Evaluation of the acute and sub-acute toxicity of the standardized extract of Avicennia officinalis L. in mice

Avicennia officinalis L. (AOL) has shown promise for its anti-inflammatory, anti-cancer, and antioxidant properties. However, there is no research on the toxicity of this plant in Vietnam. The acute and sub-acute toxicology study proved that AOL leaf extracts are practically non-toxic in normal mice. Acute toxicity assessment was conducted with single oral doses of AOL extract (2500, 3100, 4100, and 5000 mg/kg). In sub-acute toxicity, mice were administered daily oral doses of AOL extract (200 and 400 mg/kg) for 28 days. Blood was collected from the heart, liver, and kidneys for further analysis. The comprehensive results revealed an oral median lethal dose (LD50) exceeding 5000 mg/kg, indicating low acute toxicity. A sub-acute study (200 and 400 mg/kg/day) showed no deaths or weight gain. At both doses, the standardized AOL extracts decreased serum aspartate transaminase activity. Administration of the 200 mg/kg group significantly increased blood urea levels; however, histological examination of mouse kidneys in this group revealed no signal of damage. Histological examination of mouse livers revealed mild degeneration, possibly due to the use of adult mice and potentially unrelated to the extract. This study emphasizes AOL's potential for further pharmacological testing based on its low acute toxicity and promising results.