Poisoning Research Articles

Leaching hazards of tire wear particles in hydrothermal treatment of sludge: Exploring molecular composition, transformation mechanism, and ecological effects of tire wear particle-derived compounds

Tire wear particles (TWPs) are considered a significant contributor of microplastics (MPs) in the sludge during heavy rainfall events. Numerous studies have shown that hydrothermal treatment (HT) of sludge can accelerate the leaching of MP-derived compound into hydrothermal liquid, thus impairing the performance of subsequent anaerobic digestion and the quality of the hydrothermal liquid fertilizer. However, the leaching behavior of TWPs in the HT of sludge remains inadequately explored. This study examined the molecular composition of TWP-derived compounds and transformation pathways of representative tire-related additives under different hydrothermal temperatures using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with mass difference analysis. The acute toxicity and phytotoxicity of TWP leachates were assessed using Vibrio qinghaiensis Q67 and rice hydroponics experiments. The results indicated that elevating the hydrothermal temperature not only amplified the leaching behavior of TWPs but also enhanced the chemical complexity of the TWP leachate. Utilizing both suspect and non-target screenings, a total of 144 compounds were identified as additives, including N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine (6-PPD), hexa(methoxymethyl)melamine (HMMM), dibutyl phthalate (DBP). These additives underwent various reactions, such as desaturation, acetylation, and other reactions, leading to the formation of different transformation products (TPs). Moreover, certain additives, including caprolactam and 2,2,6,6-tetramethyl-4-piperidinol, demonstrated the potential to form conjugate products with amino acids or Maillard products. Meanwhile, TWP-derived compounds showed significant acute toxicity and detrimental effects on plant growth. This study systematically investigated the environmental fate of TWPs and their derived compounds during the HT of sludge, offering novel insights into the intricate interactions between the micropollutants and dissolved organic matter (DOM) in sludge.

Targeted Development of Pyrazoline Derivatives for Neurological Disorders: A Review

AbstractPyrazolines are preferred to be stable heterocycles in medication development. It has been established from previous research that the 2‐pyrazolone scaffold is a common pattern that can be found in many pharmacologically significant therapeutic compounds. They are said to have a wide range of biological actions and have been thoroughly investigated by the scientific community. 2‐pyrazoline has been used as an intriguing pharmacophore to create novel compounds with enhanced potency, less toxicity, and the necessary pharmacokinetic profile to treat unprecedented diseases and global drug resistance. Experiments done by docking confirmed the hypothesized neuropharmacological mode of action and demonstrated a strong affinity towards the monoamine oxidase, β‐amyloid plaques, and AChE. Furthermore, additional computational pharmacokinetic assessments signify that it may not have any significant risk of carcinogenic effects, neurotoxic effects, reproductive intoxication, acute toxicity, mutagenicity, or irritations suggesting their possible utility in depressive, convulsions, and anxiety disorders. This discussion outlines a reliable approach for medicinal chemists to develop pyrazolines for the establishment of neurodegenerative research as well as future research programs on neurodegenerative disorders.

Pharmacodynamic and Toxicity Studies of 6-Isopropyldithio-2'-guanosine Analogs in Acute T-Lymphoblastic Leukemia.

(1) Background: The research group has developed a new small molecule, 6-Isopropyldithio-2'-deoxyguanosine analogs-YLS004, which has been shown to be the most sensitive in acute T-lymphoblastic leukemia cells. Moreover, it was found that the structure of Nelarabine, a drug used to treat acute T-lymphoblastic leukemia, is highly similar to that of YLS004. Consequently, the structure of YLS004 was altered to produce a new small molecule inhibitor for this study, named YLS010. (2) Results: YLS010 has exhibited potent anti-tumor effects by inducing cell apoptosis and ferroptosis. A dose gradient was designed for in vivo experiments based on tentative estimates of the toxicity dose using acute toxicity in mice and long-term toxicity in rats. The study found that YLS010 at a dose of 8 mg/kg prolonged the survival of late-stage acute T-lymphoblastic leukemia mice in the mouse model study. (3) Conclusions: YLS010 has demonstrated specific killing effects against acute T-lymphoblastic leukemia both in vivo and in vitro. Preclinical studies of YLS010 offer a new opportunity for the treatment of patients with acute T-lymphoblastic leukemia in clinical settings.

Health Effects of Heavy Metal Contamination in Drinking Water

Water is essential for life, be it the life of animals, plants or human beings. It’s our prime duty to protect, manage and preserve the quality of water. Uncontrolled anthropogenic activities have resulted in contamination of fresh water resources thereby affecting the health of living beings. Rampant industrialization is a major environmental problem on the global scale for the pollution of fresh water with toxic effluents containing heavy metals. Contamination of surface water by heavy metals is the greatest quality issues because of their toxic nature, increased release and negative impact on the health of human beings. Water-borne diseases remain one of the major health concerns in the world. Heavy metals are individual metals and metal compounds that can impact human health. Exposure of humans to metals such as antimony, arsenic, barium, cadmium, chromium, cobalt, copper, iron, lead, manganese, mercury, nickel, selenium, silver, tin, zinc, etc results in chronic and acute toxicities. The toxicity of heavy metals depends on their concentration, period of exposure and route of exposure. Humans are exposed to heavy metals either by inhalation from the atmosphere, intake through drinking water, or by ingestion through the skin by dermal contact. The present review describes the analysis of ‘heavy metal contamination in drinking water’ with reference to definition, sources, health effects on humans and preventive measures. This study suggests that, the best way to get rid of heavy metal contamination in drinking water is to remove toxic heavy metals by using the best water purification system. Also, the ground water resources must be monitored for quality assessment, source identification and bioremediation of heavy metals.

Preclinical safety evaluation of the ethanolic extract from campomanesia guazumifolia (cambess.) O. Berg fruits peels in rats

The toxicological potential of the ethanolic extract from Campomanesia guazumifolia (EECG), a species traditionally recognised for its antidiabetic, anti-inflammatory and hypercholesterolemic properties, was investigated in acute and subacute toxicity models in rats. In the acute toxicity test, 2000 mg/kg of EECG was administered orally in female rats, while male and female rats received 250, 500 or 750 mg/kg of EECG for the subacute toxicity test. No evidence of toxicity was observed in the animals acutely exposed, indicating that the LD50 is above 2000 mg/kg. However, repeated exposure to this extract resulted in alterations in important biochemical parameters indicative of hepatic and renal toxicity, including AST, ALT, creatinine, urea, and cholesterol. Additionally, some hematological parameters were also changed by the treatment. EECG demonstrated low toxicological potential. Nevertheless, given the observed changes in liver and kidney enzymes, further investigations into the protective effects of this extract following repeated administration are warranted.

Acute Toxicity Testing of Pink Salmon (Oncorhynchus gorbuscha) with the Tire Rubber-Derived Chemical 6PPD-Quinone.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-quinone) is a widespread contaminant of emerging concern resulting from oxidation of 6PPD, which is an antidegradant substance added to tires. The recent identification of 6PPD-quinone as the cause of acute mortality in coho salmon has quickly motivated studies on 6PPD-quinone toxicity to other species. Subsequent findings have shown that 6PPD-quinone toxicity is highly species specific. Closely related species can differ widely in response to 6PPD-quinone from extremely sensitive to tolerant. Hence toxicity testing is currently the only way to establish whether a species exhibits 6PPD-quinone toxicity. We investigated the acute toxicity of 6PPD-quinone in pink salmon alevins (sac fry). This species has is the only Pacific salmon that so far has not been tested for 6PPD-quinone sensitivity. Fish were exposed in static water in eight treatments with initial concentrations ranging from 0.1 to 12.8 μg/L. Fish were observed for 48 h, and changes in concentrations of 6PPD-quinone were monitored throughout the experiment. No mortalities or substantial changes in behavior were recorded. Environ Toxicol Chem 2024;00:1-7. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Phytochemistry and Evaluation of Acute Toxicity of Aqueous and Hydroethanolic Extracts of Pavetta corymbosa Leaves (Rubiaceae)

Pavetta corymbosa (Rubiaceae) is a plant widely known in sub-Saharan Africa in the field of traditional medicine. It is used empirically against certain pathologies such as malaria, diabetes, hemorrhages and typhoid fever. However, there is no scientific data on its phytochemical and biological profile, so this study was carried out to research the chemical groups contained in the leaves of this plant and determine the toxicological parameters which would justify its use in traditional medicine. Several standard characterization methods were used for phytochemical screening of aqueous and hydroethanolic extracts of Pavetta corymbosa leaves. The study of the acute toxicity of the two types of extracts from the leaves of this plant was carried out according to the OECD guideline 423 using Wistar rats. Phytochemical screening indicated the existence of polyphenols, saponosides, quinones, flavonoids, polyterpenes and sterols in the two types of extracts of this plant, which would justify its biological and pharmacological effects. The study of the acute toxicity of these two types of extracts, administered intraperitoneally to Wistar rats, showed no mortality of the rats. These toxicological results allow us to qualify the leaves of Pavetta corymbosa as being non-toxic, hence the interest in its use in traditional medicine against certain pathologies.

ProTox 3.0: a webserver for the prediction of toxicity of chemicals.

Interaction with chemicals, present in drugs, food, environments, and consumer goods, is an integral part of our everyday life. However, depending on the amount and duration, such interactions can also result in adverse effects. With the increase in computational methods, the in silico methods can offer significant benefits to both regulatory needs and requirements for risk assessments and the pharmaceutical industry to assess the safety profile of a chemical. Here, we present ProTox3.0, which incorporates molecular similarity and machine-learning models for the prediction of 61 toxicity endpoints such as acute toxicity, organ toxicity, clinical toxicity, molecular-initiating events (MOE), adverse outcomes (Tox21) pathways, several other toxicological endpoints and toxicity off-targets. All the ProTox 3.0 models are validated on independent external sets and have shown strong performance. ProTox envisages itself as a complete, freely available computational platform for in silico toxicity prediction for toxicologists, regulatory agencies, computational chemists, and medicinal chemists. The ProTox 3.0 webserver is free and open to all users, and there is no login requirement and can be accessed via https://tox.charite.de. The web server takes a 2D chemical structure as input and reports the toxicological profile of the compound for each endpoint with a confidence score and overall toxicity radar plot and network plot.

Toxicity study and ameliorative effects of the aqueous leaf extract of Lecanoidiscus cupanioides Planch (ex. Benth) on the stress-induced ulcer

Lecaniodiscus cupanioides Planch (ex. Benth) is effective in treating burns, fevers, and inflammatory conditions. This study investigates the toxicity effects of the aqueous leaf extract (ALE) of L. cupanioides and its effect on stress-induced ulcers in animal models. The plant was collected and a 1:30 (g/ml) plant powder/solvent ratio was extracted using an ultrasonic bath at 50 °C for 45 min. Up-and-down procedure was used for acute toxicity. During subacute toxicity testing, a total of 20 mice were divided into four groups of five animals each. While group 1 served as control, groups 2, 3, and 4 received 250, 500, and 1000 mg/kg of the extract daily for 21 days. On day 22nd, animals were sacrificed and samples were collected for hematology, biochemical, and histological analyses. In the stress-induced ulcer activity, male albino mice were randomly separated into 5 groups of 5 animals, treated with the test drug, and then dissected after being stressed using the water immersion model. LD50 was > 5000 mg/kg, and in biochemical examination, there was a significant decrease in the ALP level at medium and high doses (p value < 0.05) and non-significant alterations in the values of urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), body weight and hematology parameters (p > 0.05). The histology results showed no evidence of liver and kidney toxicity. In conclusion, aqueous leaf extract of L. cupanioides was safe following a single dose (at 5000 mg/kg) and following repeated doses for 21 days (at 250, 500, and 1000 mg/kg). This study demonstrated that the extract had a significant effect on stress-induced ulcers at various dose levels when compared to the control (native, negative control, and omeprazole). The animals treated with 200mg/kg and 400mg/kg of the extract showed a significant increase in ulcer score, ulcer index, ulcer severity, and total acidity (p < 0.05). The ulcer protection ability of the aqueous plant extract was dose-dependent.

Comprehensive characterization of organics in oil sands process water in constructed mesocosms utilizing multiple analytical methods

This study aims to provide a thorough characterization of dissolved organics in oil sands process water (OSPW) in field-based aquatic mesocosms at both molecular and bulk measurement levels using multiple analytical methods. In a 3-year outdoor mesocosm experiment, the analysis of naphthenic acid (NA) species was conducted using ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOFMS). The results revealed the removal of both total NAs (38% and 35%) and classical NAs (O2–NAs, 58% and 49%) in undiluted and half-diluted OSPW, respectively. The increased ratios of oxidized NAs (O3–O6 NAs) to classical NAs suggested a transformation trend. The results also indicated that O2–NAs with higher carbon number and lower double bond equivalent (DBE) were more easily degraded in the mesocosm systems. Biomimetic extraction using solid-phase microextraction (BE-SPME) measurement displayed 26% (undiluted OSPW) and 30% (half-diluted OSPW) decrease in total bioavailable organics over 3 years. Naphthenic acids fraction compounds (NAFCs) obtained by liquid-liquid extraction (LLE) were also determined using Fourier transform infrared spectroscopy (FTIR). Reduction in acute toxicity for undiluted (43%) and half-diluted (26%) OSPW was observed over 3 years, which are well correlated with the decreases of NAs and BE-SPME concentrations. Moreover, BE-SPME values were found to be linearly correlated with total NAs concentrations (r = 0.96) and NAFCs (r = 0.96). Additionally, the linear relationships of individual O2–O6 NA species and BE-SPME concentrations unveiled the changes in the relative abundances of O2–O6 NA species in total bioavailable organics over time in the mesocosms. The present study has provided comprehensive insights by integrating various analytical methods, contributing valuable information for assessing the effectiveness of aquatic mesocosm systems in studying the temporal changes of organics in OSPW.

Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation

A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC50 value of 3.94 ± 0.17 µmol L−1 (NCI-H1299), 3.16 ± 0.11 µmol L−1 (A549), and 1.83 ± 0.13 µmol L−1 (NCI-H1437) for 7a, and an IC50 value of 3.84 ± 0.22 µmol L−1 (NCI-H1299), 3.86 ± 0.38 µmol L−1 (A549), and 1.69 ± 0.25 µmol L−1 (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung cancer.

Ecotoxicological strategies employing biochemical markers and organisms to monitor the efficacy of malathion photolysis treatment

The objective of this study was to assess the photolysis-mediated degradation of malathion in standard and commercial formulations, and to determine the toxicity of these degraded formulations. Degradation tests were carried out with 500 μg L−1 of malathion and repeated three times. The initial and residual toxicity was assessed by using Lactuca sativa seeds for phytotoxicity, Stegomyia aegypti larvae for acute toxicity, and Stegomyia aegypti mosquitoes (cultivated from the larval stage until emergence as mosquitoes) to evaluate the biochemical markers of sublethal concentrations. For the standard formulations the photolytic process efficiently reduced the initial concentration of malathion to levels below the regulatory limits however, the formation of byproducts was revealed by chromatography, which allowed for a more complete proposal of photolytic-mediated malathion degradation route. The degraded formulations inhibited the growth of L. sativa seeds, while only the untreated formulations showed larvicidal activity and mortality. Both formulations slightly inhibited acetylcholinesterase activity in S. aegypti mosquitoes, while the standard formulation decreased and the commercial formulation increased glutathione S-transferase activity. However, there were no significant differences for superoxide dismutase, esterase-α, esterase-β and lipid peroxidation. These findings indicate that in the absence of the target compound, the presence of byproducts can alter the enzymatic activity. In general, photolysis effectively degrade malathion lower than the legislation values; however, longer treatment times must be evaluated for the commercial formulation.

Synthesis, in vitro Anti-HIV-1RT evaluation, molecular modeling, DFT and acute oral toxicity studies of some benzotriazole derivatives

This study synthesized and evaluated a series of benzotriazole derivatives denoted 3(a-j) and 6(a-j) for their anti-HIV-1 RT activities compared to the standard drug efavirenz. Notably, compound 3 h, followed closely by 6 h, exhibited significant anti-HIV-1 RT efficacy relative to the standard drug. In vivo oral toxicity studies were conducted for the most active compound 3 h, confirming its nontoxic nature to ascertain the safety profile. By employing molecular docking techniques, we explored the potential interactions between the synthesized compounds (ligands) and a target biomolecule (protein)(PDB ID 1RT2) at the molecular level. We undertook the molecular dynamics study of 3 h, the most active compound, within the active binding pocket of the cocrystallized structure of HIV-1 RT (PDB ID 1RT2). We aimed to learn more about how biomolecular systems behave, interact, and change at the atomic or molecular level over time. Finally, the DFT-derived HOMO and LUMO orbitals, as well as analysis of the molecular electrostatic potential map, aid in discerning the reactivity characteristics of our molecule.

Optimization and characterization of pyraclostrobin nanoemulsion for pesticide delivery: Improving activity, reducing toxicity, and protecting ecological environment

Nanoemulsion provides an effective way for the efficient, safe, and environmentally friendly use of pesticides. In this study, the influence of different type emulsifiers on the formation and stability of nanoemulsion were tested and an optimal pyraclostrobin nanoemulsion with long-term stability was obtained. Pyraclostrobin (2.5 %), #602 (phenylethyl phenol polyoxyethylene ether, 6 %), and #600 P (tristyryl- phenol polyoxyethylene ether phosphate, 2 %) were dissolved in methyl benzoate (2.5 %) and co-emulsifier ethanol (20 %) with deionized water replenished to 100 %. Compared with microemulsion (ME), the nanoemulsion using a lower dosage of emulsifier kept the system stable for a long time, reducing pollution of the environment. Compared with the commercial ME and suspension concentrate (SC), the nanoemulsion had a lower contact angle and surface tension, and higher maximum retention. In addition, adding 0.01 % AEO-3 (dodecyl alcohol polyol ethylene ether) to the dilution of nanoemulsion can significantly improve the target deposition of the nanoemulsion and improve the utilization rate of the pesticide. Besides, the use of methyl benzoate, an environmentally friendly solvent, resulted in the nanoemulsion with high bactericidal activity and low acute toxicity to zebrafish, thus reducing the environmental pollution of such chemicals.

Research progress in emergency assessment of acute poisoning

Acute poisoning represents a prevalent critical illness jeopardizing patient survival. Early, precise assessment of the condition and subsequent appropriate therapeutic intervention are pivotal in enhancing treatment success rates. Currently, a standardized approach to evaluating the severity of acute poisoning is lacking. Various scoring systems, including Poisoning Severity Score (PSS) , Modified Early Warning Score (MEWS) , and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) , offer valuable insights into acute poisoning assessment. Nevertheless, the distinct attributes of each scoring system constrain their broad clinical utility. Confronted with the intricate clinical demands of acute poisoning, the adoption of staged and dynamic assessment strategies is imperative to ascertain the condition of acute poisoning patients with greater accuracy.

Visible-light-induced degradation of rhodamine B by double Z-scheme magnetic ATP-g-C3N4/SnFe2O4/Bi2WO6 heterojunctions: Performance and mechanism

A magnetic ternary double Z-scheme ATP-g-C3N4/SnFe2O4/Bi2WO6 (AG/SFO/BWO) heterojunction was prepared by a simple and green hydrothermal process, which was successfully used in the dye degradation. AG/7.5 %SFO/BWO catalyst demonstrated outstanding visible-light-induced degradation, achieving an impressive 96.72 % degradation of rhodamine B (RhB) in 2 h. Compared with Bi2WO6 (BWO) and SnFe2O4/Bi2WO6 (SFO/BWO), the degradation efficacy was increased about 1.65 and 1.16 times, respectively. After being used for five batches, the degradation rate of RhB remained over 90 %. Moreover, AG/7.5 %SFO/BWO showcased remarkable efficacy in degrading methylene blue (MB), Congo red (CR), and tetracycline (TC). Bacterial toxicity test indicated the toxicity of dyes was rapidly decreased in 24 h. Physicochemical properties and morphological characteristics of the prepared photocatalysts were investigated by various methods, including XRD, FTIR, XPS, SEM, TEM, BET, VSM, UV–vis, and EIS. AG/7.5 %SFO/BWO, utilizing a dual-Z scheme pathway, efficiently absorbed broad light, yielding multiple active agents, primarily hole (h+) and superoxide radical •O2−. The double Z-scheme heterojunction structure enhanced the electron-hole separation and ensured a stable photochemical environment. UPLC-HRMS was used to identify intermediates during the RhB degradation. Its degradation pathway and catalytic mechanism were illustrated systematically. The bio-toxicity (acute toxicity, developmental toxicity, and mutagenicity) of the intermediates was also evaluated by T.E.S.T.

Binge alcohol induces NRF2-related antioxidant response in the skeletal muscle of female mice

BackgroundChronic alcohol enhances oxidative stress, but the temporal response of antioxidant genes in skeletal muscle following a binge drinking episode remains unknown. MethodsExperiment 1: C57BL/6Hsd female mice received an IP injection of saline (CON; n = 39) or ethanol (ETOH; n = 39) (5 g/kg). Gastrocnemius muscles were collected from baseline (untreated; n = 3), CON (n = 3), and ETOH (n = 3) mice every 4 h for 48 h. Experiment 2: Gastrocnemius muscles were collected from control-fed (CON-FED; n = 17), control-fasted (CON-FAST; n = 18), or alcohol-fed (ETOH-FED; n = 18) mice every 4hrs for 20hrs after saline or ethanol (5 g/kg). ResultsEtOH enhanced Superoxide dismutase 1 (Sod1) and NADPH Oxidase 4 (Nox4) from 24 to 48hr after the binge, while Sod2 and Nox2 were suppressed. Nuclear factor erythroid-derived 2-like 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) increased 12hrs after intoxication. Cytochrome P450 oxidoreductase (Por), Heme oxygenase 1 (Ho1), Peroxiredoxin 6 (Prdx6), Glutamate-cysteine ligase catalytic subunit (Gclc), Glutamate-cysteine ligase modifier subunit (Gclm), and Glutathione-disulfide reductase (Gsr) were increased by ETOH starting 12–16hrs post-binge. Fasting had similar effects on Nrf2 compared to alcohol, but downstream targets of NRF2, including Por, Ho1, Gclc, and Gclm, were differentially altered with fasting and EtOH. ConclusionThese data suggest that acute alcohol intoxication induced markers of oxidative stress and antioxidant signaling through the NRF2 pathway and that there were effects of alcohol independent of a possible decrease in food intake caused by binge intoxication.

Safety, Analgesic, and Anti-Inflammatory Effects of Aqueous and Methanolic Leaf Extracts of Hypericum revolutum subsp. keniense

In light of the enduring obstacles encountered in analgesia and anti-inflammatory therapeutics despite the strides made in contemporary medical sciences, the quest for alternative efficacious strategies is an imperative pursuit. Thus, this study investigated the safety profiles, as well as the analgesic and anti-inflammatory attributes, of aqueous and methanolic leaf extracts derived from Hypericum revolutum subsp. keniense—a botanical entity entrenched in historical ethnomedicinal practices in the Kenyan context. The assessment of acute oral toxicity of these extracts was conducted in accordance with the Up- and-Down method advocated by the Organisation for Economic Cooperation and Development (OECD), utilizing Swiss albino mice as the experimental subjects. Subsequent investigation entailed the evaluation of antinociceptive and anti-inflammatory properties employing the acetic acid-induced writhing and carrageenan-induced paw oedema methodologies, respectively, in the same murine model. The findings of this study evince the safety of both aqueous and methanolic extracts, with LD50 values surpassing 2000 mg/kg body weight and the absence of discernible signs of toxicity. Furthermore, a notable dose-dependent (P<0.05) manifestation of analgesic effects was observed for both extracts, with the aqueous variant demonstrating heightened potency compared to its methanolic counterpart (P<0.05). Moreover, the anti-inflammatory efficacy escalated significantly with escalating extract doses and prolonged treatment duration (P<0.05), wherein the aqueous extract showcased superior effectiveness vis- à-vis the methanolic extract across all dosage regimens and temporal checkpoints (P<0.05). Therefore, this investigation underscores the latent promise of the examined extracts as reservoirs of safe and efficacious analgesic and anti-inflammatory agents, thereby meriting further meticulous exploration. Subsequent research endeavours ought to pivot towards elucidating the phytochemical constituents underpinning the observed effects, alongside unravelling their mechanistic underpinnings across a spectrum of animal models and clinical milieus.

Antimicrobial and Antiplasmodial Activities of Endophytic Fungi Associated with Psidium guajava

Infections due to antimicrobial-resistant microorganisms have become widespread in recent years. Thus, searching for novel antimicrobial agents to combat such pathogens has become crucial. The current study aimed to evaluate the antimicrobial, antiplasmodial, and immunomodulatory activities of the extracts of endophytic fungi isolated from Psidium guajava. Isolation, identification, fermentation, and extraction of the secondary metabolites of the fungal endophytes were carried out following standard procedures. The extracts were subjected to High-Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) analysis to detect their bioactive components. The Antimicrobial activity and Minimum Inhibitory Concentration of the fungal extracts were evaluated against pure cultures of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Salmonella typhi, and Klebsiella pneumonia using Agar well diffusion and Agar dilution method respectively. The acute toxicity study (LD50) was carried out using Lorke’s method. The extracts were tested in vivo in mice for antiplasmodial activity against Plasmodium berghei and in vitro against Plasmodium falciparum using Peter and Reyley's curative test method and WHO standardized micro-test system with modification respectively. The immunomodulatory activity of the extracts was evaluated by cyclophosphamide-induced myelosuppression (hematological parameters). Active extracts were further subjected to Delayed-Type Hypersensitivity Response (DTHR) and Haemagglutination Inhibition Assay using Sheep Red Blood Cells as antigens. The result showed Alternaria sp. (PGL1, PGL2, PGL3), from P. guajava. The HPLC-DAD analysis revealed the presence of bioactive compounds previously reported to have antimicrobial, antiplasmodial, and immunomodulatory properties. The fungal extracts exhibited varying degrees of antimicrobial activity. The LD50 of the fungi extracts was>5000 mg/kg in mice. The extracts at 100 and 200 mg/kg body weight in mice showed varying degrees of antiplasmodial activity. Growth of P. berghei was significantly (p<0.001) inhibited, curative effect ranges from 59.09 – 100%. Schizont maturation of P. falciparum isolates was inhibited and the highest level of inhibition was observed at 1 mg/ml (p<0.05). The fungal extracts reversed the effect of cyclophosphamide-induced reduction in total white blood cell counts and % neutrophil. This study showed that the tested plant harbors species of endophytic fungi that contain numerous secondary metabolites. The endophytic fungi showed prophylactic, immunostimulatory, and antiplasmodial activities, which can be exploited to develop antimicrobial, antiplasmodial, and immunomodulatory agents.

Ecotoxicological Assays with the Calanoid Copepod Acartia tonsa: A Comparison between Mediterranean and Baltic Strains

The use of marine invertebrates in ecotoxicology is important for an integrated approach which takes into consideration physiological responses and chemical levels in environmental matrices. Standard protocols have been developed and organisms belonging to different trophic levels are needed as model organisms to evaluate toxicant bioavailability and assess their impact on marine biota. The calanoid copepod Acartia tonsa is commonly used in ecotoxicology due to its widespread distribution and well-studied biology. However, different strains coming from various geographical areas are available, and possible variations in physiological characteristics raise concerns about the comparability of ecotoxicological results. This study compares the life cycle assessment and sensitivity of Adriatic and Baltic strains of A. tonsa exposed to nickel (Ni2+) in standardized acute and semi-chronic tests. Life cycle assessments revealed differences in egg production, egg-hatching success, and naupliar viability between the strains. The acute toxicity test demonstrated the significantly higher sensitivity of Adriatic strain nauplii to Ni2+ compared to the Baltic strain, whereas the semi-chronic test showed no significant difference in sensitivity between the strains. These findings suggest that while strain-specific differences exist in different geographical populations, responses to toxicants are not significantly different. Particularly, the semi-chronic assessments with both A. tonsa strains emphasized the robustness of this species as a model organism in ecotoxicology.