Toxicology Reports最新文献

Vitamin D (Vit D) has gained significant attention in health research recently as a result of its potential protective effects against various cellular damages. This study aimed to investigate the ability of vitamin D to mitigate deoxyribonucleic acid (DNA) fragmentation in liver cells and bone marrow cytotoxicity induced by chloramphenicol (CAP). Sixty male albino mice were divided into six groups: control, chloramphenicol-treated (250 and 500 mg/kg body weight, 5 days per week for 4 weeks), vitamin D-treated (800 IU/kg body weight, 5 days per week for 4 weeks) and vitamin D plus chloramphenicol-treated groups. Results of DNA fragmentation test revealed that oral treatment with low and high doses of CAP significantly increased the frequency of DNA fragmentation in liver cells in comparison with the control, whereas oral treatment with vitamin D alone or plus low and high doses of chloramphenicol significantly reduced the genotoxicity in liver cells in comparison with the control group. Micronucleus analysis showed that CAP treatment at low and high doses significantly increased micronuclei formation and cytotoxicity in bone marrow cells. However, vitamin D significantly reduced the micronuclei formation in bone marrow cells of mice treated with chloramphenicol. Vitamin D alone showed no significant difference in the frequency of micronuclei and bone marrow cytotoxicity compared to the control group. Accordingly, further research exploring the mechanisms underlying the protective effects of vitamin D and investigating optimal dosing regimens is warranted. Also, clinical studies evaluating the efficacy of vitamin D supplementation to mitigate the adverse effects of chloramphenicol in human patients are recommended.

In this study, green fluorescent carbon quantum dots (CQDs) with remarkable stability, water solubility, and biocompatibility were synthesized from hazelnut husk (HH) waste material using a novel approach by the pyrolysis method. The optical properties of the synthesized HH-CQDs were characterized by UV-Vis and fluorescence spectroscopy (PL), while their structural properties were characterized using various techniques, including transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). TEM images revealed that HH-CQDs had a spherical shape with diameters ranging from 2 to 10 nm. The fluorescence quantum yield of these CQDs was measured as 0.04. Furthermore, CQDs were very effective at finding aflatoxin B1 (AFB1) using a fluorescence resonance energy transfer (FRET) mechanism, with a clear fluorescence emission peak seen at 451 nm. The photoluminescent properties of CQDs were evaluated under various pH conditions, showing a blue shift and increased fluorescence intensity at pH 9-10, suggesting their potential use in pH-sensitive sensor applications. This study demonstrates the selective and sensitive detection of AFB1 using HH-CQDs, with a strong linear relationship (R² = 0.9936) between fluorescence intensity and AFB1 concentration in the range of 25-250 ppm, and high accuracy in real food samples, including 81.56 % in corn, 98.64 % in milk, and 95.73 % in peanuts. This eco-friendly and cost-effective synthesis method offers a promising alternative for AFB1 detection in food samples by utilizing waste material to create valuable analytical tools.

The multiple mutation of the spike (S) protein of the Omicron SARS-CoV-2 variant is a major concern, as it has been implicated in the severity of COVID-19 and its complications. These mutations have been attributed to COVID-19-infected immune-compromised individuals, with HIV patients being suspected to top the list. The present study investigated the mutation of the S protein of the omicron variant in comparison to the Delta and Wuhan variants. It also investigated the molecular interactions of antiretroviral drugs (ARVd) vis-à-vis dolutegravir, lamivudine, tenofovir-disoproxilfumarate and lenacapavir with the initiation and termination codons of the mRNAs of the mutated proteins of the omicron variant using computational tools. The complete genome sequences of the respective S proteins for omicron (OM066778.1), Delta (OK091006.1) and Wuhan (NC 045512.2) SARS-CoV-2 variants were retrieved from the National Center for Biotechnology Information (NCBI) database. Evolutionary analysis revealed high trends of mutations in the S protein of the omicron SARS-CoV-2 variant compared to the delta and Wuhan variants coupled with 68 % homology. The sequences of the translation initiation sites (TISs), translation termination sites (TTSs), high mutation region-1 (HMR1) and high region mutation-2 (HMR2) mRNAs were retrieved from the full genome of the omicron variant S protein. Molecular docking analysis revealed strong molecular interactions of ARVd with TISs, TTSs, HMR1 and HMR2 of the S protein mRNA. These results indicate mutations in the S protein of the Omicron SARS-CoV-2 variant compared to the Delta and Wuhan variants. These mutation points may present new therapeutic targets for COVID-19.

Doxorubicin, as an antibiotic causes toxicity in human tissues through the generation of oxidant species; however, Solanum anomalum (Solanaceae) is ethnopharmacologically and scientifically reported to possess antidotal activities. This study was designed to validate the antidotal potency of the plant's bioactive compounds on rats' testes following induction with doxorubicin through the evaluation of oxidative stress markers, lipid peroxidation indices, testes' histological sections, and in silico profiling of the plant's bioactive compounds against some proteins. The collection and preparation of the plant extract, testicular toxicity induction, seminal analysis, assay of testosterone and oxidative stress markers, lipid peroxidation profiling, histomorphological studies, retrieval of catalase, superoxide dismutase, and glutathione peroxidase from PDB, GC-MS, ADME, and docking analyses followed standard protocols. In addition, Swiss-ADME and Auto Dock Vina 4.2 tool enabled drug-likeness, pharmacokinetic properties, and molecular docking analyses. The administration of differential dosages (70-210 mg/kg) of the extract to male rats induced with doxorubicin revealed that the serum levels of malondialdehyde (MDA), total cholesterol (TC), triglycerides (TG), LDL-C, and VLDL-C were significantly decreased, whereas significant increases were observed in the levels of HDL-C, testosterone, GSH, SOD, GPx, and CAT when compared to negative control animals. The histological findings suggested strong testicular protective potential that corroborated the chemical pathological alterations. Therefore, the compounds (squalene, β-sitosterol, cis-pinane, 1,4-Eicosadiene, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, heptacosane, and bicyclo-heptanes-2,5,6-trimethylsilyl) characterized from S. anomalum leaf that revealed remarkable binding energies, pharmacokinetics, physicochemical, and drug-likeness properties contributed to the attenuation of the doxorubicin-induced testicular toxicity; hence, they possess antidotal activities.

Adverse cardiovascular events (ACVE) are serious sequelae of acute poisoning with cardiotoxic agents. They include shock, acute myocardial injury, ventricular dysrhythmias, and cardiac arrest. Early identification of high-risk patients could improve their prognosis. Therefore, this study developed a risk-prediction nomogram to assess the risk of ACVE in patients with acute cardiotoxicities. This prospective cohort study was conducted at Tanta University Poison Control Center, Tanta, Egypt, from April 2023 to March 2024. It included 186 patients with acute cardiotoxic agent poisoning. ACVE occurred in 36 % of patients and were significantly associated with ICU admission and mortality (P<0.001). A multivariable logistic regression model was generated that included six significant predictors; modified shock index (AOR of 6.431, 95 % CI: 1.361-30.398, P = 0.02), serum bicarbonate level (AOR of 0.747, 95 % CI: 0.661-0.843, P = 0.001), oxygen saturation (AOR of 0.867, 95 % CI: 0.810-0.929, P = 0.001), ST segment changes (AOR of 9.196, 95 % CI: 1.989-42.508, P = 0.011), prolonged QTc (AOR of 3.015, 95 % CI: 0.975-9.325, P = 0.044), and QRS width (AOR of 1.032, 95 % CI: 1.001-1.064, P = 0.009). The nomogram was statistically significant (P <0.001) and could predict ACVE with 89.2 % accuracy. A Receiver Operating Characteristics analysis was conducted to ensure the nomogram's discrimination ability (Area under the curve =0.956). Also, the calibration curve was drawn using the bootstrapping method to ensure the nomogram's internal validity. The current study provided an easily applicable nomogram that could accurately predict ACVE following acute cardiotoxicities, regardless of the causative agent.

[This corrects the article DOI: 10.1016/j.toxrep.2020.10.007.].

Nanoparticles are attracting attention for their potential therapeutic applications, particularly in cancer therapy, underscoring their importance in medicine. Cadmium sulfide nanoparticles, known for their robust catalytic and optical properties, are classified as chalcogenides and show promise for cancer diagnosis and treatment. Neuroblastoma, a common solid tumor in childhood, poses a significant health threat with different outcomes depending on its biological subtype. This study evaluated the antiproliferative effects of cadmium sulfide nanoparticles on the SY-SH5Y cell line. Walnut shell extract and Na₂S were used to facilitate the synthesis of cadmium sulfide nanoparticles by green synthesis. Characterization of the synthesized cadmium sulfide nanoparticles was performed by Fourier transform infrared spectroscopy, scanning electron microscopy, and x-ray diffraction analyses. The SH-SY5Y cell line was cultured in a standard cell culture medium and then exposed to different cadmium sulfide nanoparticles (10-25-50-75-100 µg/mL) for 24 hours. Cell viability, oxidant, and antioxidant levels were then assessed using a 3-(4,5-dimetiltiyazol-2-il)-2,5-difeniltetrazolyum bromür, total antioxidant, and total oxidant assays. The data showed that applying 100 μg/mL cadmium sulfide nanoparticles resulted in a significant decrease in cancer cell viability of up to 40.96 % (p<0.05). The cadmium sulfide nanoparticles had a dose-dependent effect on the SH-SY5Y cell line. Furthermore, cadmium sulfide nanoparticles increased oxidative activity in neuroblastoma cells, which was consistent with the results of the 3-(4,5-dimetiltiyazol-2-il)-2,5-difeniltetrazolyum bromür assay. In conclusion, cadmium sulfide nanoparticles exhibited potent activity against the neuroblastoma cell. This study highlights the antiproliferative efficacy of green-synthesized cadmium sulfide nanoparticles with walnut shell extract on relevant cancer cell lines.

Background: Methotrexate (MTX) is an extensively used chemotherapeutic agent with well-characterized toxicity profiles. This case report describes the clinical presentation, management, and outcome of a patient presenting with severe MTX toxicity.

Case presentation: A 35-year-old Bangladeshi female was admitted on March 9, 2024, with severe mucosal ulcerations, painful skin lesions, and gastrointestinal bleeding after ingesting Methotrexate daily for 12 days by mistake instead of the medication prescribed to her. On physical examination, there was severe injury involving skin and mucosa. The laboratory results showed severe pancytopenia and liver and kidney function in derangement. There was gradual improvement with the prompt withdrawal of Methotrexate, Folinic Acid therapy, and supportive therapies; most of the laboratory values returned to normal by day 14.

Conclusion: This case was one of severe Methotrexate poisoning, leading to profound systemic toxicity. Thus, timely recognition, immediate drug withdrawal, and aggressive supportive care comprising Folinic Acid therapy and hydration played a major role in this patient's management.

The present study was undertaken to investigate the effect of Achras sapota (A. sapota) fruits in scopolamine induced amnesia & cognitive impairment in mice. A. sapota commonly known as Chiku belong to Sapotaceae family. Memory impairment was induced in Swiss albino mice by a single injection of scopolamine (1 mg/kg, i.p). Animals (Swiss albino mice) were divided into five separate groups of six animals each. Positive control group received CMC (carboxy methyl cellulose) as vehicle, negative control group received scopolamine along with vehicle, standard group received Donepezil (5 mg/kg, p.o) with scopolamine. Ethanolic extract of A. sapota (EEAS, 200 mg & 400 mg/kg, p.o) was administered to group Test 1 and Test 2 respectively along with scopolamine. Elevated plus maze (EPM), modified passive avoidance test, Morris water maze (MWM) models and locomotor activity were employed as exteroceptive behaviour models to assess learning and memory activity. Thereafter lipid peroxidation, reduced glutathione and catalase level were estimated in homogenized brain of mice. The extract showed the presence of different chemical constituents like flavonoids, tannins, glycosides and alkaloids. The pre-treatment of mice with EEAS (200 mg/kg & 400 mg/kg) significantly reduced the scopolamine induced increase in EL time in MWM, whereas in EPM administration of extract produces significant decrease in TL. In Modified passive avoidance test significant increase in SDL, was shown by the animals. In locomotor activity, treatment of EEAS did not alter normal locomotor activity whereas lipid peroxidation was significantly decreased, catalase & reduced glutathione levels were significantly increased in animals of test 1 & test 2 when compared to negative control group. Hence it would be worthwhile to explore the potential of this plant in management of cognitive impairment and other memory disorders.

(S)-Equol is a chemically synthesized nutraceutical compound and its consumption provides several health benefits for humans. The new nutraceutical, enantiopure (S)-Equol was studied for acute and sub-chronic toxicity in Sprague Dawley Rats. The oral acute toxicity study showed that (S)-Equol is safe > 2000-5000 mg/kg body weight and it classified into GHS category 5/Unclassified. The repeated dose administration of (S)-Equol at dose levels of 20, 60, and 160 mg/kg body weight for 14 days and 250, 500, and 1000 mg/kg body weight for 90-consecitve days. The 14 days repeated-dose toxicity study showed no adverse effects in Sprague Dawley rats. The 90-day repeated dose toxicity study showed a reduction in body weight gain than that of control group. No treatment-related contrary effects were perceived on haematology, clinical chemistry, coagulation, urine parameters analysed, organ weights (absolute and relative), neurological and ophthalmological examination. No treatment-related abnormal gross pathological findings were obtained from gross necropsy. However, as a treatment-related effect, a significant decrease in cholesterol levels for 14 and 90 days of repeated dose administration was observed, which is considered as a pharmacological class effect of the (S)-Equol. In comparison to the corresponding vehicle control group, the high dose treatment group for both sexes showed no treatment-related histopathological abnormalities. For female rats, the no-observed-adverse-effect-level (NOAEL) was 250 mg/kg/day and for male rats, the lowest-observed-adverse-effect level (LOAEL) was 250 mg/kg/day.