Journal of Toxicology最新文献

D-Allulose is a rare monosaccharide structurally similar to D-fructose, characterized by low caloric content and relatively high sweetness. This study aimed to conduct a 90-day oral toxicity test to systemically evaluate the potential toxicological effects of D-allulose produced via a novel one-step fermentation process using genetically engineered Escherichia coli AS10 strain, which was genetically modified to express enzymes involved in the biosynthesis of D-allulose from D-glucose. The objectives were to determine its NOAEL, provide scientific evidence for the safety evaluation of this innovative food ingredient, and meet the regulatory requirements for the safety assessment of a novel process-derived food product. A total of 96 SD rats were randomly divided into four groups (24 rats per group, with equal numbers of males and females): a control group (basal feed) and three treatment groups fed with feed containing 2.5%, 5.0%, and 10.0% D-allulose (corresponding to estimated dietary intakes of 2000, 4000, and 8000 mg/kg body weight per day, respectively, based on an assumed daily feed intake of 8% of body weight) for 90 consecutive days. A comprehensive battery of toxicological assessments was performed on each animal, including measurements on body weight, food consumption, feed efficiency ratios, hematological metrics, serum biochemical profiles, organ weights, and histopathological examinations. No treatment-related mortality or overt toxic symptoms were observed in any group during the study period. Statistically significant differences were noted in partial metrics (e.g., body weight, feed consumption, HCT%, PLT, ALP, TC, and absolute/relative weight of kidney) between treatment groups and control group, but these changes were deemed nontoxicologically significant due to consistency with normal physiological variability (within the historical in-house reference ranges) or lack of corresponding pathological lesions. The NOAEL of D-allulose was established at 8000 mg/kg BW/day in rats, confirming its safety for use as a food ingredient.

Background: Today, methadone is widely used to control drug abuse. This has made this synthetic opioid widely available to the public, and its overdose has become one of the most common causes of poisoning. This study aimed to investigate changes in liver enzyme levels in patients who were referred and hospitalized due to acute methadone poisoning.

Methods: This cross-sectional study was conducted from July 2023 to June 2024 on patients hospitalized with acute methadone poisoning in the poisoning department of Imam Reza Hospital in Mashhad. Demographic and clinical information of the patients was recorded at the time of admission. Liver enzyme levels, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), were measured at the time of admission and before discharge. Finally, the data were analyzed using appropriate statistical tests using SPSS software.

Results: A total of 49 patients were studied in this study. The mean age of the patients was 24.65 years, and 34 (69.4%) of them were female. 26% of the patients had increased AST, and 22% had increased ALT. In 80% of cases, the increase in these two enzymes was less than three times the normal limit, and no significant increase was observed. ALP was also increased in 12.2% of the patients. In total, at least one liver enzyme was increased in 38.8% of the patients. No significant correlation was observed between the dose of methadone consumed and the levels of liver enzymes (AST, ALT, and ALP) (p > 0.05). In addition, the increased levels of enzymes returned to normal levels during hospitalization.

Conclusion: Elevated liver enzymes are a common finding in patients with methadone intoxication; however, we were unable to demonstrate a correlation between the dose of methadone consumed and serum levels of liver enzymes.

This narrative review synthesizes peer-reviewed studies retrieved from major scientific databases addressing the environmental and biological applications of graphene-based nanomaterials for cadmium mitigation. Cadmium (Cd) is a nonessential and highly toxic heavy metal with a prolonged biological half-life and extensive environmental persistence, posing substantial risks to the ecosystem and human health. Exposure to cadmium is linked to nephrotoxicity, carcinogenicity, endocrine disruption, and reproductive issues. This review critically evaluates the emerging role of graphene-based nanoparticles, particularly graphene oxide (GO) and its functional derivatives, in reducing Cd bioavailability in soil, wastewater, and along the food chain. GO-based composites can achieve adsorption capacities above approximately 50-500 mg cadmium per gram of material, depending on functionalization and matrix, highlighting their substantial removal potential. Recent evidence demonstrates graphene's dual functionality: as a potent adsorbent for cadmium ions and as an enhancer of biological tolerance to cadmium-induced toxicity in both plants and human cells. To our knowledge, this review is the first to comprehensively integrate cross-disciplinary evidence on (i) the integration of engineered graphene membranes for selective filtration under pressure, (ii) GO-enhanced soil amendments that reduce cadmium uptake, (iii) thiol-functionalized composites for precise metal adsorption, and (iv) magnetic graphene nanoparticles enabling suitable cadmium removal. By integrating cross-disciplinary evidence, we provide a comprehensive roadmap for implementing graphene nanoenabled environmental interventions. Despite promising outcomes, most available evidence is based on laboratory-scale studies, with limited field-scale validation and an incomplete understanding of the long-term environmental fate and ecotoxicity of graphene nanomaterials.

Arsenic trioxide (ATO), utilized in the treatment of acute promyelocytic leukemia (APL), presents significant renal toxicity that restricts its clinical usage. The potential effects of empagliflozin (EMPA) on ATO-induced nephrotoxicity remain unexplored. This study aims to investigate whether EMPA can alleviate ATO-induced nephrotoxicity in both animal and cellular models, as well as to further explore the underlying mechanisms. EMPA can improve renal function in mice and alleviate ATO-induced structural damage to the kidneys. EMPA treatment effectively inhibits ATO-induced oxidative stress and reduces apoptosis. EMPA significantly decreases the production of ROS in cultured HEK293T cells, lowers the apoptotic rate, and safeguards mitochondrial function. EMPA upregulates the SIRT1/Akt/Nrf2 pathway and addresses ATO-induced autophagy dysfunction. These findings suggest that EMPA may ameliorate ATO-induced renal toxicity by activating the SIRT1/Akt/Nrf2 signaling pathway, which is associated with the suppression of oxidative stress, reduction of apoptosis, and protection of mitochondrial functionality.

The anticancer drug pegylated liposomal doxorubicin (PLD) can cause hand-foot syndrome (HFS), a condition that develops in the palms and soles when pressure is frequently applied. Strategies to address HFS are insufficient. Dexrazoxane (DXZ) protects against doxorubicin-induced cardiotoxicity, possibly via reducing topoisomerase (Topo) IIβ levels in myocytes. Previously, we developed a rat model that used three tail-vein doses of PLD to induce HFS-like skin damage. In this study, we generated a simple mouse model of HFS-like skin damage using rubber fastening and PLD treatment to examine potential protective effects from DXZ. Male ddY mice received PLD (16.5 mg/kg) intravenously, with the flank skin compressed by a rubber band for 48 h. DXZ (50 and 250 mg/kg) was administered intraperitoneally twice prior to PLD. Skin tissues were removed on Day 12, fixed, and stained with hematoxylin-eosin to assess epidermal thickening. Western blotting identified the expression of γH2AX (a DNA damage marker) and the doxorubicin targets Topo IIα/β. After Day 8, DXZ (both concentrations) + PLD groups exhibited less skin damage than the PLD group. The PLD group showed greater epidermal layer thickening than both the control and DXZ + PLD groups. γH2AX and Topo IIβ expression increased in the back and flank regions of PLD-treated mice but was suppressed under DXZ + PLD treatment. Although not significant, Topo IIα expression followed an analogous pattern to Topo IIβ expression. In conclusion, we demonstrated that DXZ inhibited PLD-induced skin damage.

Background: The accumulation of unused and expired medications (UEM) in households represents a growing public health and environmental concern, particularly in low-resource settings such as the Democratic Republic of Congo (DRC), where safe disposal infrastructure is limited and regulatory frameworks are weak. In the Boma Health Zone, previous environmental studies have documented pollution of the Kalamu River by solid and liquid waste, including pharmaceuticals, altering its physico-chemical and bacteriological properties. However, no systems for safe medication disposal are available to the public, and empirical data on household UEM disposal practices in the DRC are virtually nonexistent, highlighting the critical need for this research.

Objective: This study assessed the knowledge, attitude, and practice (KAP) regarding UEM disposal among households in the Boma Health Zone, DRC.

Methods: A community-based cross-sectional survey was conducted in April 2024 among 384 households, selected using a four-stage random sampling technique. Data were collected through face-to-face interviews using a structured questionnaire adapted from validated KAP surveys and administered via the Open Data Kit (ODK) app. Reliability was assessed using Cronbach's alpha (α = 0.78). Descriptive statistics and cross-tabulations were performed using STATA version 14. Missing data were checked at entry via built-in ODK validations, and incomplete questionnaires were excluded from analysis.

Results: More than half of households (53.4%, n = 205) stored UEM, primarily due to symptom resolution (70.6%, n = 271). Awareness of safe disposal was poor: only 12.8% (n = 49) had received prior information, and 94.0% (n = 361) were unaware of take-back systems. Overall, 72.9% (n = 276) had low awareness scores. Attitudes were more favorable, with 53.4% (n = 205) displaying a positive attitude and a majority (53.5%, n = 207) supporting mandatory take-back programs. However, unsafe practices dominated: the most common methods for disposing of expired medications were burning (41.7%, n = 160) and disposal in household waste (32.8%, n = 126). Only 4.4% (n = 17) returned expired medicines to a pharmacy, resulting in 98.7% (n = 379) being classified as having poor disposal practices.

Conclusion: Critical gaps in awareness and practice regarding UEM disposal persist in Boma, despite a willingness to engage in safer practices. Urgent, multilevel interventions are needed, including community awareness campaigns, the establishment of accessible take-back programs, and the development of a national pharmaceutical waste management policy.

[This corrects the article DOI: 10.1155/2023/7398724.].

Objective: To evaluate the acute toxicity of essential oils with repellent potential, diethyltoluamide (DEET), and cypermethrin on Porcellio laevis.

Methods: Randomized preclinical trial with a factorial and controlled arrangement on three essential oils (Eucalyptus globulus, Mentha piperita, and Cymbopogon citratus) at 0.1%, 1%, and 10%, respectively, DEET at 10% and cypermethrin at 0.1%. Each experimental group consisted of 10 specimens, 2-3-mm-long, of P. laevis. Toxicity was measured by specimen mortality at 3, 24, and 48 h postexposure. Nonparametric inferential statistics were used to compare mortality between the groups. The InfoStat/E software, Version 2020, was used for analysis.

Results: Essential oils at concentrations of 0.1% and 1% showed similar toxicity to each other (mortality of 10%-20%) but significantly lower compared to cypermethrin and DEET (mortality of 100%). However, essential oils at 10% reached median mortality rates above 70%. Likewise, similar effects were observed at concentrations of 0.1% and 1.0% and at 24 and 48 h. The LC 50 at 24 h was 7.8% (CI 95%: 5.2-9.8), 6.1% (CI 95%: 4.9-7.4), and 9.8% (CI 95%: 8.9-10.6) for E. globulus, M. piperita, and C. citratus, respectively.

Conclusions: The evaluated essential oils showed lower acute toxicity compared to DEET and cypermethrin, depending on concentration and time.

Background: Fine particulate matter (PM2.5) has been significantly linked to the progression of various neurological and neurodegenerative diseases.

Objective: This review aims to elucidate the molecular and pathophysiological effects induced by chronic exposure to PM2.5 in neurological and neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, multiple sclerosis, and epilepsy.

Introduction: PM2.5 penetrates the central nervous system (CNS) via the olfactory nerve or by disrupting the blood-brain barrier (BBB), triggering oxidative stress, neuroinflammation, mitochondrial dysfunction, and epigenetic alterations.

Discussion: In Alzheimer's and Parkinson's diseases, PM2.5 exacerbates the accumulation of β-amyloid, hyperphosphorylated tau, and α-synuclein, while in Huntington's disease, it worsens toxicity mediated by mutant huntingtin. In multiple sclerosis, these particles intensify neuroinflammation and axonal damage, whereas in epilepsy, they promote neuronal hyperexcitability and recurrent seizures. These mechanisms contribute to neuronal damage, symptom progression, and functional decline.

Conclusion: This evidence highlights the urgent need for strict environmental policies to reduce PM2.5 exposure and further research to develop therapeutic strategies that mitigate its effects on neurological diseases, thereby improving the health of vulnerable populations.

Background: Astragalus membranaceus has a long-standing history of use in traditional Chinese medicine (TCM). Despite its extensive historical application and the emerging scientific evidence supporting its medicinal value, the safety of its extracts, particularly concerning subchronic toxicity, remains inadequately characterized.

Aim: This study conducted a subchronic toxicity assessment of Astragalus root water extract (AWE) in Sprague-Dawley rats to evaluate its safety profile.

Methodology: The safety of AWE was evaluated through a 90-day repeated-dose toxicity study, administering a constant daily dose of 47 g of crude drug per kilogram of body weight. The animals were assessed for body weight, food consumption, rectal temperature, and rotarod performance, alongside hematological and biochemical parameters, bone marrow and immune parameters, and underwent gross necropsy and histopathological examination.

Results: No treatment-related mortality, clinical abnormalities, or gross/histopathological changes were observed. Hematological evaluations, clinical biochemical analyses, bone marrow cytology assessments, and spleen immune typing did not reveal any adverse changes. Compared to the control group, rats treated with AWE exhibited a transient decrease in food intake across five different 24-h intervals, as well as a significant reduction in rectal temperature on Day 90. On the 90th day, the latency period on the rotating rod decreased significantly; however, during the subsequent 30-day recovery phase, all parameters returned to baseline levels. Additionally, absolute and relative organ weights, weight gain, and fat mass remained unaffected.

Conclusion: The high-dose administration of AWE did not exhibit significant toxic effects in Sprague-Dawley rats, thereby supporting its safety within a certain dose range.