Journal of Toxicology最新文献

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.

This study explores the effects of a low glycemic index starch (HR0) produced through double thermal retrogradation (4°C/18 h-30°C/6 h), on the physiology and behavior of mice. HR0 starch exhibited low in vitro and in vivo glycemic indexes of 37 and 51, respectively. Mice fed a high-fat diet supplemented with 33% HR0 starch showed significant reductions in body weight compared to those on a high-fat diet. HR0 supplementation normalized fasting plasma glucose levels in mice, preventing the development of diabetes, while all other high-fat diet groups developed diabetic symptoms. Blood lipid analysis indicated that HR0 reduced triglycerides, LDL cholesterol, and total cholesterol levels while increasing HDL cholesterol. Histological examinations showed that HR0 improved the health of liver, kidney, and adipose tissues, notably reducing the incidence of fatty liver disease. Behavioral tests demonstrated that HR0 starch enhanced locomotor activity and reduced anxiety levels. These results suggest that HR0 starch can effectively improve metabolic health and may serve as a beneficial dietary supplement for individuals at risk of obesity, diabetes, and cardiovascular diseases.

Fibraurea tinctoria Lour has long been used by the indigenous ethnic groups of Kalimantan in the traditional treatment of malaria, jaundice, and diabetes mellitus. This study aimed to evaluate the drug-likeness and ADMET properties of the active compounds berberine, palmatine, and jatrorrhizine and to assess the acute toxicity of the plant extract using in silico and in vivo approaches. In silico analysis was performed using the pkCSM, ProTox-II, and SwissADME online web servers to predict drug-likeness and ADMET of compounds from Fibraurea tinctoria Lour. The in vivo acute toxicity of the extract was evaluated according to the Organization for Economic Cooperation and Development (OECD) 425 guideline. In silico studies have demonstrated that berberine, palmatine, and jatrorrhizine exhibit favorable drug-likeness and pharmacokinetic properties but indicate potential oral toxicity. In contrast, the in vivo acute toxicity study revealed no toxicity or adverse effects, with an LD₅₀ greater than 5000 mg/kg. These findings indicate that despite the in silico prediction showing the potential toxicity of these three compounds, the extract exhibited relative safety based on in vivo tests and has the potential for further pharmacological development.

Background: Microplastics (MPs) and the endocrine-disrupting chemicals associated with them, including bisphenol A (BPA) and phthalates, have been identified as potential factors contributing to the increasing rates of metabolic syndrome (MetS) and colorectal carcinogenesis. Despite rising concerns in this area, a thorough synthesis of the mechanistic and epidemiological data connecting MPs to these health issues is currently absent. For consistency in this review, early-onset colorectal cancer is defined as colorectal cancer diagnosed before the age of 50 years, in line with recent epidemiological studies. Chronic exposure to MPs is defined as sustained exposure lasting at least 8 weeks in animal models or multiple years in human observational studies. These standardized definitions ensure clarity when comparing outcomes across diverse study designs.

Objective: This systematic review aims to evaluate current human, animal, and in vitro evidence on the dual impact of MP exposure on metabolic dysregulation and pathways involved in colorectal carcinogenesis.

Methods: A systematic search was performed across PubMed, Scopus, Web of Science, and EMBASE in accordance with PRISMA 2020 guidelines. The review incorporated 45 studies: 18 observational studies involving humans, 17 animal studies, and 10 in vitro investigations. The outcomes analyzed included components of MetS, precursors to colonic neoplasia, and relevant biological mechanisms.

Results: Exposure to MPs correlated with an increased risk of insulin resistance, obesity, and dyslipidemia. It also contributed to heightened inflammatory responses, alterations in gut microbiota composition, and dysfunction of the epithelial barrier. Furthermore, chronic exposure led to colonic inflammation and an elevation in tumorigenic markers, such as β-catenin (a key oncogenic protein in the Wnt signaling pathway) and COX-2 (an inflammatory enzyme implicated in tumor progression).

Conclusion: The results indicate a biologically plausible connection between MP exposure and the development of both MetS and colorectal carcinogenesis pathways, rather than a direct clinical association with early-onset colorectal cancer.

Chemical warfare means the use of chemical agents that have direct toxic effects on animals, plants and humans, as weapons. The first documented use of a chemical agent for warfare purposes occurred in ancient times around 10,000 BCE in South Africa when weapons were dipped in chemicals and then used to attack and defend from enemies. However, much of the evidence lacks detail to provide thorough accounts of such events. Nevertheless, we aimed to systematically gather the most comprehensive account of all publicly known incidents involving chemical weapons throughout history. We identified 121 instances of chemical weapon use between 10,000 BCE and October 2023 spanning 49 countries and causing at minimum 2,110,360 injuries and 2,930,769 deaths. Across the 121 incidents, at least 165 chemical agents were used. Of the known chemical agents, the top three were sulphur mustard (n = 16, 12.1%), hydrogen cyanide (n = 12, 7.3%) and chlorine gas (n = 11, 6.7%). Of the known chemical classes, the top three used were vesicants (blistering agents) (n = 31, 18.8%), choking (pulmonary) agents (n = 18, 10.9%) and nerve agents (n = 18, 10.9%). If a chemical agent was not reported, the chemical class was reported as unknown (n = 35, 21.2%). A small number of chemical weapons were used that fell outside of the main categories of agents (n = 20, 12.1%). Chemical weapons remain a serious concern locally and globally, and there are few data on the global epidemiology of such incidents. Prevention, early detection and rapid response are key and can be enabled by global surveillance for chemical incidents.