Journal of Applied Toxicology最新文献

Foeniculum vulgare, commonly known as fennel, has a long history of use in traditional medicine, particularly for treating problems related to the digestive, endocrine, reproductive, and respiratory systems. The major constituents found in fennel seed extracts are trans-anethole (68.6%-75.0%), fenchone (8.40%-14.7%), and methyl chavicol (5.09%-9.10%). However, before introducing this plant into the human environment, it is essential to understand its toxicological properties. In this study, we investigated the acute and sub-acute toxicity of methanolic extracts of F. vulgare. A phytochemical screening was performed to identify the major chemical constituents of the plant. For the acute toxicity study, female Wistar rats received a single dose of the methanolic extract of F. vulgare at doses of 1000, 2000, 3000, and 5000 mg/kg for 14 days. In the sub-acute toxicity study, the methanolic extract of F. vulgare was administered orally daily at doses of 125, 250, and 500 mg/kg for 28 days. Hematological, biochemical, and histological changes were evaluated. Phytochemical tests were also performed. The phytochemical analysis showed that the methanolic extract of F. vulgare is rich in flavonoids, catechic, gallic tannins, and total polyphenols. Toxicological tests showed no animal deaths, suggesting that the LD₅₀ was greater than 5000 mg/kg. In the sub-acute oral toxicity study, no significant differences were observed in body weight, food consumption, or water intake. Additionally, there were no significant changes in hematological and biochemical parameters or differences in the macroscopic and microscopic examination of organs. Therefore, this study concludes that the methanolic extract of F. vulgare, at the doses tested, is considered non-toxic under the conditions evaluated.

The high global prevalence of depression and its growing impact highlight an urgent need for better models and antidepressant treatments. Hence, in the present research, the effects of the anxiolytic drug diazepam and the antidepressant sertraline on behavioral, biochemical, and molecular parameters in zebrafish (Danio rerio) were investigated using the Unpredictable Chronic Stress (UCS) protocol. The Novel Tank Test (NTT) was used to evaluate the behavioral changes, while biochemical analysis was performed by cortisol measurement. Molecular analysis of proinflammatory (TNF-α, IL-6) and anti-inflammatory (IL-10) cytokine gene expression was also performed using RT-PCR. The acquired data were analyzed using two-way ANOVA in SPSS software. It was found that the UCS protocol induced significant behavioral and neuroendocrine alterations. Treatment with diazepam, sertraline, and their combination led to significant improvements in behavioral outcomes, as indicated by increased time spent and number of entries in the top zone of the tank. Additionally, these treatments reduced the expression of inflammatory cytokine genes (TNF-α, IL-6), such that sertraline showed a significant reduction in cortisol levels (from 1.01 ± 0.07 ng/g to 0.15 ± 0.04 ng/g). These findings reinforce the utility of the zebrafish model for elucidating stress-induced pathophysiology and validate the UCS protocol as a robust method for assessing potential treatments of psychiatric therapeutics.

Dehydroacetic acid (DA) and benzoic acid (BA) are used as preservative agents in cosmetics in Korea at maximum concentrations of 0.6% and 0.5%, respectively. Prior to conducting the percutaneous absorption study, analytical methods were developed and validated for the quantification of DA and BA in various matrices including swab (SW), stratum corneum (SC), full-thickness skin (dermis + epidermis, SK), and receptor fluid (RF). These methods demonstrated excellent linearity (r² = 0.9992-0.9998 for DA, 0.9996-0.9999 for BA), high accuracy (91.53%-111.70% and 96.04%-101.47%), and acceptable precision (1.90%-10.16% and 1.30%-5.48%), in accordance with regulatory validation guidelines. Percutaneous absorption was evaluated using a Franz diffusion cell system with dermatomed dorsal minipig skin. Lotion formulations containing DA (0.12%, 0.24%, and 0.6%) and BA (0.1%, 0.2%, and 0.5%) were topically applied at 10 mg/cm². After 24 h of exposure, concentrations of each compound in the matrices were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total percutaneous absorption rates of DA were 104.13% ± 5.86%, 91.42% ± 4.05%, and 101.18% ± 7.82% for the 0.12%, 0.24%, and 0.6% formulations, respectively. For BA, the corresponding absorption rates were 65.85% ± 5.80%, 51.54% ± 8.97%, and 79.10% ± 5.65%. This indicates that DA and BA were mostly absorbed through the skin within the permitted concentration limits, suggesting that consideration of skin absorption rate is important when evaluating the safety of preservative exposure through the skin.

Parabens (PBs) are compounds widely used as preservatives in personal care products, food, and pharmaceuticals. Methylparaben (MePB) is the most used by different industries due to its chemical properties and low cost. The high daily human exposure to these compounds has raised concerns about their potential effects on health, particularly on reproductive health. Therefore, the aim of this study was to evaluate the effect of the in vitro exposure of porcine oocytes to concentrations of 0, 500, 750, and 1000 μM MePB on the viability of cumulus cells (CCs) and oocytes; oocyte apoptosis and necrosis; DNA integrity of CCs; chromatin integrity of oocytes; maturation, fertilization, and embryo development competence; and embryo viability after in vitro production. The results showed that the viability of oocytes decreased significantly at 1000 μM concentration of MePB, and the viability of CCs decreased at the 750 μM concentration. MePB did not induce apoptosis or necrosis in oocytes. DNA damage in CCs increased at all concentrations tested, from 500 to 1000 μM, and chromatin damage in oocytes was observed at 1000 μM. In vitro oocyte maturation and embryo development rates decreased starting at 750 μM, and total embryo cleavage and viability decreased at 1000 μM. Reduced morulae and blastocyst formation were also observed. These findings suggest that MePB damages both CCs and oocytes, impairing their developmental competence and reducing the production of viable embryos. These findings contribute to understanding the potential effects of MePB on reproductive health and its possible link with fertility problems.

Nanomedicine combines nanotechnology with healthcare, offering transformative possibilities in drug delivery and targeted therapies. The unique properties of nanomaterials-such as their high surface area owing to their microscopic size-make them especially valuable in treating various diseases. Nanogels-polymeric nanomaterials which are designed to be modular-can be enabled to carry both water-soluble and fat-soluble drugs. They enable controlled drug release, protect against metabolic degradation and ensure targeted delivery to cancer cells, thereby reducing undesired drug interaction and systemic toxicity. Elastin, known for its biocompatibility and natural degradability, could play a transformative role in the biomedical landscape. Its mechanical properties can be tailored to improve drug delivery systems with enhanced loading capacities with stimuli responsive release. Enzalutamide (EZA), a drug used in prostate cancer treatment, functions by blocking androgen receptor signalling, thereby inhibiting cancer progression. Yet, resistance to castration treatment triumphs over EZA. Hence constructing a carrier that can enhance EZA's availability within the tumour environment was hypothesized by using elastin protein. The elastin nanogel (ENG) was characterized to understand physical properties such as size, drug encapsulation and rate of drug release. Furthering the need to assess safety of ENG along with its drug encapsulated counterpart. Zebrafish (Danio rerio)-a model organism in biomedical research due to its genetic similarities to humans-was utilized. Translucency of embryos makes it ideal for studying developmental morphology. Its high sensitivity to dissolved substances makes it a valuable model for toxicological studies, environmental monitoring, and drug discovery. This study evaluates the acute toxicity of EZA-loaded ENG at various concentrations (2.5, 5, 7.5 and 10 μg/mL). Toxicological endpoints including viability, mortality, hatching rate, heart rate and morphological abnormalities were assessed at multiple developmental stages (0-96 hpf). At 96 hpf, pooled embryo samples from each group underwent total RNA extraction, cDNA synthesis and quantitative real time PCR targeting seven developmental genes (Hoxa3a, mef2ca, Nkx2.5, pax6a and Runx2a) related to organogenesis, notochord, cardiac, skeletal and spinal cord development, normalized to GAPDH expression. The EZA + ENG group demonstrated reduced toxicity relative to free-form EZA across both phenotypic and molecular parameters, suggesting improved biocompatibility and potential for safer drug delivery. These findings support the utility of elastin-based nano carriers in mitigating the developmental toxicity of antiandrogenic therapies.

Microplastics (MPs), diameter < 5 mm, are becoming a major environmental health concern issue but there is still less information available about the exposure and toxicity of MPs on mammal health. In the current study, we assessed the effects of MPs, Polyvinyl chloride (PVC), and Polystyrene (PS) toxicity on body weight, blood glucose, different blood parameters, and oxidative stress of Wistar albino rats. SEM analysis was performed for the characterization of PVC and PS MPs. In in vivo analysis, the rats were divided into five groups and four groups; Groups 2 to 5 were exposed to PVC and PS at different doses (300 and 1000 mg/kg), and Group 1 was used as a control group. After 8 weeks of exposure, the change in body weight and blood parameters was determined, which showed a significant alteration in the animals' bodies. The addition of polyvinyl chloride and polystyrene to the rats showed a significant decline in body weight (PVC 0.0021: PS 0.0055) and an increase in blood glucose (PVC 0.0006; PS 0.0009). The harmful effect was also analyzed on internal organs which depicted the increase in total cholesterol (PVC 0.0006; PS 0.0009), triglyceride (PVC 0.0001; PS 0.0026), low-density lipoprotein (PVC 0.0226; PS 0.0051), alanine transaminase (PVC; PS < 0.0001), albumin (PVC 0.0037; PS 0.0001), creatinine (PVC; PS < 0.0001), uric acid (PVC 0.0009; PS 0.0014), superoxide dismutase (PVC 0.0025; PS 0.0017), malonaldehyde (PVC; PS < 0.0001) whereas decrease in high density lipoprotein (PVC 0.0255; PS 0.0057), alkaline phosphatase (PVC; PS < 0.0001) and catalase (PVC 0.0095; PS 0.030). Also, the histopathological analysis of the renal and hepatic tissue showed the toxicological effect of PVC and PS. The outcomes of the current work depicted that the MPs, PVC, and PS have toxic effects on animals and humans.

Chlorfenapyr (CFP) is an insecticide known to induce hepatotoxicity through oxidative stress, inflammation, and mitochondrial dysfunction. Resveratrol (RES) exhibits antioxidant and anti-inflammatory properties, and its delivery via chitosan nanoparticles (RES-CNPs) may enhance its protective effects. This study aimed to investigate the hepatoprotective potential of RES and RES-CNPs against CFP-induced liver damage in Wistar rats. Sixty male Wistar rats were randomly divided into six groups (n = 10): control, RES, RES-CNPs, CFP, CFP + RES, and CFP + RES-CNPs. Treatments were administered orally for 30 days. Liver function, lipid profile, oxidative stress markers, antioxidant defense system, energy metabolism, mitochondrial function, inflammatory gene expression, histopathology, and ultrastructure were evaluated exposure significantly decreased total protein, albumin, antioxidant levels (GSH, CAT, SOD, GPX), ATP, and PDH activity, while increasing liver enzymes (AST, ALT, ALP), lipid peroxidation (MDA, PCO), mitochondrial dysfunction, inflammatory gene expression (NF-κB, TNF-α, IL-6), CRP, and total leukocyte count (p < 0.05). Co-administration of RES-CNPs significantly restored these biochemical, molecular, and histological parameters, showing superior efficacy to crude RES in most endpoints and achieving values close to the negative control for several markers (p > 0.05). Histopathological and ultrastructural analyses confirmed CFP-induced hepatocyte degeneration and necrosis, which were ameliorated by RES-CNPs, with near-normal liver architecture and cellular integrity. RES-CNPs effectively mitigate CFP-induced hepatotoxicity by restoring liver function, enhancing antioxidant defenses, preserving mitochondrial function, and suppressing inflammation. RES-CNPs demonstrated superior hepatoprotective effects compared to crude RES, highlighting their potential as a therapeutic strategy against xenobiotic-induced liver injury.

The transport of pharmaceutical compounds into aquatic ecosystems poses a significant environmental threat, particularly due to the presence of drugs that cannot be completely removed during wastewater treatment processes. Diclofenac (DCF), one of the most widely used nonsteroidal anti-inflammatory drugs worldwide, is among the pharmaceuticals frequently detected in aquatic environments due to its high consumption levels and persistence in the environment. It is known that this compound causes neurotoxicity, behavioral disorders, and physiological stress responses in aquatic organisms even at low concentrations. This study aimed to determine the effects of diclofenac exposure on oxidative stress, circadian rhythm, and behavioral parameters in zebrafish larvae. For this purpose, zebrafish embryos and early-stage larvae were exposed to DCF at concentrations of 0.5, 2.5, and 12.5 μg/L for 120 h. Subsequently, to investigate the effect of DCF on oxidative stress, SOD, CAT, GPX, and AChE enzyme activities and gene expression levels were analyzed. To examine its effects on behavior and circadian rhythm, thigmotaxis and locomotor activity analyses were performed. Additionally, to determine the molecular-level effects of behavioral changes, the expression levels of the bdnf, 5ht4, crhr, bmal1, per, and gnat2 genes were analyzed. Overall, our findings indicate that DCF affects behavioral activity, neurotransmitter metabolism, oxidative stress response, circadian rhythm, and retina-related molecular regulators in zebrafish larvae in a multilevel manner. These results highlight the potential risks of pharmaceutical contaminants on neurodevelopmental processes in aquatic ecosystems and demonstrate that even environmental doses can produce complex responses in biological systems.

Poisoning in children is a significant public health concern globally. It represents an important cause of morbidity and mortality in children and adolescents. This study was designed to document types of ingested poisons, the presentation, and outcomes of childhood poisoning at two tertiary hospitals in Harare, Zimbabwe. A hospital-based descriptive cross-sectional study was conducted from March 2019 to June 2020. Data on socio-demographic status, types of poison, clinical assessment, and outcome were collected through an interviewer-administered questionnaire and patients' records. A total of 177 children were admitted with poisoning during the study period, of whom 59.3% were male. The majority (75.1%) were below 6 years of age. Pesticide poisoning was the most common exposure (31.1%). Most of the poisoning cases were accidental (84.7%) and oral ingestion was the primary route (97.7%). According to the poison severity score (PSS), 63.2% of cases were minor and 3.4% were severe. Gastrointestinal symptoms were the most frequent presentation. Two children (1.1%) were admitted into the ICU, 170 (96%) fully recovered, 2 (1.1%) were discharged with sequalae, and 3 (1.7%) died. The three children who died had taken pesticides: one unknown pesticide, aluminum phosphide, and organophosphate (diazinon), and the case fatality rate for the study was 1.7%. Acute poisoning is a significant preventable cause of morbidity in children. Pesticides were the most common cause of poisoning and mortality. The majority of the poisoning was unintentional and occurred mostly in male children below 6 years of age.