Toxicology Research最新文献

The Maxing Kugan Decoction (MKD) is a traditional Chinese medicine prescription specifically designed for respiratory infectious diseases in the northwest region, particularly targeting influenza during the winter and spring seasons. While its clinical efficacy has been established, there is a significant gap in its toxicological safety. This study aims to evaluate the subacute oral toxicity of MKD in rats, focusing on its effects on food consumption, weight, vital signs, haematological parameters, and organ histology. To determine subacute oral toxicity, MKD was administered by gavage at 12.6, 25.2, or 50.4 g/kg/day to male and female rats for 90 days. Meanwhile, the general behavior, body weight, food intake, urine routine parameters, blood biochemical, hematological parameters, coagulation parameters, organ coefficients and organ histopathology were recorded and analyzed. The results showed that experimental rats were healthy and displayed no evidence of toxicity. Furthermore, no mortality or abnormalities in general conditions, including diet and weight, were noted. While the levels of a few indicators changed during administration, their levels remained within the normal range and were not correlated with dose or gender. Overall, no toxicological significance was recorded. Meanwhile, histopathological analysis did not identify abnormal pathological changes in tissue structure and cell morphology across organs, and no significant delayed toxic reactions were detected during the remission period. Overall, our results indicated that oral administration of 50.4 g/kg (60 times the clinical dose in humans) of MKD for three months is safe for SD rats and is not associated with toxic side effects.

One environmental contaminant that affects several tissues and organs, including the testis, is cadmium (Cd). Persea americana is a distinctive fruit with remarkable nutritional and technological qualities in addition to possible health benefits. This study aimed to assess the ameliorative impact of the avocado pulp extract on the testicular toxicity induced by Cd in male rats. In this study, 40 adults' male Wistar albino rats were utilized. Forty rats were randomly divided into four groups: the control group, the avocado extract (AvE)-supplemented group (125 mg/kg, daily), the Cd-treated group (5 mg/kg, daily), and the Cd-treated group that was supplemented with AvE. Cd showed marked testicular oxidative stress, inflammation, testicular injury, and apoptosis. Also, Cd-exposure adversely affected the tissue biosynthesis of male sex hormones and sperm parameters. The treatment of Cd-exposed rats with AvE revealed a pronounced return to normalcy of the oxidative stress markers, as evidenced by a remarkable decrease in the testicular MDA and an improvement of SOD, CAT, and GSH activities. Additionally, AvE had considerably improved the levels of male sexual hormones and the sperm parameters (count, motility, and viability) that were disrupted by cadmium. Likewise, AvE amended the testicular inflammation and histopatholgical features induced by Cd as indicated by decreased levels of NF-κB and IL-1β, as well as by inhibiting COX-2 expression. Further ameliorative effect of AvE was evidenced by attenuation of testicular apoptosis through lowering of Bax expression and Bcl-2 overexpression. P. americana pulp extract has a potential ameliorative role against cadmium-induced oxidative stress, inflammation, and apoptosis in the testicular tissues.

Toluene, a widely used industrial solvent, and environmental noise, a pervasive physical stressor, are both recognized for their harmful effects on health. This study examined the individual and combined effects of toluene and noise exposure on oxidative stress, renal function, pro-inflammatory response, and kidney histopathology. Twenty-four adult male Wistar rats were randomly divided into four groups: control (C), noise exposure (N; 85 dB SPL white noise, 8-16 kHz), toluene exposure (T; 300 ppm), and combined Noise + Toluene exposure (NT; 85 dB + 300 ppm). Oxidative stress was assessed by measuring malondialdehyde (MDA) levels and the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Renal function was evaluated using serum urea and creatinine levels, along with serum concentrations of the pro-inflammatory cytokines TNF-α and IL-1β. Histopathological analyses were performed to identify structural alterations in the kidneys. All exposed groups exhibited significant renal impairment, as indicated by elevated urea and creatinine levels. MDA levels were markedly increased, confirming oxidative stress. Noise exposure induced elevated SOD and CAT activities, whereas toluene exposure led to a reduction in these activities. Combined exposure exacerbated biochemical imbalances, elevated pro-inflammatory cytokine levels, and intensified renal tissue damage, including glomerular atrophy, tubular degeneration, vascular congestion, and leukocyte infiltration in the renal tissue. These findings demonstrate that toluene and noise are potent nephrotoxic agents whose co-exposure amplifies oxidative and inflammatory injuries. This highlights the critical need to consider combined environmental exposure in toxicological risk assessments.

Recent studies have highlighted the toxicological impact of nanoparticles, including their role in malignancies and various organ system dysfunctions, however, the effects of nanoparticles on the cardiovascular system remain underexplored. Their fore; this study designed to investigate the therapeutic effect of Curcumin (Cur) and/or Curcumin nanoparticles (CurNPs) against Copper oxide nanoparticles (CuONPs) induced toxicity, DNA damage, oxidative stress, apoptosis and inflammation in rat cardiac tissues. A total of 60 adult male rats were assigned randomly to 6 groups [1^st Gp, control; 2^nd Gp; Cur; 3^rd Gp, Cur NPs; 4^th Gp, CuONPs; 5^th Gp, CuONPs+Cur; 6^th Gp, CuONPs+CurNPs]. Current results revealed, a significant elevation in serum levels of creatine kinase enzyme (CK), lactate dehydrogenase (LDH), C-reactive proteins (CRP), AST, cholesterol, triglycerides, LDL, cardiac MDA, nitric oxide (NO), DNA damage, cardiac TNFα expressions and a significant decline in HDL, cardiac total antioxidant capacity (TAC), reduced glutathione (GSH), catalase, cardiac PCNA, Bcl2 expressions when compared to control. Interestingly, treatment of CuONPs with Cur or CurNPs induced improvements of the studied parameters, heart structure and functions. CuONPs-induced toxicity, injury and oxidative stress in rat heart and the treatment with CurNPs and Cur could scavenge free radicals producing beneficial effects against CuONPs.

In this study, zinc oxide nanoparticles (ZnONPs) were synthesized by green synthesis technique using the extract obtained from Sideritis akmanii plant and the obtained ZnONPs were characterized by Ultraviolet-Visible Spectrophotometry (UV-VIS), X-Ray Diffraction (XRD) spectrophotometer, Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FT-IR) techniques. Cytotoxic effects of both ZnONPs and Sideritis akmanii plant extract on A549 cells were investigated by MMT assay and genotoxic effects by Comet assay method. It was observed that the cytotoxic activity of ZnONP doses was higher than Sideritis akmanii plant extracts. In the comet test, the highest DNA damage (62.25 ± 10.15) was observed in the 10 mg/mL ZnONP application at 48 h of application, DNA damage did not exceed the negative control group at 3 different plant extract doses. Moreover, the genotoxic effects of 4 different concentrations of ZnONPs (0.1, 1, 5, 10 mM) were evaluated on Drosophila melonagaster with the SMART test. The results obtained as a result of ZnONP application were found to be close to the control group and it was determined that no statistically significant genotoxic effect was observed. The antimicrobial activity of ZnONPs on Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 29213), Salmonella enteritidis (ATCC 13076), Klebsiella pneumoniae (ATCC 700603) and Candida albicans (ATCC 90028) microorganisms was analyzed using disk diffusion method. According to the antimicrobial and antifungal activity data, it was determined that the synthesized ZnONPs were effective on all microorganism strains used in the study and the inhibition zone diameters ranged from 8 to 13.67 mm.

The pathogenesis of Alzheimer's disease remains incompletely understood. Methyl-4-hydroxybenzoic acid, a common chemical additive, may play a role, though its mechanisms are unclear. This research investigated the potential causal link between Methyl-4-hydroxybenzoic acid and Alzheimer's disease and examined underlying molecular mechanisms. Mendelian randomization analysis evaluated causality, using Cochran's Q test, the Mendelian Randomization-Egger intercept test, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier to assess heterogeneity and sensitivity. Methyl-4-hydroxybenzoic acid targets were identified through multiple databases, and a related target library was constructed using Weighted Gene Co-expression Network Analysis, differential gene expression analysis, and the Genecards database. A Protein-Protein Interaction network identified core genes, validated by molecular docking. Transcriptomic analysis and single-cell expression data explored cell-type-specific expression patterns. Results showed a significant positive causal association between Methyl-4-hydroxybenzoic acid and Alzheimer's disease. We identified 198 Methyl-4-hydroxybenzoic acid targets, with 99 genes associated with both Methyl-4-hydroxybenzoic acid and Alzheimer's disease. Six core genes (EGFR, ESR1, MAPK3, MMP9, PTGS2, TP53) were pinpointed. Functional enrichment implicated neuronal signaling, inflammation, and metabolism. Multi-omics and single-cell analyses revealed differential expression of core genes in key brain regions. Molecular docking confirmed stable interactions between Methyl-4-hydroxybenzoic acid and these proteins. This research confirms a causal relationship between Methyl-4-hydroxybenzoic acid and Alzheimer's disease, revealing potential molecular mechanisms and core gene functions, offering insights into pathogenesis and therapeutic targets.

The global population is aging rapidly, posing new challenges for the safety evaluation of chemicals. Most toxicity studies use suitably aged animals that resemble healthy adults if they have similar responses. However, this assumption may not be valid because aging affects various physiological functions, such as immunity. The objective of this study was to compare the skin sensitization potential of chemicals in healthy adult mice, aged mice, and an aging mouse model using local lymph node assays (LLNA). Initially, eight-week-old female CBA/Ca, C3H/He (historical control for SAMP1 mice), senescence-accelerated mouse prone 1 (SAMP1), and C57BL6/N mice were compared to verify any differences among these strains. Next, 20-wk-old C3H/He and SAMP1 mice were compared with 80-wk-old C57BL6/N mice. Several concentrations (2.76, 8.3, and 25%) of α-hexyl cinnamaldehyde (HCA) were used as a positive substance for LLNA to determine the skin sensitization potential in each strain. The proliferation of T and B cells and related cytokine production were also measured. A dose-dependent correlation was observed, and a threshold of 1.8 for positive criteria for skin sensitization in LLNA, was surpassed in the CBA/Ca, C3H/He, and C57BL6/N strains, but not in the SAMP1 strain. In 20-wk-old mice, a positive response was observed only in C3H/He mice, whereas no positive response was observed in aged C57BL6 mice and SAMP1 mice. Our findings imply that senescence affects the skin sensitization potential of chemicals as measured using LLNA.

This study was to investigate the effects of Albiflorin (ALB) on oxidative stress and inflammation in diabetic retinopathy (DR) and explore its potential mechanism involving the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway. Human retinal microvascular endothelial cells (HRMECs) were treated with high glucose (HG) and ALB. Cell viability was assessed by MTT assay. Oxidative stress markers and inflammatory cytokines were measured by ELISA. TLR4/NF-κB pathway proteins were analyzed by Western blot. A streptozotocin (STZ)-induced diabetic rat model was established to examine retinal histological changes. Serum metabolic parameters, oxidative stress markers, and inflammatory cytokines were evaluated in the DR model and ALB intervention groups. Results showed that ALB improved HRMEC viability under HG induction and reduced oxidative stress and inflammation. ALB inhibited the TLR4/NF-κB pathway in HG-induced HRMECs. Overexpression of TLR4 partially reversed the protective effects of ALB. In diabetic rats, ALB ameliorated metabolic disorders, improved retinal histological structure, and reduced oxidative stress and inflammation. ALB also suppressed the TLR4/NF-κB signaling pathway in vivo. In conclusion, ALB improves DR by resolving oxidative stress and inflammation through inhibiting the TLR4/NF-κB signaling pathway. These findings suggest ALB as a potential therapeutic agent for DR.