Toxicology Research最新文献

Pollution of the aquatic environment with heavy metals is a serious environmental problem, since they accumulate in aquatic organisms and can affect their development and worsen their condition. According to the scheme of Fig. 1 zinc (Zn), copper (Cu) or lead (Pb) were studied when exposed to concentrations of: Zn (0.01; 0.1; 1 mg/L), Cu (0.001; 0.01; 0.1 mg/L), Pb (0.006; 0.06; 0.6 mg/L) for 144 h after fertilization (hpf) on the grass carp (Ctenopharyngodon idella), one of the important commercial fish species of Kazakhstan, the activity of superoxide dismutase (SOD) and the expression of genes of the Wnt/β-catenin signaling pathway involved in development. All metals significantly reduced survival, hatching rate, and changed biometric parameters and heart rate of cupid larvae. In addition, these metals (mainly Pb and Cu) inhibited superoxide dismutase (SOD) activity and mRNA transcription of genes encoding genes of the Wnt/β-catenin signaling pathway. These results showed that Pb, Cu and Zn not only affect the survival and development of fish at an early stage of life, but also cause oxidative stress and prevent fish detoxification.

Several studies showed the adverse effects of amoxicillin on various body organs. So, this research has been designed to evaluate the modulatory role of Ashwagandha seed extract (ASE) against amoxicillin (AM) toxicity. Rats treated with AM (90 mg/kg), protected by ASE doses (100, 200 and 300 mg/kg), and treated by ASE at the same three doses. At the end of the experimental period, DNA comet assay, cytogenetic examinations, sperm-shape analysis, evaluation of the malondialdehyde (MDA) percentages, histopathological examinations, and biophysical tests (modulus, relaxation time, permittivity, entropy, and internal energy change of brain) were documented. The results confirmed that AM treatment induced significant elevation of DNA damage, cytogenetic aberrations, and MDA content in brain, liver, and testis tissues and sperm-shape anomalies. ASE treatment significantly minimized the genetic changes, sperm-shape anomalies, and MDA generation. These enhancements were more pronounced by protective ASE and increased by increasing the dose level. In histopathological examinations, AM treatment caused neurotoxicity in brain tissue. ASE treatment, partially, minimized these damages and the positive effects of therapeutic ASE were more noticeable. Biophysical parameters showed that therapeutic ASE was better for relaxation time, permittivity, and free energy change. Protective and therapeutic ASE were able to recover entropy and internal energy changes in variant degrees.

Background: Organophosphorus compounds, widely used in agriculture and industry, pose a serious threat to human health due to their acute neurotoxicity. Although traditional interventions for organophosphate poisoning are effective, they often come with significant side effects.

Objective: This paper aims to evaluate the potential of enzymes within biological organisms as organophosphorus bioclearing agents. It analyses the technical challenges in current enzyme research, such as substrate specificity, stereoselectivity, and immunogenicity, while exploring recent advancements in the field.

Methods: A comprehensive review of literature related to detoxifying enzymes or proteins was conducted. Existing studies on organophosphorus bioclearing agents were summarised, elucidating the biological detoxification mechanisms, with a particular focus on advancements in protein engineering and novel delivery methods.

Results: Current bioclearing agents can be categorised into stoichiometric and catalytic bioclearing agents, both of which have shown some success in preventing organophosphate poisoning. Technological advancements have significantly improved various properties of bioclearing agents, yet challenges remain, particularly in substrate specificity, stereoselectivity, and immunogenicity. Future research will focus on expanding the substrate spectrum, enhancing catalytic efficiency, prolonging in vivo half-life, and developing convenient administration methods.

Conclusion: With the progression of clinical trials, bioclearing agents are expected to become widely used as a new generation of therapeutic organophosphate detoxifiers.

Introduction: There is a significant shortage of observational studies on neurotoxic snakebite envenomation in the Philippines. This lack of data, especially concerning treatment using Purified Cobra Antivenom (PCAV), has prompted the initiation of this foundational study.

Methods: The target population included snakebite patients admitted to the Eastern Visayas Medical Center and treated with PCAV between 2016 and 2020. A retrospective chart review was conducted for data collection. The investigation analyzed the hospital stay and patient features of individuals who were administered either lower or higher doses of PCAV.

Results: Eighty-two patients were identified during the study. Of these, 27 (33%) were under 20 years of age and 50 (61%) were male. Most patients, totalling 75 (92%) were hailed from rural areas. Of the 82 patients, 59 (72%) received one or two ampoules of PCAV during the course. However, patients who received more than two ampoules had a longer median hospital stay than those who received less than three ampoules [96 h (interquartile range, IQR 66-122) vs. 125 h (IQR 96-218), P = 0.038]. The study reported five in-hospital mortalities (6.1%).

Conclusions: The individuals who needed a high dosage of PCAV tended to have more extended hospital stays, yet over 70% of the patient population required a lower dosage. To gain a clearer understanding of the burden of neurotoxic snakebites and determine the optimal PCAV dosage based on disease severity in the area, a more comprehensive, prospective study is recommended.

Background: Corylin, a natural flavonoid, is isolated from the fruit of Psoralea corylifolia L. Nevertheless, the effect of corylin on sepsis-associated cardiac dysfunction is still unclear. The purpose of this study is to determine the role and mechanism of corylin in sepsis related cardiac dysfunction.

Methods: Experiments were carried out on mice with lipopolysaccharide (LPS) or sepsis induced by cecal ligation and puncture (CLP) or myocardial cell sepsis induced by LPS.

Results: Administration of corylin improved cardiac dysfunction induced by LPS or CLP in mice. Corylin inhibited the increases of interleukin-1 (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in the heart of mice with LPS or CLP. LPS elevated the levels of IL-1β, IL-6 and TNF-α in cardiomyocytes, which were inhibited by corylin treatment. Corylin attenuated the increases of microRNA (miRNA)-214-5p in the heart of mice with LPS, CLP, LPS-treated NRCMs, H9c2 and AC16 cells. Administration of miRNA-214-5p agomiR reversed the improving effects of corylin on the damaged cardiac function and the increases of IL-1β, IL-6 and TNF-α in mice treated with LPS.

Conclusion: These outcomes indicated that corylin improved sepsis-associated cardiac dysfunction by inhibiting inflammation. And corylin inhibited inflammation of sepsis by decreasing miRNA-214-5p. Downregulation of miRNA-214-5p improved sepsis-associated cardiac dysfunction and inhibited inflammatory factors.

Zebrafish being the best animal model to study, every attempt has been made to decipher the toxic mechanism of every fungicide of usage and interest. It is important to understand the multiple targets of a toxicant to estimate the toxic potential in its totality. A total of 22 fungicides of different classes like amisulbrom, azoxystrobin, carbendazim, carboxin, chlorothalonil, difenoconazole, etridiazole, flusilazole, fluxapyroxad, hexaconazole, kresoxim methyl, mancozeb, myclobutanil, prochloraz, propiconazole, propineb, pyraclostrobin, tebuconazole, thiophanate-methyl, thiram, trifloxystrobin and ziram were reviewed and analyzed for their multiple explored targets in zebrafish. Toxic end points in zebrafish are highly informative when it comes to network analysis. They provide a window into the molecular and cellular pathways that are affected by a certain toxin. This can then be used to gain insights into the underlying mechanisms of toxicity and to draw conclusions on the potential of a particular compound to induce toxicity. This knowledge can then be used to inform decisions about drug development, environmental regulation, and other areas of research. In addition, the use of zebrafish toxic end points can also be used to better understand the effects of environmental pollutants on ecosystems. By understanding the pathways affected by a given toxin, researchers can determine how pollutants may interact with the environment and how this could lead to health or environmental impacts.

Introduction: Cadmium (Cd) has been shown to disrupt the reproductive system. In this study, we evaluated the protective effects of Curcumin (Cur) against Cd-induced reproductive toxicity.

Methods: Exploring the role of Cur in Cd-treated rat models.

Results: The study demonstrated that Cd treatment impaired the seminiferous epithelium, leading to increased apoptosis of germ cells. Interestingly, pretreatment with Cur ameliorated the histological damage and decreased the germ cell apoptosis induced by Cd. Furthermore, after Cd exposure, B-cell lymphoma-2 expression was significantly decreased while Bax expression was increased. Pretreatment of rats with Cur protected against germ cell apoptosis by improving the expression of B-cell lymphoma-2 and reducing Bax. Additionally, Cd treatment increased reactive oxygen species, resulting in a decrease in antioxidant enzymes. However, pretreatment of rats with Cur followed by Cd administration led to a substantial decrease in reactive oxygen species levels and increased activities of antioxidant enzymes. Ultrastructural investigations revealed that damage to the mitochondrial structure was significantly ameliorated by Cur pretreatment in Cd-treated rats. Notably, Cur significantly activated the peroxisome proliferator-activated receptor gamma coactivator 1a/Sirtuins-3 signaling pathway.

Conclusions: Overall, our data suggest that Cd induces germ cell apoptosis through mitochondrial-induced oxidative stress, but Cur pretreatment offers strong protection against Cd-induced reproductive toxicity.

Background: Skin secretions of toads are widely used in medicine all over the world for their antiviral, anti-infective, and cardiotonic properties. Because these secretions are mostly employed to combat blood parasite infection, it is important to understand their potential toxic effects on human erythrocytes. Therefore, the objective of the current investigation was to elucidate the effects of Duttaphrynus melanostictus (Schneider) skin extracts on the physiology of human erythrocytes.

Methods: Toads captured from their natural habitat were separated into three groups according to their body size. Hydroalcoholic extracts of toad skin were prepared by reflux heating. These extracts were then evaluated for their hemolytic and hemoglobin denaturation potential. The effects of the extracts on cytosolic and membrane-bound enzymes of human erythrocytes were assessed.

Results: The hemolysis and hemoglobin denaturation caused by these extracts correlated positively with the respective toad sizes. Extracts from medium and large toads led to increased osmotic fragility even at near iso-osmotic concentrations. Biochemical analysis of hemolysate showed that the treatment induced a shift of metabolic flux toward the glutathione pathway. Analysis of membrane-bound enzymes revealed a significant decrease in the activity of Na+/K+ ATPase and acetylcholinesterase. SDS-PAGE analysis of the erythrocyte membrane did not show the band of tropomodulin for the cells treated with 1000 𝜇g/ml extract from large toads.

Conclusions: In conclusion, the present study demonstrates that the toxicity of toad skin secretions aggravates with the size of the animal and interferes with the physiology of human erythrocytes, leading to their membrane disruption and rapid lysis.

Introduction: The rapid development of nanotechnologies with their widespread prosperities has advanced concerns regarding potential health hazards of the Nanoparticles.

Results: Nanoparticles are currently present in several consumer products, including medications, food, textiles, sports equipment, and electrical components. Despite the advantages of Nanoparticles, their potential toxicity has negative impact on human health, particularly on reproductive health.

Conclusions: The impact of various NPs on reproductive system function is yet to be determined. Additional research is required to study the potential toxicity of various Nanoparticles on reproductive health. The primary objective of this review is to unravel the toxic effects of different Nanoparticles on the human reproductive functions and recent investigations on the reproductive toxicity of Nanoparticles both in vitro and in vivo.

Background: Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus (DM), being the second cause of end-stage renal disease globally. Podocyte injury is closely associated with DN developmen. Our study aimed to investigate the role of long non-coding RNA (lncRNA) TTN-AS1 in DN-associated podocyte injury.

Methods: The mouse podocyte cell line (MPC5) and human primary podocytes were stimulated by high glucose (HG; 30 nM glucose) to establish the cellular model of DN. Before HG stimulation, both podocytes were transfected with sh-TTN-AS1#1/2 or pcDNA3.1/STAT3 to evaluate the influence of TTN-AS1 knockdown or STAT3 overexpression on HG-induced podocyte injury. TTN-AS1 and STAT3 expression in both podocytes was examined by RT-qPCR. Cell viability and death were assessed by CCK-8 and LDH release assay. ELISA was adopted for testing IL-6 and TNF-α contents in cell supernatants. The levels of oxidative stress markers (ROS, MDA, SOD, and GSH) in cell supernatants were determined by commercial kits. Western blotting was used for measuring the expression of fibrosis markers (fibronectin and α-SMA and podocyte function markers (podocin and nephrin) in podocytes.

Results: HG stimulation led to decreased cell viability, increased cell death, fibrosis, inflammation, cell dysfunction and oxidative stress in podocytes. However, knockdown of TTN-AS1 ameliorated HG-induced podocyte injury. Mechanically, the transcription factor STAT3 interacted with TTN-AS1 promoter and upregulated TTN-AS1 expression. STAT3 overexpression offset the protective effect of TTN-AS1 silencing on HG-induced podocyte damage.

Conclusion: Overall, STAT3-mediated upregulation of lncRNA TTN-AS1 could exacerbate podocyte injury in DN through suppressing inflammation and oxidative stress.