Toxicology Research最新文献

Background: Radon, a potent carcinogen, is a significant catalyst for lung cancer development. However, the molecular mechanisms triggering radon-induced lung cancer remain elusive.

Methods: Utilizing a radon exposure concentration of 20,000 Bq/m3 for 20 min/session, malignant transformation was induced in human bronchial epithelial cells (BEAS-2B).

Results: Radon-exposed cells derived from passage 25 (BEAS-2B-Rn) exhibited enhanced proliferation and increased colony formation. Analysis of differential gene expression (DEG) through transcription factors revealed 663 up-regulated and 894 down-regulated genes in radon-exposed cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed significant alterations in the malignant transformation pathway of cells, including those related to cancer and the PI3K/AKT signaling pathway. A PPI network analysis indicated a significant association of oncogenes, such as CCND1, KIT, and GATA3, with lung cancer among differentially expressed genes. In addition, the stability of the housekeeping gene was determined through RT-qPCR analysis, which also confirmed the results of transcriptome analysis.

Conclusions: The results suggest that transcription factors may play a pivotal role in conferring a survival advantage to radon-exposed cells. This is achieved by malignant transformation of human bronchial epithelial cells into lung carcinogenesis cell phenotypes.

Background: The tobacco epidemic signifies a major public health threat. Nicotine (NIC), a major active constituent in tobacco, impedes male fertility and semen quality. This work is implemented to explore the potential of selenium nanoparticles (SeNPs) and the newly fabricated SeNPs @vitamin C (SeNPs@VITC) nanocomposite in mitigating testicular toxicity induced by NIC.

Materials and methods: The six groups of 48 adult Wistar rats were designed as follows: the control group injected intraperitoneally with normal saline, the SeNPs group treated orally with 2 mg/kg of SeNPs, the SeNPs@VITC nanocomposite group treated orally with 2 mg/kg of SeNPs@VITC nanocomposite, the NIC group injected intraperitoneally with 1.25 mL/kg of NIC, the NIC+ SeNPs group received SeNPs plus NIC, and the NIC+ SeNPs@VITC nanocomposite group received SeNPs@VITC nanocomposite plus NIC. Treatments were administered over a 28-day period.

Results: NIC treatment significantly caused poor sperm quality, decreased serum testosterone, increased follicle-stimulating hormone (FSH), luteinizing hormone (LH) concentrations, reduced hemoglobin levels, leukocytosis, disrupted testicular oxidant/antioxidant balance, and disorganized testicular structure. The construction of the novel SeNPs@VITC nanocomposite, compared to NIC plus SeNPs alone, demonstrated a more potent ameliorative effect on NIC-induced reproductive toxicity in adult rats. The SeNPs@VITC nanocomposite significantly increased sperm count, reduced the percentage of sperm head abnormalities, lowered both serum FSH and LH concentrations, and improved the hemoglobin response.

Conclusions: Both SeNPs and SeNPs@VITC nanocomposite alleviated the testicular toxicity induced by NIC, but the SeNPs@VITC nanocomposite exhibited superior efficacy. The SeNPs@VITC nanocomposite could be employed to advance enhanced therapeutic strategies for addressing male infertility.

Background: There is growing concern of the potential damage to vital organs after long term exposure to locally formulated pesticides in rural area of Nigeria. This study was designed to assessed the effects of the individual chemical compound and their combination on the kidney and liver of rats' model.

Methodology: Fifty-four rats divided into six groups and three sub-groups were exposed to 25, 50 and 75% dose of each of the pesticide's LD₅₀ for 4 h at 3 days interval in an inhalation chamber for 28 days. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TOT_BIL), creatinine and urea assay showed significant increase at the aforementioned doses in comparison to the control group. The red blood cell counts, hematocrit and hemoglobin concentrations were significantly altered in the rats administered varying doses of the pesticides when compared with the control. Similar result was obtained for the differential white blood cell counts. Histopathological examinations of the liver tissue of rats showed infiltrated sinusoids, traces of karypyknosis, vacuolar degeneration and microvesicular steatosis while that of the renal tissue showed glomeruli atrophy leading to widened Bowman's spaces as well as few shrunken glomeruli and varied level of degenerative tubular changes to tubular necrosis.

Conclusion: This study established that individual pesticides and their mixture is toxic to the liver and kidney, as evidenced by the elevated markers of renal and liver functions and distortion of the structure of both organs as revealed by their photomicrographs. Therefore, it is a matter of public health significance to regularly monitor pesticide residues in foods and humans in order to assess the food safety risk and population exposure to pesticides.

The present study was performed to evaluate the therapeutic impact of Diospyros kaki fruit aqueous extract (DKFAE) on ethanol induced peptic ulcer. The phytochemical studies of DKFAE were investigated using colorometric analysis. Gastric ulcer was induced by one dose of ethanol (5 ml/Kg, b.w) on 24 h empty stomach. Then, the plant extract (200, 400 mg/kg) was orally administrated for 2 weeks. Famotidine (FAM: 40 mg/kg, b.w.): a reference drug was also tested. The effect of mixture dose between the fruit extract and FAM (DKFAE, 50 mg/kg PC, p.o. + FAM, 50 mg/kg PC, p.o.) was also evaluated. One hour after induction of ulcer blood samples were collected, stomach acidity and volume, as well as lesion counts were measured, then stomach and intestine of scarified rats were subjected to biochemical, macroscopic and microscopic studies. Results showed that DKFAE exhibited an important antioxidant potential. In vivo, the results showed that alcohol induced gastric damage, improving oxidative stress markers level such as MDA and H2O2, gastric and intestinal calcium and free iron. The intoxication by ethanol also produce an inflammation occurred by high level of the C-reactive protein (CRP) and alkaline phosphatase (ALP) activity in plasma. In contrast, DKFAE and the mixture dose significantly protect against macroscopic and histological injuries, the secretory profile disturbances, lipid peroxidation, antioxidant enzymes activities and non enzymatic antioxidant level decrease induced by ethanol administration. More impressively, the mixture dose exerted the more excellent effect than DKFAE and famotidine each alone showing is possible synergism.

Background: A growing number of findings have focused on the distinctive physiochemical characteristics that marine microorganisms have acquired as a result of their adaptation to the challenging conditions inherent in the marine environment. It has been established that the marine environment is a very rich source of bioactive substances with a variety of biological effects and structural diversity. A major discovery was the extraction of xyloketals from Xylaria sp. Numerous thorough studies have subsequently been carried out to determine the medicinal potential of these bioactive components. Xyloketals are thought to be a very promising and significant class of naturally occurring substances with a wide range of potent biological activities, such as radical scavenging, suppression of cell proliferation, reduction of neonatal hypoxic-ischemic brain injury, antioxidant activity, inhibition of acetylcholine esterase, inhibition of L-calcium channels, and others. Xyloketal B is one of the most potent molecules with significant therapeutic properties among the numerous variants discovered.

Conclusion: This review summarizes the structural characterization of all naturally occurring xyloketal compounds, especially the B derivative with an emphasis on their bioactivity and provides an outline of how xyloketals operate in diverse disease scenarios.

This study investigated the acute and repeated 28-day dose toxicity profiles of Bacillus clausii M31, isolated from children's feces, in Swiss rats and New Zealand rabbits. To investigate acute toxicity, rats were given varied doses of B. clausii M31 (1 × 10¹¹ CFU/mL, 3 × 10¹¹ CFU/mL, and 5 × 10¹¹ CFU/mL) orally once daily for 14 days, in accordance with OECD recommendations No. 423. To evaluate toxicity, rabbits were given either a low dosage (1 × 10¹¹ CFU/mL) or a high dose (5 × 10¹¹ CFU/mL) during a 28-day period using the OECD Test Guideline 407 protocol. Neither death nor significant abnormalities were observed in the rats during the experiment. The microscopic examination of key organs revealed no substantial changes in organ morphology. Furthermore, analyses of serum biochemistry and hematological parameters did not reveal any treatment-associated variations. In sum, these findings suggest that the oral intake of B. clausii M31 at concentrations up to 5 × 10¹¹ CFU/mL for 28 days poses no discernible risks.

Toxicological empirical research suggests that excessive utilization of paraquat, an herbicide, shows detrimental consequences on mammalian reproductive toxicity. The current study aims to study it as a reproductive toxin on the caprine testicular cells at 4- and 6-hour exposure duration. Paraquat treatment decreased the cell viability percentage and induced histological architectural alterations such as disruption of germinal epithelium, vacuolization, and pyknotic nuclei in the testis. The differential EB/AO staining also revealed an increased incidence of apoptosis after paraquat treatment at both dosages, i.e. 10 mM and 100 mM. Paraquat also induces oxidative stress, as evident via increased Malondialdehyde levels (a byproduct of lipid peroxidation) and a decline in the antioxidant capacity (FRAP). However, co-administration of Vitamin E significantly reduced the paraquat-mediated decline in cell viability percentage, histological alterations, and apoptosis incidences and generated oxidative stress, indicating its antioxidative properties against paraquat exposure. This research concludes that Vitamin E co-administration considerably reduced the toxicity of paraquat elicited in testicles, suggesting that Vitamin E may have advantageous potential in preventing the male gonadotoxicity caused by paraquat use in agriculture.

Introduction: The number of new diagnosed cancer cases and cancer deaths are increasing worldwide. Perfluorinated compounds (PFCs) are synthetic chemicals, which are possible inducers of cancer in human and laboratory animals. Studies showed that PFCs induce breast, prostate, kidney, liver and pancreas cancer by inducing genes being involved in carcinogenic pathways.

Methodology: This study reviews the association between PFCs induced up-regulation/down-regulation of genes and signaling pathways that are important in promoting different types of cancer. To obtain chemical-gene interactions, an advanced search was performed in the Comparative Toxicogenomics Database platform.

Results: Five most prevalent cancers were studied and the maps of their signaling pathways were drawn, and colored borders indicate significantly differentially expressed genes if there had been reports of alterations in expression in the presence of PFCs.

Conclusion: In general, PFCs are capable of inducing cancer in human via altering PPARα and PI3K pathways, evading apoptosis, inducing sustained angiogenesis, alterations in proliferation and blocking differentiation. However, more epidemiological data and mechanistic studies are needed to better understand the carcinogenic effects of PFCs in human.

Prunella vulgaris is widely used as the main ingredient of herb tea in Southeast Asia, as well as a traditional Chinese medicine. However, the heavy metal contaminations such as arsenic, cadmium, mercury and lead in P. vulgaris may be a cause for concern due to the environment pollution around, plantation and processing contamination. Thus, this study intented to assess both non-carcinogenic risks and carcinogenic risks attributed to cumulative exposure to the four heavy metals in P. vulgaris. The contaminations levels of heavy metals were determined in 90 batches of P. vulgaris. And the consumption level was obtained through a questionnaire survey among a total of 6,235 adult participants in Guangdong province. This study estimated the probabilistic health risks using Monte Carlo simulation, and found that the estimated mean and the 95th percentile values for cumulative noncarcinogenic risk (HI value) and carcinogenic risk (TCR value) of P. vulgaris were all within the acceptable risk. And the assessment results indicated that arsenic was the primary contributors to both noncarcinogenic and carcinogenic risks through P. vulgaris consumption. These findings and continuing the surveillance of heavy metals in P. vulgaris will be particularly relevant to both consumers and policy makers.

Paclitaxel (PCTX) is one of the most prevalently used chemotherapeutic agents. However, its use is currently beset with a host of problems: solubility issue, microplastic leaching, and drug resistance. Since drug discovery is challenging, we decided to focus on repurposing the drug itself by remedying its drawbacks and making it more effective. In this study, we have harnessed the aqueous solubility of sugars, and the high affinity of cancer cells for them, to entrap the hydrophobic PCTX within the hydrophilic shell of the carbohydrate β-cyclodextrin. We have characterized this novel drug formulation by testing its various physical and chemical parameters. Importantly, in all our in vitro assays, the conjugate performed better than the drug alone. We find that the conjugate is internalized by the cancer cells (A549) via caveolin 1-mediated endocytosis. Thereafter, it triggers apoptosis by inducing the formation of reactive oxygen species. Based on experiments on zebrafish larvae, the formulation displays lower toxicity compared to PCTX alone. Thus, our "Trojan Horse" approach, relying on minimal components and relatively faster formulation, enhances the anti-tumor potential of PCTX, while simultaneously making it more innocuous toward non-cancerous cells. The findings of this study have implications in the quest for the most cost-effective chemotherapeutic molecule.