Toxicology Research最新文献

Fertility control of rodents offers a promising alternative strategy, providing a long-term solution by gradually reducing the rodent population through controlled reproduction. Quinestrol, a synthetic estrogen, can potentially mitigate rodent fertility, but its lower bioavailability in the body limits its effectiveness. In this study, we prepared polymeric nanoparticles using standard polymer-based encapsulation techniques. This study aims to formulate, characterize, and evaluate quinestrol-based poly (lactic-co-glycolic acid) (PLGA) nanoparticles to enhance the bioavailability and contraceptive efficacy of quinestrol in rodents over extended periods. Blank PLGA nanoparticles (PNP) and those loaded with quinestrol (QNP) were successfully formulated using the emulsion-evaporation method and characterized for size, zeta potential, release kinetics and stability. The study further evaluated the toxicological impact of these nanoparticles on reproductive hormones in female rats (Bandicota bengalensis), measured using ELISA, and administered orally through cereal-based ready-to-use baits containing bulk quinestrol (QB-B) and QNP (QNP-B). Successful encapsulation yielded QNP (337.93 ± 6.51 nm), smaller than PNP (354.33 ± 3.87 nm), with a 13.42% drug loading. Low PDI (<0.3) confirmed uniform size. Drug release involved an initial burst followed by slow release up to 96 h. Quinestrol in both QNP-B (10 ppm) and QB-B (100 ppm) increased estradiol (11.59 to 32.38-41.13 pg/mL) and progesterone (4.70 to 14.42-18.25 ng/mL), while reducing FSH (0.94 to 0.42-0.45 mIU/mL) and LH (28.15 to 17.60-18.69 mIU/mL) after 15 days. QNP-B effects lasted 75 days, compared to 45 days for QB-B, demonstrating the prolonged efficacy of QNP and supporting PLGA-based delivery as a promising approach for sustained rodent fertility control.

This review synthesizes in silico evidence on the toxicological effects of microplastics (MPs) and nanoplastics (NPs) in zebrafish (Danio rerio). With the increasing prevalence of these pollutants in aquatic ecosystems, evaluating their molecular impacts is essential for risk assessment. We systematically mined toxicogenomic studies from PubMed, Scopus, and Web of Science and applied network biology approaches to identify gene-gene interactions underlying micro- and nanoplastic (MNP) toxicity. Using STRING for protein-protein interaction mapping and Cytoscape with cytoHubba for hub-gene detection, we identified casp3a, casp3b, bcl2a, tp53, and nfe2l2a as central regulators of stress responses. Enrichment analyses linked these genes to oxidative stress, apoptosis, inflammatory signalling, and transcriptional dysregulation, pathways implicated in cardiotoxic, neurotoxic, reproductive, and developmental outcomes. While zebrafish provide a relevant vertebrate model, the present findings are derived exclusively from computational analyses and require experimental validation. By integrating toxicogenomics with network-based approaches, this review provides mechanistic insights into MNP-induced perturbations in zebrafish and highlights molecular pathways that may mediate broader ecological and human health risks.

Oligospermia is a severe disorder that affects the male population around the world. Genetic defects, smoking, age, and modern lifestyle are significant contributing factors to male infertility in oligospermia. Myrica esculenta fruits contain high levels of chlorogenic acid, caffeic acid, myricetin, quercetin, and ascorbic acid, which have antioxidant, anti-inflammatory, and pharmacological properties. Therefore, the present study evaluates the protective effects of Myrica esculenta aqueous extract against cyclophosphamide (CYP)-induced spermatogenic dysfunction in rats. A total of 25 Wistar rats were divided into five groups, each group consisting of 5 animals; 1) normal control (saline 5 mL/kg), 2) CYP (30 mg/kg, i.p.), 3) clomiphene citrate (0.25 mg/kg/i.p.), 4) aqueous Manihot esculenta extract (250 mg/kg/p.o.), 5) aqueous M. esculenta extract (500 mg/kg/p.o.). Treatment was given once a day for 15 days continuously. Our observation found a significant improvement in total sperm count, viability, motility, and a decline in abnormal sperm generation in M. esculenta extract 250 and 500 mg/kg treatment groups as compared to CYP-treated Wistar rats. Moreover, M. esculenta extract shows a significant increase in the 3β-HSD, 17β-HSD, GSH, and catalase, and reduces the oxidative stress, thereby improving the sperm quality. M. esculenta extract was found to reduce DNA fragmentation and restore the testicular composition by enhancing the number of spermatogonia and Sertoli cells in test-treated rats as compared to disease control rats. M. esculenta extract also improved sperm quality, boosted testosterone, and reduced oxidative stress, protecting against oligospermia. These findings highlight its therapeutic potential in managing male infertility. However, further investigations are necessary to elucidate the precise molecular mechanisms underlying its protective effects.

Diethylhexyl phthalate (DEHP) as a common environmental pollutant has toxic effects on a variety of biological systems, including liver toxicity and immunotoxicity. Previously we had demonstrated that DEHP cause cholestatic liver injury, but whether macrophages play a role in this is unclear, and few studies have focused on the direct effects of DEHP on macrophages. Therefore, this study investigated whether DEHP affects macrophages in vivo and the mechanism by which DEHP regulates macrophages in vitro. The results showed that DEHP induced cholestatic liver injury by up-regulating TBA levels of serum and liver. Simultaneously, DEHP increased the number of F4/80 positive macrophages and promoted the transcriptional level of IL-1β and IL-6 in liver tissue. Further in vitro, We found that DEHP decreased M2 macrophage marker Arg1 level and increased the levels of M1 macrophage marker iNOS, accompanied by up-regulation of the transcriptional levels of IL-1β, TNF-α and CCl₂. Moreover, DEHP increased glycolytic flux, which was confirmed by the increased Glut1, HK2 and pfkfb3 expression. Mechanistically, we found DEHP inhibited NRF2 activation, and down-regulated the expression of downstream target NOQ1. While, CDDO (an NRF2 activator) could abrogate the promotion of DEHP on M1 macrophage polarization and glycolysis. These findings indicated that promotion effect of DEHP on M1 macrophage polarization is associated with regulating energy metabolism of macrophages through NRF2/NQO1 pathway.

Aluminum (Al) is a widely accessible environmental and industrial element that finds routes of exposure through inhalation of airborne particles, ingestion of contaminated food and water, dermal and medical applications. Chronic and acute exposure lead to systemic accumulation of Al that induce aluminum toxicity. Exposure to Al exerts diverse toxicological effects, including oxidative stress, immune dysregulation, genotoxicity, pro-inflammatory activity, protein misfolding, enzymatic inhibition, metabolic imbalance, membrane dysfunction and induction of apoptosis and necrosis. The Al toxicity is associated with a wide range of pathologies such as respiratory diseases, cardiovascular complications, gastrointestinal disorders, inflammation, hematologic, hepato-renal and neurodegenerative diseases and reproductive and developmental disorders, genotoxicity as well as endocrine and pancreatic necrosis. This comprehensive review narrates multifactorial nature of Al toxicity emphasizing role of reactive oxygen species in pathogenesis and significances of Al exposure in high-risk populations.

The current research aims to map the spatial distribution of potentially toxic elements (PTEs) (As, Co, Cr, Cu, Fe, Mn, Ni, V, and Zn) in Qena southern of Egypt, identify the sources of PTEs using geostatistical analysis (principal component analysis, cluster analysis, and correlation matrix(, and determine the level of contamination in the study area to assess soil contamination with selected potentially toxic elements. To accomplish this, thirty soil samples were gathered and examined for the PTEs. The variability of the soil chemical content was estimated using multivariate geostatistical analysis. All PTEs, with the exception of As, show a strong positive association with one another in the correlation matrix. Two components illustrated through the principal component analysis (PCA). The primary source of the first component, which accounts for the majority of the variance, is a combination of industrial activity and agricultural activities. It is rich in Co, Cr, Cu, Fe, Mn, Ni, V, and Zn. As is abundant in the second component, and lithology may be the source. According to the Pollution Load Index (PLI), 61% of the study area (west and south of the study area) was contaminated, and 31% of the study area (east of the study area) was unpolluted. The Degree of Contamination (DC) index was used to classify the research region as low, moderate, and considerably contaminated, with percentages of 21, 51, and 28% of the study area, respectively. The Nemerow Pollution Index (NPI) classifies the majority of samples (63.33%) as slightly to moderately polluted. The study's conclusions showed that to evaluate the potential risk to the environment, PTEs concentrations in the study area need to be monitored. This study aligns with key UN Sustainable Development Goals (SDGs), particularly SDG 3 (Good Health) and SDG 15 (Life on Land), by to safeguarding both human well-being and terrestrial ecosystem health. Moreover, the study provides a scientific basis for sustainable environmental management, supporting the transition towards safer and more resilient communities.

Indoxacarb (IND) is a toxic pesticide that can cause several organ damages in non-target organisms. However, to date no study has investigated the impacts of IND on hepatic tissues at various concentrations. Therefore, this investigation was executed to evaluate the dose-dependent effect of IND on hepatic tissue. Albino rats (Rattus norvegicus) (n = 36) were divided into four groups: control and three IND concentrations (30, 60, and 90 mg/kg). IND exposure showed a notable reduction in the gene expression of Estrogen-Related Receptor Alpha (ERRα), nuclear respiratory factor-1 (NRF-1), mitochondrial transcription factor-A (TFAM), peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α), nuclear respiratory factor-2 (Nrf-2), and silent information regulator sirtuin-1 (SIRT1) while increasing the expression of adenosine monophosphate-activated protein kinase (AMPK). Moreover, IND exposure decreased the activities of catalase (CAT), heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione reductase (GSR) while increasing the levels of ROS and MDA. However, an increase was recorded in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) whereas the levels of albumin and total proteins were decreased after high dose (90 mg/kg) of IND. IND concentration (30, 60, and 90 mg/kg) induced apoptosis by increasing the levels of Bax, Caspase-9 and Caspase-3 while diminishing the levels of Bcl-2 and displayed adverse impacts on hepatic histological profile. In conclusion, the IND administration at all the tested doses cause severe hepatic damage via dysregulation of AMPK/SIRT1/NRF-2/ERRα, increasing oxidative stress, decreasing antioxidant defense, leading to inflammation, apoptosis and changes in the hepatic histology.

Methotrexate, used in the treatment of various cancers, induce oxidative stress, inflammatory response, apoptotic cell death and ultimately toxic lung damage when used for a long time or in excessive doses. Prevention of overproduction of reactive oxygen species and maintenance of cellular redox balance can be facilitated by the use of various natural antioxidants and essential oils. The aim of this study was to investigate the protective role of Alpha Pinene, a plant component known to have antioxidant, anti-inflammatory and cytoprotective properties, against Methotrexate-induced lung damage in rats. For this purpose, 35 adult male rats were randomly divided into 5 groups as Control, Vehicle, Methotrexate (20 mg/kg, single dose), Alpha Pinene (50 mg/kg/day) and Methotrexate+Alpha Pinene. At the end of the 14-day experimental period, the removed lungs were first weighed, then oxidative stress (superoxide dismutase, catalase and malondialdehyde) and apoptosis (APAF-1 and Caspase-3) parameters were measured, then the Heat Shock Protein 70 levels were determined, and finally Haematoxylin-Eosin and Masson's Trichrome stains were performed to evaluate histologic tissue damage. The data obtained revealed that Alpha Pinene significantly reduced Methotrexate induced changes in the oxidative stress and apoptosis parameters and Heat Shock Protein 70 levels. It was also shown to have a protective effect on the lungs against acute Methotrexate toxicity, preventing alveolar epithelial damage, congestion, inflammatory cell infiltration and alveolar degeneration despite the presence of mild fibrosis and interstitial edema. Alpha Pinene can be considered to be a highly valuable protective agent against Methotrexate-induced lung injury.