Environmental Toxicology最新文献

Cardiovascular disease is one of the leading causes of death worldwide and has a high prevalence. Insulin-like growth factor-II receptor α (IGF-IIRα) acts as a stress-inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF-IIRα in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)-induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF-IIRα and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF-IIRα overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy-related and inflammation-related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF-IIRα also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS-treated H9c2 cardiac myoblasts with IGF-IIRα overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis-related cardiac mechanisms. Our study suggests that under sepsis-like conditions in the heart with IGF-IIRα overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF-IIRα and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function.

Oxidative stress is a pivotal factor in the pathogenesis of various cardiovascular diseases. Rhodiola, a traditional Chinese medicine, is recognized for its potent antioxidant properties. Salidroside, a phenylpropanoid glycoside derived from Rhodiola rosea, has shown remarkable antioxidant capabilities. This study aimed to elucidate the potential protective mechanisms of Rhodiola and salidroside against H₂O₂-induced cardiac apoptosis in H9c2 cardiomyoblast cells. H9c2 cells were exposed to H₂O₂ for 4 h, and subsequently treated with Rhodiola or salidroside for 24 h. Cell viability and apoptotic pathways were assessed. The involvement of insulin-like growth factor 1 receptor (IGF1R) and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) were investigated. H₂O₂ (100 μM) exposure significantly induced cardiac apoptosis in H9c2 cells. However, treatment with Rhodiola (12.5, 25, and 50 μg/mL) and salidroside (0.1, 1, and 10 nM) effectively attenuated H₂O₂-induced cytotoxicity and apoptosis. This protective effect was associated with IGF1R-activated phosphorylation of ERK1/2, leading to the inhibition of Fas-dependent proteins, HIF-1α, Bax, and Bak expression in H9c2 cells. The images from hematoxylin and eosin staining and immunofluorescence assays also revealed the protective effects of Rhodiola and salidroside in H9c2 cells against oxidative damage. Our findings suggest that Rhodiola and salidroside possess antioxidative properties that mitigate H₂O₂-induced apoptosis in H9c2 cells. The protective mechanisms involve the activation of IGF1R and subsequent phosphorylation of ERK1/2. These results propose Rhodiola and salidroside as potential therapeutic agents for cardiomyocyte cytotoxicity and apoptosis induced by oxidative stress in heart diseases. Future studies may explore their clinical applications in cardiac health.

In patients with chronic kidney disease, the uremic toxin indoxyl sulfate (IS) accelerates kidney damage and the progression of cardiovascular disease. IS may contribute to vascular diseases by inducing inflammation in endothelial cells. Luteolin has documented antioxidant and anti-inflammatory properties. This study aimed to investigate the effect of luteolin on IS-mediated reactive oxygen species (ROS) production and intercellular adhesion molecule (ICAM-1) and monocyte chemoattractant protein (MCP-1) expression in EA.hy926 cells and the possible mechanisms involved. IS significantly induced ROS production (by 6.03-fold, p < 0.05), ICAM-1 (by 2.19-fold, p < 0.05) and MCP-1 protein expression (by 2.18-fold, p < 0.05), and HL-60 cell adhesion (by 31%, p < 0.05), whereas, luteolin significantly decreased IS-induced ROS production, ICAM-1 and MCP-1 protein expression, and HL-60 cell adhesion. Moreover, luteolin attenuated IS-induced nuclear accumulation of p65 and c-jun. Luteolin dose-dependently increased heme oxygenase-1 (HO-1) expression and the maximum fold induction of HO-1 by luteolin was 3.68-fold (p < 0.05), whereas, HO-1 knockdown abolished the suppression of ICAM-1 and MCP-1 expression by luteolin. Luteolin may protect against IS-induced vessel damage by inducing HO-1 expression in vascular endothelial cells, which suppresses nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) mediated ICAM-1 and MCP-1 expression.

Aluminum oxide nanoparticles (Al₂O₃ NPs) are among the most extensively utilized nanoparticles in nanotechnology and that have negative impacts on the environment. Therefore, the intention of this work is to investigate the protective and therapeutic effects of curcumin in nanoform (Cur NPs) against Al₂O₃ NPs induced kidney toxicity, oxidative stress, DNA damage, and changes in necrosis factor alpha (TNFα) and proliferating cell nuclear antigen (PCNA) expressions in male rats. Fifty healthy adult male were divided into five groups [G1, control; G2, received 50 mg/kg/day for 4 weeks of Cur NPs orally; G3, received 6 mg/kg BW orally for 4 weeks of Al₂O₃ NPs; G4, (Cur NPs + Al₂O₃ NPs) received Cur NPs and Al₂O₃ NPs at a dose similar to G2 and G3, respectively for 4 weeks; G5, (Al₂O₃ NPs + Cur NPs) received Al₂O₃ NPs at a dose similar to G3 for 4 weeks then received Cur NPs at a dose similar to G2 for another 4 weeks]. Current results revealed that Al₂O₃ NPs induced a significant elevation in serum urea, creatinine, chloride, calcium, kidney malondialdehyde (MDA), DNA damage, injury, TNFα and PCNA expressions and a significant depletion in serum potassium, kidney superoxide dismutase (SOD), glutathione (GSH) as compared to control. On the other hand, treatments of Al₂O₃ NPs with Cur NPs induced modulation in all altered parameters and improved kidney functions and structure, with best results for the Al₂O₃ NPs + Cur NPs than Cur NPs + Al₂O₃ NPs. In conclusion, Cur NPs has the capacity to mitigate the renal toxicity induced by Al₂O₃ NPs in male albino rats.

Cadmium, a heavy metal, disrupts cellular homeostasis and is highly toxic, with no effective treatments currently available against its toxicity. According to studies, phytochemicals provide a promising strategy for mitigating cadmium toxicity. Naringenin (NG), a potent antioxidant found primarily in citrus fruits, showed protective properties against cadmium toxicity in rats. Nonetheless, the precise mechanism of cadmium cytotoxicity in fibroblasts remains unknown. This study evaluated NG against cadmium (CdCl₂) toxicity utilizing network pharmacology and in silico molecular docking, and was further validated experimentally in rat fibroblast F111 cells. Using network pharmacology, 25 possible targets, including the top 10 targets of NG against cadmium, were identified. Molecular docking of interleukin 6 (IL6), the top potential target with NG, showed robust binding with an inhibition constant (Ki) of 58.76 μM, supporting its potential therapeutic potential. Pathway enrichment analysis suggested that “response to reactive oxygen species” and “negative regulation of small molecules metabolic process” were the topmost pathways targeted by NG against cadmium. In vitro analysis showed that NG (10 μM) attenuated CdCl₂-induced oxidative stress by reducing altered intracellular ROS, mitochondrial mass, and membrane potential. Also, NG reversed CdCl₂-mediated nuclear damage, G2/M phase arrest, and apoptosis. GC/MS-based metabolomics of F111 cells revealed CdCl₂ reduced cholesterol levels, which led to alterations in primary bile acid, steroid and steroid hormone biosynthesis pathways, whereas, NG restored these alterations. In summary, combined in silico and in vitro analysis suggested that NG protected cells from CdCl₂ toxicity by mitigating oxidative stress and metabolic pathway alterations, providing a comprehensive understanding of its protective mechanisms against cadmium-induced toxicity.

Military personnel, firefighters, and fire survivors exhibit a higher prevalence of mental health conditions such as depression and post-traumatic stress disorder (PTSD) compared to the general population. While numerous studies have examined the neurological impacts of physical trauma and psychological stress, research on acute neurobehavioral effects of gas inhalation from explosions or fires is limited. This study investigates the early-stage neurobehavioral and neuronal consequences of acute explosion gas inhalation in Sprague–Dawley rats. Rats were exposed to simulated explosive gas and subsequently assessed using behavioral tests and neurobiological analyses. The high-dose exposure group demonstrated significant depression-like behaviors, including reduced mobility and exploration. However, neuronal damage was not evident in histological analyses. Immunofluorescence revealed increased density of radial glia and oligodendrocytes in specific brain regions, suggesting hypoxia and axon damage induced by gas inhalation as a potential mechanism for the observed neurobehavioral changes. These findings underscore the acute impact of explosion gas inhalation on mental health, highlighting the habenula and dentate gyrus of hippocampus as the possible target regions. The findings are expected to support early diagnosis and treatment strategies for brain injuries caused by explosion gas, offering insights into early intervention for depression and PTSD in affected populations.

The health risks associated with microplastics have attracted widespread attention. Polystyrene microplastics (PS-MPs) can induce damage to cardiac tissue, while pyroptosis-mediated injury to the vascular endothelial plays a vital role in the pathogenesis of cardiovascular diseases. The study intended to explore the role and mechanism of NLR family pyrin domain containing 3 (NLRP3) mediated pyroptosis in PS-MPs causing the injury of vascular endothelial cells. In vivo, Wistar rats were exposed to 0.5, 5, and 50 mg/kg/d 0.5 μm PS-MPs. In vitro, the human vascular endothelial cells (HUVECs) were used for mechanistic studies. siRNA was used for silencing the NILRP3 gene. H&E staining and flow cytometry were performed to examine the vascular injury and cell membrane damage. The oxidative stress was detected by flow cytometry, immunofluorescence, and corresponding kits. ELISA were used to measure the levels of inflammatory factors. Real-time PCR and western blot were used to measure the expression of pyroptosis signaling pathway. In rats, PS-MPs could cause vascular damage, oxidative stress, and inflammatory response, and activated the pyroptosis signaling pathway. HUVECs exposure to PS-MPs, the vitality decreased in a dose-dependent manner, ROS and MDA were significantly increased while SOD was decreased. PS-MPs induced the onset of pyroptosis signaling pathway in HUVECs. Cell membrane damage and the levels of IL-Iβ and IL-18 in HUVECs significantly increased, those are symbols for the development of pyroptosis. Inhibition of NLRP3-mediated pyroptosis effectively protected HUVECs from PS-MPs-induced damage. Pyroptosis played a vital role in controlling the vascular endothelial injury caused by PS-MPs.

Acrylamide (AAM), a compound extensively utilized in various industrial applications, has been reported to induce toxic effects across multiple tissues in living organisms. Despite its widespread use, the impact of AAM on ovarian function and the mechanisms underlying these effects remain poorly understood. Here, we established an AAM-exposed mouse toxicological model using 21 days of intragastric AAM administration. AAM exposure decreased ovarian coefficient and impaired follicle development. Further investigations revealed AAM would trigger apoptosis and disturb tricarboxylic acid cycle in ovarian tissue, thus affecting mitochondrial electron transport function. Moreover, AAM exposure decreased oocyte and embryo development potential, mechanically associated with pericentrin and phosphorylated Aurora A cluster failure, leading to meiotic spindle assembly defects. Collectively, these results suggest that AAM exposure may lead to apoptosis, glucose metabolic disorders, and mitochondrial dysfunction in ovary tissue, ultimately compromising oocyte quality.