Initial evidence that formaldehyde triggers DAMP-associated sterile inflammation with disruption of metabolism and reproduction is provided and the potential benefit of quercetin treatment as a nutraceutical against environmental aldehydes by suppressing multitarget pathways is demonstrated.
T-2 toxin is a prevalent mycotoxin that poses a substantial threat to male reproductive health, while effective protective strategies remain limited. This study evaluated the protective effects of quercetin (Qu), a natural flavonoid, against T-2 toxin-induced testicular injury and investigated the underlying mechanisms, focusing on NLRP3 inflammasome-associated inflammation and fibrotic remodeling. Male ICR mice were exposed to T-2 toxin (1 mg/kg) for 28 days, with or without Qu (50 mg/kg) or the NLRP3 inhibitor MCC950 (20 mg/kg). Testicular morphology, TLR4/MyD88/NLRP3 pathway activation, pyroptosis-associated molecular changes, fibrotic remodeling, and blood-testis barrier (BTB)-associated proteins were assessed using histological staining, immunofluorescence, immunohistochemistry, and Western blotting. T-2 toxin exposure caused marked testicular histopathological alterations and activated the TLR4/MyD88/NLRP3 pathway, accompanied by increased IL-1β and IL-18 levels and alterations in pyroptosis-associated molecular markers in Leydig and Sertoli cells (P < 0.05). These changes were associated with increased TGF-β1 expression and peritubular collagen deposition, suggesting early fibrotic remodeling (P < 0.05). T-2 toxin also reduced the expression of the BTB-associated proteins ZO-1, occludin, CX43, claudin-1, and β-catenin (P < 0.05). Qu treatment attenuated testicular pathological changes and inflammasome-associated inflammatory responses, reduced early fibrotic remodeling, and restored BTB-associated protein expression. MCC950 intervention further supported the involvement of NLRP3 inflammasome-associated signaling in T-2 toxin-induced testicular injury. Collectively, these findings suggest that Qu alleviates T-2 toxin-induced testicular injury, at least in part, by modulating NLRP3 inflammasome-associated inflammation and fibrotic remodeling, thereby maintaining testicular homeostasis. Qu may therefore have potential for mitigating mycotoxin-induced reproductive toxicity. Nevertheless, because the conclusions regarding pyroptosis are based primarily on pathway-associated molecular markers in a murine model, further studies incorporating direct assessments of pyroptotic cell death and validation in higher-order animal models and clinical settings are warranted.
Xinzi Guo, Mingfa Yang, Yisheng Wang et al.· Toxicon· 0 citations
Cardiovascular diseases are increasingly linked to environmental toxicants, including widely used organophosphate pesticides. This study investigates the cardiotoxic potential of chlorpyrifos (CPF) and dimethoate (DM) using complementary in vivo and in vitro models. Female Wistar rats were orally exposed to CPF, DM and their combination for 30 days. Histopathological analyses revealed myocardial disarray, interstitial edema, inflammatory infiltration and aortic endothelial disruption, with combination group showing the most severe injury. Haematological alterations including reduced RBC and haemoglobin, elevated leukocyte and platelet counts were accompanied by significantly increased hydroxyproline content in heart and aorta, indicating early fibrotic remodelling. Molecular analysis demonstrated marked upregulation of NF-κB, NLRP3, IL-1β, IL-18 and TNF-α, along with suppression of eNOS, confirming activation of NF-κB/NLRP3 inflammasome axis and endothelial dysfunction. In vitro, CPF but not DM reduced endothelial cell viability and induced ROS generation and lactate dehydrogenase (LDH) release in HUVECs. CPF also elevated inflammatory and cell adhesion markers while downregulating eNOS and tight-junction proteins. Notably, NLRP3 inhibition by MCC950 mitigated CPF-induced inflammatory signaling and restored endothelial function. Collectively, these findings demonstrate that CPF and DM exposure induces cardiovascular injury mediated through oxidative stress, inflammasome activation and nitric oxide dysregulation, highlighting NLRP3 as a potential therapeutic target in pesticide-associated vascular toxicity.
Jasmeena Jan, Salman Shamas, Wajid Mohammad Sheikh et al.· Journal of Applied Toxicolog...· 0 citations
Results are best interpreted as gene‐level associations compatible with modulation of oxidative stress, inflammasome‐ and pyroptosis‐related mRNA expression, ER stress responses, apoptosis‐linked transcripts, and remodeling‐associated transcripts, rather than as confirmed pathway inhibition or established antifibrotic activity.
Aamir Sohail, Raza Sufyan, Muhammad Asim et al.· BioMed Research Internationa...· 0 citations
Aim: High-fructose corn syrup (HFCS) has been associated with metabolic and inflammatory disturbances, including pulmonary inflammatory injury. Due to its known anti-inflammatory and tissue-protective properties, this study aimed to investigate the protective effects of dexpanthenol (DEXP) against HFCS-induced structural and molecular lung damage in rat lungs.Material and Methods: Thirty-two male Wistar rats were allocated at random into four groups (Control, HFCS, HFCS+DEXP, DEXP). HFCS (30%) was provided in drinking water for 8 weeks. DEXP was administered intraperitoneally at a dose of 500 mg/kg/day for the last 2 weeks. Lung tissues were processed for hematoxylin–eosin and Picro Sirius Red staining. Hyperemia, edema, epithelial loss, inflammatory cell infiltration, and fibrosis were evaluated semi-quantitatively. The immunohistochemical expression of NF-κB and Caspase-3 was assessed as markers of inflammatory and apoptotic activities.Results: Exposure to HFCS produced alterations such as thickened alveolar walls, interstitial edema, vascular hyperemia, degeneration and loss of epithelial cells, accumulation of inflammatory cells, and early deposition of collagen compared with the control group. Histopathological scores for inflammation, edema, hyperemia, epithelial loss, and fibrosis were significantly increased in the HFCS group (p=0.001, p=0.001, p=0.001, p=0.006, and p=0.011, respectively). In addition, NF-κB and Caspase-3 expression levels were significantly elevated in the HFCS group compared with the control group (p=0.001). DEXP treatment significantly reduced histopathological scores (p=0.001), as well as NF-κB and Caspase-3 expression levels compared with the HFCS group (p=0.001 and p=0.0018, respectively). In the DEXP-only group, lung morphology was preserved.Conclusion: Chronic ingestion of HFCS elicits prominent inflammatory, apoptotic, and fibrotic responses in rat lung tissue. DEXP exerts strong histoprotective and immunomodulatory actions, suggesting potential therapeutic value against HFCS-induced pulmonary injury.
Şerife Taşan, Rahime Aslankoç, Cahide Aslan· Düzce Tıp Fakültesi Dergisi· 0 citations
It is suggested that DEX attenuates HFCS-induced liver injury through a multi-target mechanism involving suppression of oxidative damage, apoptosis, and inflammasome-associated pyroptotic signaling in young adult rats.
Abdulkerim Elmas, H. Aşçı, M. Y. Tepebaşı et al.· International Journal of Mol...· 0 citations