Organophosphate Pesticides Promote Cardiovascular Toxicity via NF-κB/NLRP3 Inflammasome Activation and Endothelial...

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.