LC-MS/MS-Profiling of Human Serum Unveils Significant Increase in Neuroinflammation and Carcinogenesis Following Chronic Organophosphate Exposure

Abstract

The utilization of organophosphate pesticides (OPs) has escalated in response to the growing global food demand driven by a rapidly increasing population and the environmental disruptions caused by climate change. While acute exposure leads to cholinergic poisoning, chronic OP exposure has been linked to organ dysfunction, inflammation, and carcinogenesis. Serum samples from healthy individuals (<i>n</i> = 11), patients with acute OP exposure (<i>n</i> = 12), and those with chronic OP exposure (<i>n</i> = 31) were analyzed to discern the differentially expressed pathways after acute and chronic OP exposure. Differential expression analysis identified 132 proteins altered in chronic exposure vs control, 86 in acute exposure vs control, and 124 in chronic vs acute exposure. Pathway analysis revealed increased blood coagulation and reduced LXR/RXR activation and DCHR24 signaling in both acute and chronic exposures. Elevated levels of pro-inflammatory proteins, such as S100A8, VWF, and GPIBA, were observed, particularly in chronic exposure, highlighting significant inflammatory effects of OP exposure. These findings provide insights into the pathological mechanisms underlying chronic OP exposure and its contribution to inflammation and long-term health risks.