Chronic Exposure to Organophosphate Pesticides and Elevated Markers of Systemic Inflammation: Possible Neuroinflammatory and Genotoxic Effects

Abstract

<b>Abstract ID 19069</b> <b>Poster Board 27</b> <b>Introduction:</b> Climate change alters not only cultivation seasons but also pest population. This led to adaptive responses in the farming industry increasing organophosphate pesticide (OP) use. This is particularly problematic in smallholder growers self-applying pesticides without the appropriate safety precautions. Several studies addressed the neurotoxic and metabolic effects of chronic exposure to OPs including delayed polyneuropathy and Gulf War Illness. Further, some studies highlighted a controversial link between chronic organophosphate exposure and the development of neurodegenerative diseases. While these neurotoxic effects were attributed to various mechanisms besides neurotoxic esterase inhibition, including inflammation, systematic examination of the inflammatory and cell damage consequences have not been forthcoming. <b>Aim:</b> To conduct targeted, proteomic and glycomic examination of markers of inflammation, nerve damage, and metabolic dysfunction in serum samples of smallholder vegetable farmers with repeated exposure to selected Ops, as well as assessing the different potential cytotoxic effects of these OPs. <b>Methodology:</b> Serum samples (n=31) were obtained from male farmers (18-60 years old) with chronic OP exposure, after signing an informed consent. A questionnaire was used to collect patients’ demographics, years of OPs exposure, as well as their general health status, history of the types of pesticides contacted, and development of cholinergic symptoms, if any. Serum markers measured include: Interleukin 6 (IL-6) &amp; C-Reactive protein (CRP), full lipid panel, liver enzymes (ALT &amp; AST), and serum creatinine (sCr). These parameters were compared to values in a corresponding control group of healthy city dwellers with matched age and gender. Alongside, a fluorimetric DNA probe assay was used to determine the DNA damage kinetics induced by profenophos and chlorpyrifos, commonly used OPs. Student’s <i>t</i>-test was used to compare the parameters measured. A <i>P</i>-value &lt; 0.05 was considered significant. <b>Results</b>: Compared to healthy controls, subjects with repeated exposure to OPs showed an elevation of liver (AST: 30.86±1.89 vs. 18.88±1.04 U/L in control) and kidney function parameters (sCr: 1.1±0.03 vs. 0.88±0.05 mg/dl in control), as well as IL-6 (5.17±0.2 vs. 3.19±0.4 pg/ml in control), indicating a subtle state of liver and renal impairment as well as chronic inflammation. No changes in serum CRP or lipids were observed. Interestingly, none of the elevated markers correlated positively with the self-reported severity of cholinergic symptoms occurring immediately after exposure, potentially precluding cholinesterase inhibition as the cause for the observed impairment. On the other hand, profenofos and chlorpyrifos were shown to induce significant DNA damage, with double strand breaks observed with concentrations as low as 200 and 400 nmol/L, respectively. <b>Conclusions:</b> Chronic exposure to OPs appears to induce inflammation and organ impairment that are not related to cholinesterase inhibition. Potential mechanisms include possible cytotoxic effects through DNA damage. Further studies are underway to assess the apoptotic potential of OPs and to profile their proteomic and glycomic impact on subjects of chronic exposure.