Influence of Diisopropyl Fluorophosphate, an Irreversible Cholinesterase Inhibitor, on Metabolic and Inflammatory Parameters, Cardiac Function, Autonomic Modulation, and Angiotensin 1–7 Receptor

Nowadays, an estimate of 25–32% of approximately 700,000 Gulf War veterans affected by the Gulf War illness (GWI) still experience symptoms associated with their deployment. It is important to emphasize that GWI is an archetypal, medically unexplained, chronic condition. Musculoskeletal pain, cognitive dysfunction, unexplained fatigue, exercise intolerance, chronic diarrhea, rashes, sleep disorders, and respiratory problems are some of the symptoms observed in Gulf War veterans affected by GWI. Understanding the mechanisms involved in GWI is important to provide a better assistance/treatment to this population. In this study, we used mice to verify the influence of Diisopropyl fluorophosphate (DFP), an irreversible cholinesterase inhibitor used to mimic the effects of sarin gas used during the Gulf War, on metabolic and inflammatory parameters, cardiac function (ECHO), autonomic modulation (spectral analysis) and angiotensin 1–7 receptor (Radioligand Binding Assay) in liver. The animals exposed to DFP showed lower levels of glucose (−8%), triglycerides (−23%) and IL‐10 (−32%), lower parasympathetic modulation (−33%), which led to a higher sympathovagal balance. They showed a lower ejection fraction (−13%) and higher myocardial performance index (30%), characterizing a cardiac dysfunction. In addition, they showed higher Bmax for 125/127I‐Angiotensin 1–7 binding assay, which represents a higher number of receptors (28%). Our results show that exposure to DFP leads to alterations on metabolic and inflammatory parameters, cardiac function, autonomic modulation, and renin‐angiotensin‐aldosterone system, which helps us to understand, at least in part, the mechanisms involved in GWI. Further studies are needed to elucidate the whole mechanisms behind GWI.