Abstract
Paraquat (PQ) poisoning has high mortality rates in many countries. Due to it readily being absorbed through the gastrointestinal tract and rapidly excreted in the urine, few biomarkers possess satisfactory specificity and sensitivity in diagnostic and forensic practices. To investigate serum biomarkers in patients with PQ poisoning, pooled sera was analyzed using a proteomic approach based on iTRAQ coupled LC-MS/MS. Of the 413 proteins identified with high confidence, 81 were found to be differentially expressed (1.5-fold change) in the sera of patients with PQ poisoning. The differential expression pattern of 4 of these proteins was validated by enzyme-linked immunosorbent assay (ELISA) in clinical samples. A sera sample from a PQ poisoning patient has shown relatively increased abundance of S100A8 and S100A9. The overexpression of S100A8 and S100A9 was further validated in the lung tissue of PQ-treated rat associated with lung damage. Meanwhile, we identified another two down-expressed proteins, transferrin receptor protein 1 (TfR1) and serum amyloid P-component (SAP), which may be also practicable in human clinical samples as PQ poisoning serum biomarkers. Furthermore, receiver operating characteristic curve analysis confirmed that the expression levels of S100 alarmins, TfR1 and SAP in patient serum could provide a discriminatory diagnostic test for predicting PQ poisoning in patients. Therefore, our results suggest that increased serum levels of S100 alarmins and decreased serum levels of TfR1 and SAP may constitute potential biomarkers for the prediction of PQ poisoning in humans, and might be novel therapeutic targets in PQ poisoning.
Highlights
Paraquat dichloride (1,10-dimethyl-4,40-bipyridinium dichloride methyl viologen, PQ) is one of the most widely used herbicides in the world and can be lethal when ingested by humans.[1,2] With the widespread use of this herbicide in many countries, the incidence of PQ poisoning has trended upward over the last several decades due to accidental and intentional ingestion of the product
To gain insight into the biological functions of the proteins exhibiting altered expression in the patients with PQ poisoning, the differentially expressed proteins were categorized according to their annotation in the Gene Ontology (GO) database
This study demonstrated that S100A8 and S100A9 are overexpressed in the sera of PQ poisoning human patients and PQ-treated rat
Summary
Paraquat dichloride (1,10-dimethyl-4,40-bipyridinium dichloride methyl viologen, PQ) is one of the most widely used herbicides in the world and can be lethal when ingested by humans.[1,2] With the widespread use of this herbicide in many countries, the incidence of PQ poisoning has trended upward over the last several decades due to accidental and intentional ingestion of the product. PQ is absorbed into the bloodstream through the gastrointestinal tract, the lungs are the primary site of PQ-induced injury in humans and animals. PQ is readily absorbed through the gastrointestinal tract and rapidly excreted in the urine.[6,7] Prediction of survival in patients with PQ intoxication is closely related to the amount of PQ ingested, as well as the amount of time that passes between exposure and treatment. There is a lack of effective diagnostic methods for PQ intoxication due to considerable clearance of the compound from the blood within hours following exposure. Several novel methods and indicators have been reported to evaluate the diagnosis of PQ intoxication, which including arterial blood gas analysis,[8] serum creatinine or cystatin C A major limitation of these indicators is the unreliability and instability
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