title: Detection of Carbofuran-Protein Adducts in Serum of Occupationally Exposed Pesticide Factory Workers in Pakistan.
abstract: This study was conducted to investigate the protein adducts with pesticides in a cohort of 172 factory workers that were exposed to a mixture of pesticides. The 35 samples showing considerable variation in biochemical parameters, i.e., butyrylcholinestrase (BChE), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), gamma-glutamyl transferase (GGT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP/ALKP), lactate dehydrogenase (LDH), creatine phosphokinase (CPK) enzymes, and controls were analyzed by reversed-phase nanoscale liquid chromatography tandem mass spectrometry (nLC-MS/MS) on an Orbitrap mass spectrometer employing a shotgun proteomics approach. Only protein adducts with carbofuran were found on serum proteins of these workers. These adducts were of carbofuran labeled lysine (Lys-142, Lys-183, Lys-287, and Lys-467), arginine (Arg-210, Arg-242, and Arg-256) from serum albumin, and serine (Ser-07, Ser-54, and Ser-150) from immunoglobulin proteins. The arginine residues (Arg-210, Arg-242, Arg-246, and Arg-434) from albumin were also found to be glycated in serum of workers showing a high level of glucose who also had glycated arginine (Arg-1120) modified with carbofuran in their tankyrase-1-binding protein. The number of tandem mass spectra of modified peptides increased with increasing time of exposure. This is the first report to demonstrate the presence of carbofuran-labeled albumin, immunoglobulin, and glycated arginine, which shows that lysine and arginine of human albumin and serine of immunoglobulin are covalently modified in the serum of workers that were occupationally exposed to carbofuran, and the modification is detectable by tandem mass spectrometry. These peptides modified with carbofuran can potentially be used as a biomarker of carbofuran exposure.
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy , Baltimore, Maryland 21201, United States.
authors.forename: Tanzila
authors.initials: T
authors.lastname: Rehman
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy , Baltimore, Maryland 21201, United States.
authors.forename: Mohd M
authors.initials: MM
authors.lastname: Khan
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Shad
authors.forename: Mazhar
authors.initials: M
authors.lastname: Hussain
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy , Baltimore, Maryland 21201, United States.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Oyler
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy , Baltimore, Maryland 21201, United States.
authors.forename: Young Ah
authors.initials: YA
authors.lastname: Goo
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy , Baltimore, Maryland 21201, United States.
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett