title: Use of a glyphosate-based herbicide-induced nephrotoxicity model to investigate a panel of kidney injury biomarkers.
abstract: Accidental or intentional ingestion of glyphosate surfactant-based herbicides, like Roundup(®), leads to nephrotoxicity as well as death. In this study, a panel of kidney injury biomarkers was evaluated in terms of suitability to detect acute kidney injury and dysfunction. The Roundup(®) intoxication model involved oral administration of glyphosate to rats at dose levels of 250, 500, 1200 and 2500 mg/kg. Urinary and plasma biomarker patterns were investigated at 8, 24 and 48 h after dosing. Biomarkers were quantified by absolute concentration; by normalising to urine creatinine; and by calculating the excretion rate. The diagnostic performances of each method in predicting of acute kidney injury were compared. By Receiver Operating Characteristic (ROC) analysis of the selected biomarkers, only urinary kidney injury molecule-1 (KIM-1) best predicted histological changes at 8h (best cut-off point>0.00029 μg/ml). Plasma creatinine performed better than other biomarkers at 24 h (best cut-off point>0.21 mg/dl). Urinary KIM-1 was the best early biomarker of kidney injury in this glyphosate-induced nephrotoxicity model.
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Brisbane, QLD, Australia; Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Klintean
authors.initials: K
authors.lastname: Wunnapuk
authors.affiliation: Centre for Kidney Disease Research, School of Medicine, The University of Queensland, Brisbane, Australia.
authors.forename: Glenda
authors.initials: G
authors.lastname: Gobe
authors.affiliation: Centre for Kidney Disease Research, School of Medicine, The University of Queensland, Brisbane, Australia; Department of Nephrology, Prince of Wales Clinical School and Prince of Wales Hospital, Randwick, NSW, Australia.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Endre
authors.affiliation: Department of Nephrology, Prince of Wales Clinical School and Prince of Wales Hospital, Randwick, NSW, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Peake
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Grice
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Brisbane, QLD, Australia; School of Pharmacy & Medical Sciences, University of South Australia, Adelaide, SA, Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
authors.affiliation: South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Sri Lanka; Professorial Medicine Unit, University of New South Wales, NSW, Australia.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Buckley
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Brisbane, QLD, Australia. Electronic address: xin.liu@uq.edu.au.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D000209:Acute-Phase Proteins; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015815:Cell Adhesion Molecules / Q000652:urine*; D016923:Cell Death / Q000187:drug effects; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C / Q000097:blood; D042241:Early Diagnosis; D005998:Glycine / Q000031:analogs & derivatives* / Q000633:toxicity; D006540:Herbicides / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood; D008297:Male; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000097:blood; D012372:ROC Curve; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000652:urine; D000097797:Glyphosate
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D003404:Creatinine; D055316:Cystatin C; D005998:Glycine; D006540:Herbicides; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D000097797:Glyphosate; C110936:Havcr1 protein, rat; C097278:Lcn2 protein, rat; C467498:vascular endothelial growth factor A, rat
keywords: Acute kidney injury; Creatinine; Cystatin-C; Glyphosate; Kidney injury molecule-1; Roundup