title: Improved Tissue-Based Analytical Test Methods for Orellanine, a Biomarker of Cortinarius Mushroom Intoxication.
abstract: Orellanine (OR) toxin is produced by mushrooms of the genus Cortinarius which grow in North America and in Europe. OR poisoning is characterized by severe oliguric acute renal failure, with a mortality rate of 10%-30%. Diagnosis of OR poisoning currently hinges on a history of ingestion of Cortinarius mushrooms and histopathology of renal biopsies. A key step in the diagnostic approach is analysis of tissues for OR. Currently, tissue-based analytical methods for OR are nonspecific and lack sensitivity. The objectives of this study were: (1) to develop definitive HPLC and LC-MS/MS tissue-based analytical methods for OR; and (2) to investigate toxicological effects of OR in mice. The HPLC limit of quantitation was 10 µg/g. For fortification levels of 15 µg/g to 50 µg/g OR in kidney, the relative standard deviation was between 1.3% and 9.8%, and accuracy was within 1.5% to 7.1%. A matrix-matched calibration curve was reproduced in this range with a correlation coefficient (r) of 0.97-0.99. The limit of detection was 20 ng/g for LC-MS/MS. In OR-injected mice, kidney OR concentrations were 97 ± 51 µg/g on Day 0 and 17 ± 1 µg/g on termination Day 3. Splenic and liver injuries were novel findings in this mouse model. The new tissue-based analytical tests will improve diagnosis of OR poisoning, while the mouse model has yielded new data advancing knowledge on OR-induced pathology. The new tissue-based analytical tests will improve diagnosis of OR poisoning, while the mouse model has yielded new data advancing knowledge on OR-induced pathology.
authors.affiliation: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. Poojyaa@iastate.edu.
authors.forename: Poojya
authors.initials: P
authors.lastname: Anantharam
authors.affiliation: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. shaodahai@gmail.com.
authors.forename: Dahai
authors.initials: D
authors.lastname: Shao
authors.affiliation: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. pmartin@iastate.edu.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Imerman
authors.affiliation: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. burrough@iastate.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Burrough
authors.affiliation: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. duey@iastate.edu.
authors.forename: Dwayne
authors.initials: D
authors.lastname: Schrunk
authors.affiliation: State Central Veterinary Laboratory, 8200 Zaisan, Khan-Uul District, Ulaanbaatar 017024, Mongolia. stsev@yahoo.com.
authors.forename: Tsevelmaa
authors.initials: T
authors.lastname: Sedkhuu
authors.affiliation: College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, China. tangshsh@cau.edu.cn.
authors.forename: Shusheng
authors.initials: S
authors.lastname: Tang
authors.affiliation: Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. rumbeiha@iastate.edu.
authors.forename: Wilson
authors.initials: W
authors.lastname: Rumbeiha
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D055363:Cortinarius; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009145:Mushroom Poisoning / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D009183:Mycotoxins / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D009183:Mycotoxins; C030076:orellanine; D015082:2,2'-Dipyridyl
keywords: Cortinarius mushrooms; HPLC; LC-MS/MS; analytical method; diagnosis; liver injury; orellanine; renal failure