PMID- 30090460
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240329
IS  - 2045-452X (Print)
IS  - 2045-4538 (Electronic)
IS  - 2045-452X (Linking)
VI  - 5
IP  - 6
DP  - 2016 Nov 1
TI  - Global metabolic changes induced by plant-derived pyrrolizidine alkaloids 
      following a human poisoning outbreak and in a mouse model.
PG  - 1594-1603
LID - 10.1039/c6tx00221h [doi]
AB  - Several hundred cases of Hirmi Valley Liver Disease (HVLD), an often fatal liver 
      injury, occurred from 2001 to 2011 in a cluster of rural villages in Tigray, 
      Ethiopia. HVLD is principally caused by contamination of the food supply with 
      plant derived pyrrolizidine alkaloids (PAs), with high exposure to the pesticide 
      DDT among villagers increasing their susceptibility. In an untargeted global 
      approach we aimed to identify metabolic changes induced by PA exposure through 
      (1)H NMR spectroscopic based metabolic profiling. We analysed spectra acquired 
      from urine collected from HVLD cases and controls and a murine model of PA 
      exposure and PA/DDT co-exposure, using multivariate partial least squares 
      discriminant analysis. In the human models we identified changes in urinary 
      concentrations of tyrosine, pyruvate, bile acids, N-acetylglycoproteins, 
      N-methylnicotinamide and formate, hippurate, p-cresol sulphate, p-hydroxybenzoate 
      and 3-(3-hydroxyphenyl) propionic acid. Tyrosine and p-cresol sulphate were 
      associated with both exposure and disease. Similar changes to tyrosine, 
      one-carbon intermediates and microbial associated metabolites were observed in 
      the mouse model, with tyrosine correlated with the extent of liver damage. These 
      results provide mechanistic insight and implicate the gut microflora in the human 
      response to challenge with toxins. Pathways identified here may be useful in 
      translational research and as "exposome" signals.
FAU - Robinson, Oliver
AU  - Robinson O
AD  - MRC-PHE Centre for Environment and Health , School of Public Health , Imperial 
      College London , UK.
AD  - ISGlobal , Centre for Research in Environmental Epidemiology (CREAL) , Spain.
AD  - Hospital del Mar Medical Research Institute (IMIM) , Barcelona , Spain.
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP) , Spain.
FAU - Toledano, Mireille B
AU  - Toledano MB
AD  - MRC-PHE Centre for Environment and Health , School of Public Health , Imperial 
      College London , UK.
FAU - Sands, Caroline
AU  - Sands C
AD  - Computational and Systems Medicine , Department of Surgery & Cancer , Faculty of 
      Medicine , Imperial College London , UK . Email: m.coen@imperial.ac.uk.
FAU - Beckonert, Olaf
AU  - Beckonert O
AD  - Computational and Systems Medicine , Department of Surgery & Cancer , Faculty of 
      Medicine , Imperial College London , UK . Email: m.coen@imperial.ac.uk.
FAU - J Want, Elizabeth
AU  - J Want E
AD  - Computational and Systems Medicine , Department of Surgery & Cancer , Faculty of 
      Medicine , Imperial College London , UK . Email: m.coen@imperial.ac.uk.
FAU - Goldin, Rob
AU  - Goldin R
AD  - Department of Medicine , Imperial College London , UK.
FAU - Hauser, Michael L
AU  - Hauser ML
AD  - One Health Foundation , Switzerland.
AD  - Schistosomiasis Control Initiative , School of Public Health, Imperial College , 
      London , UK.
FAU - Fenwick, Alan
AU  - Fenwick A
AD  - Schistosomiasis Control Initiative , School of Public Health, Imperial College , 
      London , UK.
FAU - Thursz, Mark R
AU  - Thursz MR
AD  - Department of Medicine , Imperial College London , UK.
FAU - Coen, Muireann
AU  - Coen M
AD  - Computational and Systems Medicine , Department of Surgery & Cancer , Faculty of 
      Medicine , Imperial College London , UK . Email: m.coen@imperial.ac.uk.
LA  - eng
GR  - G0701716/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20160812
PL  - England
TA  - Toxicol Res (Camb)
JT  - Toxicology research
JID - 101587950
PMC - PMC6060677
MID - EMS78763
EDAT- 2016/08/12 00:00
MHDA- 2016/08/12 00:01
PMCR- 2017/08/12
CRDT- 2018/08/10 06:00
PHST- 2016/05/21 00:00 [received]
PHST- 2016/08/11 00:00 [accepted]
PHST- 2018/08/10 06:00 [entrez]
PHST- 2016/08/12 00:00 [pubmed]
PHST- 2016/08/12 00:01 [medline]
PHST- 2017/08/12 00:00 [pmc-release]
AID - c6tx00221h [pii]
AID - 10.1039/c6tx00221h [doi]
PST - epublish
SO  - Toxicol Res (Camb). 2016 Aug 12;5(6):1594-1603. doi: 10.1039/c6tx00221h. 
      eCollection 2016 Nov 1.