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Toxicol Lett. 2019 May 15;306:61-65. doi: 10.1016/j.toxlet.2019.02.011. Epub 2019 Feb 16.

The relative toxicity of brodifacoum enantiomers.

Author information

1
Department of Anesthesiology, University of Illinois, Chicago, IL, 60612, USA; Jesse Brown VA Medical Center, Chicago, IL, 60612, USA. Electronic address: dlfeins@uic.edu.
2
Department of Anesthesiology, University of Illinois, Chicago, IL, 60612, USA. Electronic address: kgiersza@gmail.com.
3
Department of Pharmacology, University of Illinois, Chicago, IL, 60615, USA. Electronic address: aiqbal@uic.edu.
4
Department of Anesthesiology, University of Illinois, Chicago, IL, 60612, USA.
5
Department of Anesthesiology, University of Illinois, Chicago, IL, 60612, USA; Jesse Brown VA Medical Center, Chicago, IL, 60612, USA. Electronic address: richard.vanbreemen@oregonstate.edu.
6
Department of Pharmacology, University of Illinois, Chicago, IL, 60615, USA. Electronic address: mlindebl@uic.edu.
7
Department of Pharmacology, University of Illinois, Chicago, IL, 60615, USA. Electronic address: ad.zakharov16@gmail.com.
8
Department of Pharmacology, University of Illinois, Chicago, IL, 60615, USA. Electronic address: alyubimov1@gmail.com.
9
Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA.
10
Department of Anesthesiology, University of Illinois, Chicago, IL, 60612, USA; Jesse Brown VA Medical Center, Chicago, IL, 60612, USA. Electronic address: guyw@uic.edu.
11
Jesse Brown VA Medical Center, Chicago, IL, 60612, USA; Department of Medicine, University of Illinois, Chicago, IL, 60612, USA. Electronic address: irubinst@uic.edu.

Abstract

Brodifacoum (BDF) is a potent, long-acting anticoagulant rodenticide that can cause fatal poisoning in humans. The chemical structure of BDF includes 2 chiral carbons, resulting in 2 pairs of diastereomers, BDF-cis (R/S and S/R) and BDF-trans (R/R and S/S). However, the relative potency of these molecules is not known. The purpose of this study was to compare the in vitro and in vivo toxic effects of the 2 BDF diastereomer pairs. In adult Sprague-Dawley rats BDF-cis was significantly more toxic than BDF-trans (LD50 values of 219 versus 316 μg/kg, respectively) while racemic BDF had intermediate potency (266 μg/kg). In adult New Zealand white rabbits, BDF-cis had a longer half-life than BDF-trans which could contribute to its observed increased toxicity. Lastly, BDF-cis (10 μM), but not BDF-trans, damaged cultured SH-SY5Y human neuroblastoma cells by attenuating mitochondrial reductive capacity. Taken together, these data suggest that different toxic manifestations of BDF poisoning in mammals could be attributed, in part, to differences in relative enantiomer concentrations present in racemic formulations of this commercially-available toxicant.

KEYWORDS:

Anticoagulation; Brodifacoum; Diastereomer; Enantiomer; Superwarfarins

PMID:
30779948
PMCID:
PMC6408973
[Available on 2020-05-15]
DOI:
10.1016/j.toxlet.2019.02.011
[Indexed for MEDLINE]

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