PMID- 24095963
OWN - NLM
STAT- MEDLINE
DCOM- 20140210
LR  - 20191210
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 273
IP  - 3
DP  - 2013 Dec 15
TI  - A role for glutathione, independent of oxidative stress, in the developmental 
      toxicity of methanol.
PG  - 508-15
LID - S0041-008X(13)00420-1 [pii]
LID - 10.1016/j.taap.2013.09.020 [doi]
AB  - Oxidative stress and reactive oxygen species (ROS) have been implicated in the 
      teratogenicity of methanol (MeOH) in rodents, both in vivo and in embryo culture. 
      We explored the ROS hypothesis further in vivo in pregnant C57BL/6J mice. 
      Following maternal treatment with a teratogenic dose of MeOH, 4 g/kg via 
      intraperitoneal (ip) injection on gestational day (GD) 12, there was no increase 
      6h later in embryonic ROS formation, measured by 2',7'-dichlorodihydrofluorescin 
      diacetate (DCFH-DA) fluorescence, despite an increase observed with the positive 
      control ethanol (EtOH), nor was there an increase in embryonic oxidatively 
      damaged DNA, quantified as 8-oxo-2'-deoxyguanosine (8-oxodG) formation. MeOH 
      teratogenicity (primarily ophthalmic anomalies, cleft palate) also was not 
      altered by pre- and post-treatment with varying doses of the free radical spin 
      trapping agent alpha-phenyl-N-tert-butylnitrone (PBN). In contrast, pretreatment 
      with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione (GSH) 
      synthesis, depleted maternal hepatic and embryonic GSH, and enhanced some new 
      anomalies (micrognathia, agnathia, short snout, fused digits, cleft lip, low set 
      ears), but not the most common teratogenic effects of MeOH (ophthalmic anomalies, 
      cleft palate) in this strain. These results suggest that ROS did not contribute 
      to the teratogenic effects of MeOH in this in vivo mouse model, in contrast to 
      results in embryo culture from our laboratory, and that the protective effect of 
      GSH in this model may arise from its role as a cofactor for formaldehyde 
      dehydrogenase in the detoxification of formaldehyde.
CI  - (c) 2013.
FAU - Siu, Michelle T
AU  - Siu MT
AD  - Division of Biomolecular Sciences, Faculty of Pharmacy, University of Toronto, 
      Toronto, Ontario, Canada.
FAU - Shapiro, Aaron M
AU  - Shapiro AM
FAU - Wiley, Michael J
AU  - Wiley MJ
FAU - Wells, Peter G
AU  - Wells PG
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131002
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Cyclic N-Oxides)
RN  - 0 (Free Radicals)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Teratogens)
RN  - 131202-22-7 (buthionine sulfoximine ethyl ester)
RN  - 1982-67-8 (Methionine Sulfoximine)
RN  - 3I91332OPG (phenyl-N-tert-butylnitrone)
RN  - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine)
RN  - EC 1.2.- (Aldehyde Oxidoreductases)
RN  - EC 1.2.1.46 (formaldehyde dehydrogenase, glutathione-independent)
RN  - G9481N71RO (Deoxyguanosine)
RN  - GAN16C9B8O (Glutathione)
RN  - Y4S76JWI15 (Methanol)
SB  - IM
MH  - 8-Hydroxy-2'-Deoxyguanosine
MH  - Aldehyde Oxidoreductases/pharmacology
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - Cyclic N-Oxides/pharmacology
MH  - DNA Damage/drug effects
MH  - Deoxyguanosine/analogs & derivatives/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Embryo, Mammalian/drug effects/metabolism
MH  - Female
MH  - Free Radicals/metabolism
MH  - Glutathione/*pharmacology
MH  - Male
MH  - Methanol/*toxicity
MH  - Methionine Sulfoximine/analogs & derivatives/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidative Stress/*drug effects
MH  - Pregnancy
MH  - Reactive Oxygen Species/metabolism
MH  - Tandem Mass Spectrometry
MH  - Teratogens/toxicity
OTO - NOTNLM
OT  - 2',7'-dichlorodihydrofluorescin diacetate
OT  - 5,5'-dithiobis-(2-nitrobenzoic acid)
OT  - 8-oxo-2'-deoxyguanosine
OT  - 8-oxodG
OT  - ADH1
OT  - ADH3
OT  - BSO
OT  - DCFH-DA
OT  - DMSO
OT  - DTNB
OT  - EtOH
OT  - FA
OT  - Formaldehyde
OT  - GD
OT  - GSH
OT  - GSSG
OT  - Glutathione
OT  - H(2)O(2)
OT  - HNE
OT  - HPLC
OT  - LC-MS/MS
OT  - MeOH
OT  - Methanol
OT  - NADPH oxidase
OT  - NF-kappaB
OT  - NOX
OT  - NTD
OT  - NZW
OT  - Na-FA
OT  - New Zealand White rabbits
OT  - Oxidative stress
OT  - PBN
OT  - RFU
OT  - ROS
OT  - Reactive oxygen species
OT  - Teratogenesis
OT  - alcohol dehydrogenase
OT  - alpha-phenyl-N-tert-butylnitrone
OT  - dimethyl sulfoxide
OT  - ethanol
OT  - formaldehyde dehydrogenase
OT  - formic acid
OT  - gestational day
OT  - high-performance liquid chromatography
OT  - hydrogen peroxide
OT  - hydroxynonenal
OT  - intraperitoneal
OT  - ip
OT  - l-buthionine-(S,R)-sulfoximine
OT  - liquid chromatography with tandem mass spectrometry
OT  - methanol
OT  - neural tube defect
OT  - nuclear factor transcription factor kappa-B
OT  - oxidized glutathione
OT  - reactive oxygen species
OT  - reduced glutathione
OT  - relative fluorescence units
OT  - sodium formate
EDAT- 2013/10/08 06:00
MHDA- 2014/02/11 06:00
CRDT- 2013/10/08 06:00
PHST- 2013/05/03 00:00 [received]
PHST- 2013/09/06 00:00 [revised]
PHST- 2013/09/23 00:00 [accepted]
PHST- 2013/10/08 06:00 [entrez]
PHST- 2013/10/08 06:00 [pubmed]
PHST- 2014/02/11 06:00 [medline]
AID - S0041-008X(13)00420-1 [pii]
AID - 10.1016/j.taap.2013.09.020 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2013 Dec 15;273(3):508-15. doi: 
      10.1016/j.taap.2013.09.020. Epub 2013 Oct 2.