Glutathione depletion modulates methanol, formaldehyde and formate toxicity in cultured rat conceptuses

Cell Biology and Toxicology
C HarrisJason M Hansen

Abstract

The proposed use of methanol (H3COH) as an alternative to fossil fuels has prompted concern about potential health risks resulting from widespread environmental exposure. Methanol is teratogenic in rodents and, although the exact toxic species is not known, teratogenesis may result from the enzymatic biotransformation of H3COH to formaldehyde (CH2O) and formic acid causing increased biological reactivity and toxicity. A protective role for the antioxidant glutathione (GSH) has been described for H3COH, CH2O and formic acid toxicity in various biological systems but has yet to be evaluated in the developing conceptus. Whole embryo culture studies were conducted using GD 10-11 rat conceptuses to elucidate the relationship between H3COH and its metabolites and GSH status. Methanol exposure produced a decrease in normal growth parameters and a dose-dependent loss of viability. CH2O had deleterious effects on embryo growth and viability. Sodium formate (HCOONa) exposure resulted in a high mortality rate but viable embryos did not manifest any abnormalities. Methanol, CH2O, and HCOONa all produced a significant depletion of GSH in both embryo and VYS. Inhibition of GSH synthesis by L-buthionine-S,R-sulfoximine (BSO) treatment exacerb...Continue Reading

Citations

Feb 15, 2013·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·J R HutsonB M Kapur
Mar 6, 2012·Drug and Chemical Toxicology·M AbhilashR Harikumaran Nair
Jul 27, 2011·Mutation Research·Anh DuongLuoping Zhang
Oct 20, 2010·Reproductive Toxicology·J Nicole SweetingPeter G Wells
Jun 1, 2010·Toxicology and Applied Pharmacology·J Nicole SweetingPeter G Wells
Oct 8, 2013·Toxicology and Applied Pharmacology·Michelle T SiuPeter G Wells
Sep 25, 2012·Life Sciences·Veronica R MackeyClivel G Charlton
Dec 21, 2014·Biochimica Et Biophysica Acta·Jason M Hansen, Craig Harris
Mar 8, 2011·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·M AbhilashR Harikumaran Nair
Sep 30, 2006·Journal of Biochemical and Molecular Toxicology·Rajat Sandhir, Kamaljit Kaur
Apr 3, 2015·Physiological Reviews·Yuri L DorokhovTatiana V Komarova
Feb 23, 2007·Birth Defects Research. Part C, Embryo Today : Reviews·Jason M Hansen
Dec 4, 2004·Birth Defects Research. Part A, Clinical and Molecular Teratology·Jason M HansenCraig Harris

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