Glutathione depletion modulates methanol, formaldehyde and formate toxicity in cultured rat conceptuses
dc.contributor.author | Harris, C. | en_US |
dc.contributor.author | Dixon, M. | en_US |
dc.contributor.author | Hansen, Jason M. | en_US |
dc.date.accessioned | 2006-09-08T20:27:51Z | |
dc.date.available | 2006-09-08T20:27:51Z | |
dc.date.issued | 2004-05 | en_US |
dc.identifier.citation | Harris, C.; Dixon, M.; Hansen, J.M.; (2004). "Glutathione depletion modulates methanol, formaldehyde and formate toxicity in cultured rat conceptuses." Cell Biology and Toxicology 20(3): 133-145. <http://hdl.handle.net/2027.42/42552> | en_US |
dc.identifier.issn | 0742-2091 | en_US |
dc.identifier.issn | 1573-6822 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/42552 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=15250539&dopt=citation | en_US |
dc.description.abstract | The proposed use of methanol (H 3 COH) 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 H 3 COH to formaldehyde (CH 2 O) and formic acid causing increased biological reactivity and toxicity. A protective role for the antioxidant glutathione (GSH) has been described for H 3 COH, CH 2 O 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 H 3 COH and its metabolites and GSH status. Methanol exposure produced a decrease in normal growth parameters and a dose-dependent loss of viability. CH 2 O 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, CH 2 O, 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 exacerbated H 3 COH, CH 2 O and HCOONa embryotoxicity. Interestingly, only H 3 COH/BSO and CH 2 O/BSO co-treatments caused increased malformation, while embryos treated with HCOONa/BSO did not produce any developmental deformities. These results implicate CH 2 O as the most embryotoxic H 3 COH metabolite, on a molar basis, in terms of causing dysmorphogenesis, alterations of normal growth parameters and embryolethality. HCOONa was selectively embryolethal and did not produce dysmorphogenesis. CH 2 O toxicity is potentiated by GSH depletion, indicating that GSH may be more directly involved in its detoxication in the embryo. | en_US |
dc.format.extent | 258891 bytes | |
dc.format.extent | 3115 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Kluwer Academic Publishers; Springer Science+Business Media | en_US |
dc.subject.other | Life Sciences | en_US |
dc.subject.other | Pharmacology/Toxicology | en_US |
dc.subject.other | Biochemistry, General | en_US |
dc.subject.other | Cell Biology | en_US |
dc.subject.other | Embryo | en_US |
dc.subject.other | Formaldehyde | en_US |
dc.subject.other | Formic Acid | en_US |
dc.subject.other | Glutathione | en_US |
dc.subject.other | Methanol | en_US |
dc.subject.other | Visceral Yolk Sac | en_US |
dc.title | Glutathione depletion modulates methanol, formaldehyde and formate toxicity in cultured rat conceptuses | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Public Health | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Toxicology Program, Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationum | Toxicology Program, Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA | en_US |
dc.contributor.affiliationother | Department of Biochemistry, Emory University, Atlanta, Georgia, USA | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 15250539 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/42552/1/10565_2004_Article_5275345.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1023/B:CBTO.0000029466.08607.86 | en_US |
dc.identifier.source | Cell Biology and Toxicology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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