Alcohol abuse during pregnancy has been associated with Fetal Alcohol Spectrum Disorder (FASD). Research to date has focused on the role played by ethanol in the development of this disorder. In addition to ethanol, alcoholic drinks also contain methanol. Hence, consumption of alcohol can also lead to methanol accumulation. Methanol is metabolized to formaldehyde, which is then rapidly metabolized to formate, a toxic metabolite. Folate, a B-vitamin and antoxidant, is a cofactor in the metabolism of formate. This study assessed the relationship between formate and folate, formate kinetics in folate deficiency and, changes in antioxidant capacity during formate insult in folate deficiency. The findings of this study would lead to a better understanding of the role of formate in the development of the etiology of FASD and form the basis of future research.
The relationship between formate and folate was investigated in intoxicated human female subjects, sober drug rehabilitating females and, pregnant women. A negative (inverse) relationship was observed between plasma formate and folate in pregnant sober women (correlation coefficient = -0.4989). Such a relationship, however, was not observed in whole blood in alcohol intoxicated (correlation coefficient = 0.0899) and detox women (correlation coefficient = 0.2382). Because of the health promoting ingredients in grain and fruit based alcoholic drinks, antioxidant B-vitamins were higher during intoxication while homocysteine levels were lower.<p>Formate kinetics during folate deficiency and changes in the body antioxidant capacity was investigated in folate deficient young swine. Folate deficiency altered formate kinetics leading to decreased systemic clearance (by approximately 2.3 fold), increased half-life (by 2.5 fold) and, consequently increased exposure (by 2.7 fold). Folate deficiency alone compromised antioxidant capacity. However, the combination of folate deficiency and formate insult further compromised antioxidant capacity.<p>In conclusion, methanol accumulates after alcohol intoxication, which can lead to formate build up in the body. During folate deficiency formate kinetics is altered leading to reduced formate clearance and increased exposure. Exposure to formate coupled to folate deficiency compromises antioxidant capacity, which can have deleterious effects on the fetus.
| Identifer | oai:union.ndltd.org:USASK/oai:usask.ca:etd-08212007-103509 |
| Date | 22 August 2007 |
| Creators | Sokoro, AbdulRazaq Abubakar Hamud |
| Contributors | Lehotay, Denis C. |
| Publisher | University of Saskatchewan |
| Source Sets | University of Saskatchewan Library |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-08212007-103509/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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