The effect of L-dopa administration and folate deficiency on plasma homocysteine concentrations in rats

Deborah Daly, Joshua W. Miller, Marie R. Nadeau, Jacob Selhub

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

O-Methylation of the anti-Parkinson's disease drug L-dopa leads to significant decreases of S-adenosylmethionine and significant increases of S-adenosylhomocysteine concentrations in tissues. Based on these observations, we hypothesized that L-dopa administration would also lead to increased production of homocysteine and hyperhomocysteinemia. This hypothesis was tested in two separate experiments. In experiment I, control and folate-deficient male rats were injected intraperitoneally with 100 mg of L-dopa per kilogram body weight. After 1 hr, blood was collected and analyzed for homocysteine. Plasma homocysteine concentration was significantly higher in the rats treated with L-dopa than in the rats treated with vehicle alone. Furthermore, the apparent increase of plasma homocysteine due to L-dopa was greater in the folate-deficient rats than in the replete controls, suggesting a significant interaction between L-dopa administration and folate deficiency on plasma homocysteine concentration. In experiment 2, nondeficient female rats were injected intraperitoneally with 100 mg of L-dopa per kilogram of body weight for 0, 1, or 17 consecutive days (one injection per day). Blood was collected 1 hr after the last dose and analyzed for homocysteine. Plasma homocysteine: concentration was significantly higher In-the rats treated for 17 days than in the nontreated controls, indicating that the effect of L-dopa persisted with chronic administration. However, plasma homocysteine concentration was significantly higher in the rats treated with L-dopa for only 1 day than in those treated for 17 days, suggesting that there is some attenuation of the effect of L-dopa with chronic administration. Measurements of S-adenosylmethionine and S-adenosylhomocysteine in brain and liver were consistent with the hypothesis that the hyperhomocysteinemia was a consequence of significant O-methylation.

Original languageEnglish (US)
Pages (from-to)634-640
Number of pages7
JournalJournal of Nutritional Biochemistry
Volume8
Issue number11
DOIs
StatePublished - Nov 1997
Externally publishedYes

Keywords

  • Folate
  • L-homocysteine
  • S-adenosylhomocysteine
  • S-adenosylmethionine

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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