THE EFFECT OF L-DOPA ADMINISTRATION AND FOLATE-DEFICIENCY ON PLASMA HOMOCYSTEINE CONCENTRATIONS IS RATS

O-Methylation of the anti-Parkinson's disease drug L-dopa leads to sig nificant decreases of S-adenosylmethionine and significant increases o f S-adenosylhomocysteine concentrations in tissues. Based on these obs ervations, 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 1, c ontrol 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 concentra tion was significantly higher in the rats treated with L-dopa than in the rats treated with vehicle alone. Furthermore, the apparent increas e of plasma homocysteine due to L-dopa was greater in the folate-defic ient rats than in the replete controls, suggesting a significant inter action between L-dopa administration and folate deficiency on plasma h omocysteine concentration. In experiment 2, nondeficient female rats w ere injected intraperitoneally with 100 mg of L-dopa per kilogram of b ody weight for 0, 1, or 17 consecutive days (one injection per day). B lood was collected 1 hr after the last dose and analyzed for homocyste ine. 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. Howev er, plasma homocysteine concentration was significantly higher in the rats treated with L-dopa for only 1 day than in those treated for 17 d ays, 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 hy pothesis that the hyperhomocysteinemia was a consequence of significan t O-methylation. (C) Elsevier Science Inc, 1997.