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

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 1, 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 kologram of body weight for 1, 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.