In-vitro interaction of l-dopa with bacterial adhesins of Helicobacter pylori: an explanation for clinicial differences in bioavailability?

Abstract

Abstract Objectives Recent investigations on the pharmacokinetics of levodopa (l-dopa) indicated that the presence of Helicobacter pylori in patients with Parkinson's disease, orally treated with l-dopa, influences the absorption of this compound, which consequently leads to decreased plasma levels. Therefore this work aims to study a potential in-vitro interaction of l-dopa with H. pylori and its surface adhesins. Methods Solutions containing l-dopa of different concentrations were incubated with H. pylori at different bacterial densities and time intervals. Free l-dopa was quantified from the incubation supernatants by HPLC. A flow cytometric assay with fluorescence labelled H. pylori was used to investigate the influence of l-dopa on the bacterial adhesion of H. pylori: FITC-labelled bacteria were pre-incubated with l-dopa, followed by incubation with gastric epithelial cells (AGS cells) and FACS quantification of adhering bacteria. Key findings Evaluation of time- and concentration-dependent incubation experiments indicated a significant decrease in l-dopa concentrations when coming into contact with H. pylori. The reduction in l-dopa concentrations was determined as 47 to 12%, referred to the initial starting concentration, with time-dependency and dependency of the H. pylori density. FITC-labelled H. pylori, pre-incubated with differing l-dopa concentrations, were shown to have a significantly reduced bacterial adhesion to AGS cells, with a maximum reduction of 22 ± 9%. These results demonstrate a direct interaction of l-dopa with the outer membrane proteins of H. pylori responsible for the adhesion to gastric epithelial cells. By this interaction the unbound l-dopa concentration in bacterial suspension was strongly reduced. Conclusions This study suggests a potential in-vitro interaction of l-dopa with H. pylori adhesins, confirming the clinical changes found in pharmacokinetics of l-dopa therapy by H. pylori-positive patients with Parkinson's disease.