Influence of Magnetic Resonance Contrast Media on the Activity of Histamine Inactivating Enzymes

Abstract

The observation that the intravenous application of gadolinium-based contrast media can lead to nephrogenic systemic fibrosis (NSF) has raised interest in their interactions with pathways. In this context, histamine is a focus because of its stimulating effect on fibrogenesis. In humans, histamine can be inactivated either by diamine oxidase (DAO) or by histamine N-methyltransferase (HMT), and numerous drugs are known to inhibit these enzymes. Therefore, it was the aim of this study to investigate whether magnetic resonance imaging contrast agents have an inhibitory effect on the enzymatic activities of DAO and HMT. Seven gadolinium-based (gadoterate meglumine, gadoteridol, gadobutrol, gadobenate dimeglumine, gadopentetate dimeglumine, gadoxetate disodium, gadodiamide) and one manganese-containing (mangafodipir) contrast agents were tested in vitro. Following the preincubation of purified DAO and HMT with 0.1 to 10 mmol/L of the respective contrast medium, enzyme activities were determined using radiometric microassays. Enzyme activities measured in the absence of contrast agents and after preincubation with specific inhibitors of DAO and HMT, respectively, served as controls. The gadolinium-containing and manganese-containing contrast media tested did not show significant inhibition of the activities of DAO and HMT. No significant difference was observed between ionic and nonionic or between cyclic and linear gadolinium compounds. Preincubation of the enzymes with specific inhibitors led to complete inhibition of the respective enzymatic activity. The gadolinium-containing and manganese-based magnetic resonance imaging contrast media tested did not exhibit significant inhibition of histamine-inactivating enzymes at physiologically relevant concentrations.