Lipid bilayer-methotrexate interactions: A basis for methotrexateneurotoxicity

摘要

The anti-cancer drug, methotrexate has extensive applications in many chemotherapy regimens. However its use has been heavily restricted because of its severe neurotoxic side effects. The present work aims to identify a possible cause for these side effects, by studying the interaction of the drug on a model membrane system mimicking the lipid bilayer architecture of the cell membrane. The investigations led to the conclusion that the non-specific interaction of methotrexate with the lipid bilayer progressively fluidized the membrane architecture that ultimately resulted in its disintegration. The extent of damage caused to the lipid bilayer could be related to the severity of the adverse neuronal impairment caused by the drug.