Toxicological scoring of Alzheimer’s disease drug huperzine in a guinea pig model

Abstract

Huperzine is a secondary metabolite in lycopods Huprzia and an inhibitor of acetylcholinesterase and antagonist of N-methyl-D-apartate receptor. Huperine is a suitable drug for the treatment of Alzheimer’s disease as it is a part of traditional Chinese medicine. Currently, it undergoes clinical trials in the European Union and United States. The toxicological data about huperzine are missing and link between huperzine and oxidative stress has not been extensively investigated. For the above mentioned reasons, we organized experiment on a guinea pig model aimed at the investigation of adverse effects caused by huperzine. Guinea pigs were exposed to (–)-huperzine A in doses 5–625 µg/kg. Animals were sacrificed one day after exposure. Ferric reducing antioxidant power, thiobarbituric acid reactive substances, glutathione reductase, caspase 3 activity and selected biochemical markers (e.g. transaminases, blood urea nitrogen and glucose) were assayed. In frontal, parietal, temporal lobes and cerebellum, we found increase of antioxidants, glutathione reductase and oxidative stress markers in a dose dependent manner. Effects on liver, kidney and spleen were milder. We discuss ambivalent action of huperzine in the body and judge the huperzine action owing to recently reported experiments.

Keywords::

• Huperzine
• Alzheimer’s disease
• acetylcholinesterase
• NMDA receptor
• oxidative stress

Acknowledgements

The Faculty of Military Health Sciences, University of Defense is gratefully acknowledged for the specific research project “Assay of biochemical and pharmacokinetic parameters of selected inhibitors of acetylcholinesterase”.

Declaration of interest

The Ministry of Defence of the Czech Republic is gratefully acknowledged for the project No. OVUOFVZ200802.