title: 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.
authors: University of Defence, Hradec Kralove, Czech Republic. miroslav.pohanka@gmail.com
authors: Miroslav
authors: M
authors: Pohanka
authors: Filip
authors: F
authors: Zemek
authors: Hana
authors: H
authors: Bandouchova
authors: Jiri
authors: J
authors: Pikula
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000470:Alkaloids / Q000633:toxicity*; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001806:Blood Urea Nitrogen; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005980:Glutathione Reductase / Q000378:metabolism; D006168:Guinea Pigs; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D018570:Risk Assessment; D012717:Sesquiterpenes / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D018675:Toxicity Tests
chemical_list: D000470:Alkaloids; D015415:Biomarkers; D001786:Blood Glucose; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D012717:Sesquiterpenes; D017392:Thiobarbituric Acid Reactive Substances; C050426:huperzine A; D005980:Glutathione Reductase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3