Tacrine is implicated in oxidative stress in the laboratory guinea pig model.
OBJECTIVE
Tacrine was the first acetylcholinesterase inhibitor approved for the treatment of Alzheimer disease. The compound is not available for therapeutic purposes as it was withdrawn due to hepatotoxicity of its metabolites. The hepatotoxicity can be decreased by alternative ways of drug administration avoiding thus the first pass effect. The present study is aimed to investigate the influence of intramuscularly administrated tacrine on oxidative stress.


METHODS
Laboratory guinea pigs were exposed to tacrine at doses of 0-800 μg/kg. The animals were euthanized 1 and 24 hours after the exposure. Parameters such as ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS), carbonylated proteins, caspase 3 activity, superoxide dismutase activity and glutathione reductase activity were assessed in the frontal, temporal and occipital lobe, cerebellum, liver, spleen, heart, and kidney. Moreover, levels of glucose, total and HDL cholesterol forms, triglycerides, blood urea nitrogen, creatinine, total bilirubin, total protein, albumin and activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase were assessed in plasma samples.


RESULTS
Activities of the enzymatic markers, level of carbonylated proteins in organs and levels of biochemical markers in plasma were only slightly influenced by tacrine. Dose-dependent elevation of the FRAP value was recognized in the brain tissues and the liver. The TBARS value was increased in the kidney and heart 1 and 24 hours, respectively, after exposure.


CONCLUSIONS
In the study, the effect of tacrine on markers of oxidative stress was proved. Possible positive effects of tacrine on the antioxidant defence in the brain tissue were discussed.
Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
Alzbeta
A
Kracmarova
Hana
H
Bandouchova
Jiri
J
Pikula
Miroslav
M
Pohanka
D000544:Alzheimer Disease / Q000139:chemically induced* / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D013619:Tacrine / Q000633:toxicity*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D013619:Tacrine; D053148:Caspase 3