The industrial chemical Tinuvin 123 does not induce dopaminergic neurotoxicity in C57Bl/6 mice.
We have investigated the acute effects of systemic administration of Tinuvin 123 on nigro-striatal dopaminergic neurons in the C57Bl/6 mouse. Tinuvin 123 was administered subcutaneously (s.c.) twice, 16 h apart, at doses of 0, 2, 20 or 200 mg/kg body weight to a total of 48 male C57Bl/6 mice (12 animals/group). Seven days following the last dose the animals were decapitated and the brains removed. No deaths occurred during the study. There were no differences between the mean body weights of any of the experimental groups prior to or following Tinuvin 123 treatment. Animals treated s.c. with 2 mg/kg Tinuvin 123 exhibited no changes in striatal dopamine or metabolite concentrations compared with vehicle-treated animals. Higher doses of Tinuvin 123 (20 and 200 mg/kg) resulted in a moderate loss of striatal dopamine (31 and 38%) but concentrations of the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid and the neurotransmitters serotonin, aspartate, gamma aminobutyric acid and glutamate were unchanged. The total number of tyrosine hydroxylase-immunoreactive neurons in the entire substantia nigra were equivalent in the vehicle- and Tinuvin 123-treated animals at all doses, thus no neuronal loss was demonstrated. In conclusion, this study demonstrates no evidence that systemic administered Tinuvin 123 induces dopaminergic neurotoxicity in C57Bl/6 mice.
Xiao
A Y
AY
Department of Psychiatry, University of Würzburg, Germany.
Double
K
K
Heinemann
T
T
Rausch
W D
WD
Riederer
P
P
Gerlach
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology* / Q000506:poisoning; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology* / Q000506:poisoning; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D003652:Decanoic Acids; D018377:Neurotransmitter Agents; D014677:Pharmaceutical Vehicles; D010880:Piperidines; D015102:3,4-Dihydroxyphenylacetic Acid; C083752:Tinuvin 770; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid