Tyrosine hydroxylase as a target for deltamethrin in the nigrostriatal dopaminergic pathway.
OBJECTIVE
To study the effects of deltamethrin on tyrosine hydroxylase in nigrostriatum of male rats.


METHODS
Sprague-Dawley rats were daily treated with deltamethrin at 6.25 or 12.5 mg/kg body weight by gavage for 10 days. Then HPLC-fluorescence detection was used to analyze the contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homoranillic acid (HVA) in substantial nigra and striatum. The activities of tyrosine hydroxylase (TH) were also detected by HPLC-fluorescence detection. TH mRNA or TH protein levels were measured by RT-PCR and immunohistochemistry method.


RESULTS
The content of DA in striatum was significantly decreased by the treatments, suggesting an inhibition of DA synthesis by deltamethrin. The contents of DA metabolites DOPAC and HVA increased, indicating increased dopamine turnover. Furthermore, deltamethrin significantly decreased the activity, as well as the mRNA and protein levels of TH.


CONCLUSIONS
These findings reveal a novel aspect of deltamethrin neurotoxicity and suggest tyrosine hydroxylase as a molecular target of deltamethin on dopamine metabolism in the nigrostriatal pathway.
Liu
Gong-Ping
GP
Department of Toxicology, MOE key Laboratory of Environmental and Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Ma
Qiang
Q
Shi
Nian
N