Carcinogenesis, Teratogenesis & Mutagenesis ›› 2017, Vol. 29 ›› Issue (4): 251-255.doi: 10.3969/j.issn.1004-616x.2017.04.002

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Induction of dopaminergic neuron degeneration by atrazine in substantia nigra in adolescent rats

MA Kun1, WU Haoyu1, LI Peng1, WANG Li2, LI Baixiang1   

  1. 1. Department of Toxicology, Public Health College of Harbin Medical University, Harbin 150081;
    2. School Hospital, Harbin University of Commerce, Harbin 150028, Heilongjiang, China
  • Received:2016-11-17 Revised:2017-04-10 Online:2017-07-31 Published:2017-07-31

Abstract:

OBJECTIVE: To study effects of atrazine (ATR) on neuronal degeneration in adolescent rats. METHODS: 4 weeks old Wistar male rats were randomly subdivided into 4 groups:control and ATR test groups. All rats were treated with ATR:50,100 and 200 mg/kg body weight per day (five times per week) for 45 days by oral gavage. They were sacrificed at 12 h after the last ATR injection. The entire midbrain was collected and stored frozen at -80℃. The presence of tyrosine hydroxylase(TH) was detected by immunohistochemistry SP in dopaminergic neurons. TH expression in mRMA and protein was measured using real-time PCR and Western blot. RESULTS: Immunohistochemical results showed that,compared with the control group,the number of TH positive cells in the 200 mg/kg ATR group was significantly decreased (P < 0.01). In addition,qPCR results show that expression of TH mRNA and Bcl-2 mRNA was significantly decreased in the 100 and 200 mg/kg ATR groups,and expression of p53 mRNA and Caspase-9 mRNA was significantly increased in the 200 mg/kg ATR group,the difference was statistically significant (P < 0.05). Western blot results show that expression of TH and Bcl-2 protein was significantly decreased in the 100 and 200 mg/kg ATR groups compared with the control group. Expression of p53 protein in the ATR group was significantly increased at 100 and 200 mg/kg,and Caspase-9 protein in he 200 mg/kg ATR group was significantly increased,the difference was statistically significant (P < 0.05). CONCLUSION: Atrazine caused damage to the dopaminergic neurons in the substantia nigra of rats and activated the apoptotic pathway which led to the dopaminergic neuronal death.

Key words: atrazine, dopaminergic neurons, immunohistochemistry, tyrosine hydroxylase

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