The Study On The Central Nervous Toxicity Of Ⅱ-Pyrethrins In Mice

OBJECTIVE: Pyrethrins is a new type pesticide that had developed rapidly in 1870s. It was refined from the plant at first. It can be divided into two types from its chemical structure: The type I has non-alpha-cyano which is represented by permethrin; The II contains alpha-cyano which is represented by deltamethrin and cypermethrin. Due to theirs high efficiency, broad-spectrum, low toxicity and low-residue advantages, they have been widely used to control pests in agriculture, forests, public places and in household. It was found that it is harm to people for its central nervou system toxicity,but the specific mechanism has not been thoroughly explained. This study is mainly to observe effects of II-pyrethroid pesticide on content of monoamine neurotransmitters in the brain in mice , the oxidative damage in mice' brain, the apoptosis in the mice' brain cells and the effects of protein expression of bcl-2 and p53. So that to explore toxicity of II-pyrethroid pesticide and injury mechaism of mice in central nervous system.METHODS: We used the chronic toxicity tests, and 210 Kunming mice were randomly divided into seven groups respectively (n=30). Deltamethrin (DM) 1.8mg/kg group, 2.7mg/kg group and 3.6mg/kg group, Cypermethrin (CP) 4.0mg/kg group, 6.0mg/kg group, 8.0mg/kg group and the salad oil control group.The changes of mice' weight and behaviour in every groups was observed in the periods of experiment.After treated by oral gavage for 30 days, the mice were fasting but drinking water free. 24 hours later, they were killed by cervical dislocation. The whole brains were peeled off, and weighted accurately. The fluorescence detect system of HPLC was used to detected content of Dopamine (DA), Norepinephrine (NE) and 5-Hydroxytryptamine (5-HT) in mice brain. And then we detected the effects of DM, CP to Maleic Dialdehyde (MDA),Hydroxyl radical (-OH),total antioxidant capacity (T-AOC) and Glutathione peroxidase (GSH-PX) activities in theirs brains. The immunohistochemical methods were used to detect the expression of bcl-2 and p53 in male mice brain.RESULTS:1 Effects of II-type pyrethroids on mice' pyrethroids, weight and organ coefficient: all the mice had tearing attacks, excitement and stimulation symptoms in varying degrees. And the DM groups were serious than the CP groups, while in the high dose groups were also serious than the low dose groups. The weight growth in the toxic groups were slower compared with the control group, and organ coefficient of the liver and spleen were incresed compared with the control group.And in the oppisite,the coefficient of brain were decresed compared with the control group.2 Effects of II-type pyrethroids on the content of monoamine neurotransmitters in the mice brain: the Dopamine (DA) levels in the four groups were all decreased than the control group and showed a downward trend in varying degrees, and there is a dose-response relationship between them; But 5'-Hydroxytryptamine (5'-HT) were not significantly changed compared with the control group. We also found the II-type pyrethroids can causes the MT content changed in mice brain, and in the toxic groups were deereased compared with the control group.3 The oxidative damage effects of II-type pyrethroids in the central nervous system of mice: the Maleic Dialdehyde (MDA),Hydroxyl radical (-OH) in four experimental groups were all increased than the control group. But the Total Antioxidant Ccapacity (T-AOC) and Glutathione Peroxidase (GSH-PX) activity were all decreased than the control group and showed a downward trend in varying degrees. Besides Hydroxyl radical (-OH), the other three targets were all had dose-effect relationship.4 The role of bcl-2 and p53 in the apoptosis mechanisms of neuronal cells induced by II-type pyrethroids: The bcl-2 protein expression in exposed mice' brain were decresed compared with the control group and the p53 protein expression were incresed compared with the control group.CONCLUSIONS: The perennial contacting of low concentration DM and CP may affect the monoamine contents of midbrains in the mice, and showed a downward trend in varying degrees. It can cause MDA,-OH, T-AOC and GSH-PX activity changes, result in antioxidant ability of the body decreased. It also can affect apoptosis and Bcl-2, P53 protein expression in the mice brain cells.