CIS-Bifenthrin Enantioselectivly Induces The Toxicity Of Oxidative And Immune System In Mice

As a synthetic pyrethroid pesticide, bifenthrin (BF), is used widely to control field and household pests. As a kind of chiral pesticide, in China, the commercial cis-BF contained two enantiomers including 1R-cis-BF and 1S-cis-BF. cis-BF is widely used in the form of raceme, it caused more attention in the pollution of the environment and human security issues, as well as its toxicity of chiral. The aims of the presnet experiment are to evaluate the oxidative stress and immunotoxicity induced by cis-BF in mice.Firstly, we evaluated the toxicity of BF on oxidative and immune system in mice. Adolescent and adult male ICR mice were orally administered BF for 3 weeks at doses of 10 and 20mg/kg/day. Both the weights of the spleen and the thymus decreased significantly in the adolescent mice when they were treated with 20mg/kg BF for three weeks. And the mRNA levels of TNFa and IL2 in the spleen and IL2 as well as IL4 in the thymus of puberty mice increased after oral administration of BF for 3 weeks. Meanwhile the total antioxidant capacity (T-AOC) and the activity of superoxide dismutase (SOD) were altered significantly. Hepatic GSH content increased significantly in both the adolescent and adult mice exposed to 20mg/kg BF.Secondly, we suggested that BF has the potential to induce immunotoxicity accompanied by oxidative stress, especially in puberty mice. In the study of the enantioselectivly on oxidative stress in mice, the hepatic ROS levels, as well as the MDA and GSH content both in the serum and liver increased significantly in the 4 or 6 weeks 1S-cis-BF treated groups at dose of 5mg/kg/day. Moreover, the transcription of oxidative stress response related genes including Sodl, Cat and Ho-1 in the liver of 1S-cis-BF treated group was also significant higher than those in 1R-cis-BF treated group. Thus, it concluded that cis-BF induced hepatic oxidative stress in an enantiomer specific manner in mice, and that 1S-cis-BF showed much more toxic in hepatic oxidative stress than 1R-cis-BF.Finally, we evaluated cis-BF enantioselectivly on the toxic ity of immune system in mice from in vivo and in vitro experimental system. In vivo experiment, the mRNA levels of TNFa, IL-1α, IL-2, IL-4 in the spleen increased after oral administration of 1S-cis-BF at doses of 15 mg/kg/day. More importantly, 1S-cis-BF treated groups were significant higher than those in 1R-cis-BF treated group. In vitro experiment, the RAW264.7 cell viability and NO level decreased significantly and the activity of LDH increased significantly in the 1S-cis-BF treated groups at doses of 10-5 mol/L. Moreover, the mRNA levels of TNFa, IL-6 and IL-8 decreased significantly. The results of the present study suggested that cis-BF enantioselectivly induced the toxic ity of immune system in mice, and that 1S-cis-BF showed much more toxic than 1R-cis-BF.In conclution, cis-BF induced oxidative stress and immunotoxicity in an enantiomer specific manner in mice. These data were helpful to understand the toxicity of commercially used cis-BF in mammals under the enantiomeric level.