A Preliminary Study On The Mechanisms Of Cypermethrin Immunotoxicity

Pyrethroid pesticides are widely used as substitutes for orgnaophosphorus and organochlorine, especially for household sanitation purposes. Therefore, human beings are confronted with increasing pyrethroids exposure risk and, their toxicity assessment is essential. However, studies on pyrethroid pesticides toxicity generally focused on their neurological effects which underlied their major symptoms; while their immunological counterparts are usually ignored thus in-depth studies are more needed.Cypermethrin is a representative of the synthetic pyrethroids. Besides its pesticidal activity, cypermethrin has been sold and used as specific inhibitor of calcineurin for decades with hundreds of papers approving this effect. Calcineurin has been implicated in several signaling pathways correlating with immune system, thus studies on immunological effects of cypermethrin might shed light on the mechanisms for all pyrethroid pesticides immunotoxicity.Fish species are lower vertebrates and are suggested to playing special roles in innate immunity; moreover, they are more sensitive to pyrethroid pesticides than other model organisms. Zebrafish has been recommended by OECD as laboratory animal for exogenous compounds toxicity assessment, thus utilized in this study as well.Cypermethrin had been applied to zebrafish and the LC50 value was determined between 10μg/L and 18μg/L. After a 96-hour intoxication, relative-quantitive RT-PCR method was employed to detect the relative transcriptional levels of the molecules involved in NFAT signaling and Wnt signaling pathways. The specific GSK3βblocking agent Li₂CO₃ was also used alone or in combination with cypermethrin and the same method was practiced.It was shown that Li₂CO₃ alone inhibited gsk3βtranscription; cypermethrin upregulated both rcan1 and il-1β; while the il-1βupregulation extent by both drugs was higher than any one worked separately. Contrary to anticipation, the supposed calcineurin specific inhibitor cypermethrin should have upregulated il-1β; thus it was inferred that this process might be correlated with cytoplasmic influx of Ca₂⁺ rather than calcineurin inhibition by cypermethrin. It was also presented in this study that Li₂CO₃ acts on whole body zebrafish results in gsk3βexpression inhibition, consistent with the studies on cultured intact cells. On the whole, nfat and wnt signaling pathways might be integrated in cypermethrin immune regulation effects, and Li₂CO₃ might facilitate cypermethrin action.Due to limited research, most common immunological proteins and their antibodies are commercially unavailable for zebrafish researchers. Furthermore, antibodies from other organisms cross react poorly with corresponding antigens from zebrafish. None the less, some preliminary results on the mechanisms of cypermethrin immunotoxicity have been achieved; and further studies are indicated in the future with more zebrafish specific reagents developed.