title: Development of an in vitro blood-brain barrier model to study the effects of endosulfan on the permeability of tight junctions and a comparative study of the cytotoxic effects of endosulfan on rat and human glial and neuronal cell cultures.
abstract: Endosulfan, an organochlorine (OC) insecticide that belongs to the cyclodiene group, is one of the most commonly used pesticides to control pests in vegetables, cotton, and fruits. Porcine brain microvascular endothelial cells were used to develop a model to study the effects of endosulfan on the permeability of tight junctions in the blood-brain barrier (BBB). BBB permeability, measured as transendothelial electrical resistance, decreased in a dose- and time-dependent manner when treated with alpha-endosulfan, beta-endosulfan, or endosulfan sulfate. Cytotoxicity testing revealed that the three endosulfans did not cause cell death at concentrations of 10 microM and below. The ratio of the average permeability of the filter-grown endothelial cell monolayer to 14C-endosulfan (Pe) going from the outer to the inner compartments with that going from the inner to the outer compartments was approximately 1:1.2-2.1 after exposure to concentrations of 0.01-10 microM. alpha-Endosulfan, beta-endosulfan, and endosulfan sulfate had cytotoxic effects on rat glial (C6) and neuronal (PC12) cell cultures as well as on human glial (CCF-STTG1) and neuronal (NT2) cell cultures. The effects of alpha-endosulfan were highly selective, with a wide range of LC50 values found in the different cultures, ranging from 11.2 microM for CCF-STTG1 cells to 48.0 microM for PC12 cells. In contrast, selective neurotoxicity was not so manifest in glial and neuronal cell cultures after exposure to endosulfan sulfate, as LC50 values were in the range of 10.4-21.6 microM. CCF-STTG1 cells were more sensitive to alpha-endosulfan and endosulfan sulfate, whereas NT2 cells were more sensitive to beta-endosulfan.
authors.affiliation: Department of Global Environment Engineering, Graduate School of Engineering, Kyoto University, Yoshida-honmachi, Sakyo-ku, Kyoto 606-8501, Japan. melissa@risk.env.kyoto-u.ac.jp
authors.forename: Melissa P L
authors.initials: MP
authors.lastname: Chan
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Morisawa
authors.forename: Aki
authors.initials: A
authors.lastname: Nakayama
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawamoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoneda
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D004726:Endosulfan / Q000633:toxicity*; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D008954:Models, Biological; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010539:Permeability; D051381:Rats; D013997:Time Factors
chemical_list: D002250:Carbon Radioisotopes; D007306:Insecticides; D004726:Endosulfan