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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
Author(s) -
Chan Melissa P. L.,
Morisawa Shinsuke,
Nakayama Aki,
Kawamoto Yuko,
Yoneda Minoru
Publication year - 2006
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.20175
Subject(s) - endosulfan , neurotoxicity , chemistry , cytotoxicity , blood–brain barrier , toxicity , in vitro , toxicology , biophysics , biology , biochemistry , pesticide , endocrinology , central nervous system , organic chemistry , agronomy
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 α‐endosulfan, β‐endosulfan, or endosulfan sulfate. Cytotoxicity testing revealed that the three endosulfans did not cause cell death at concentrations of 10 μM and below. The ratio of the average permeability of the filter‐grown endothelial cell monolayer to 14 C‐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 μM. α‐Endosulfan, β‐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 α‐endosulfan were highly selective, with a wide range of LC 50 values found in the different cultures, ranging from 11.2 μM for CCF‐STTG1 cells to 48.0 μM for PC12 cells. In contrast, selective neurotoxicity was not so manifest in glial and neuronal cell cultures after exposure to endosulfan sulfate, as LC 50 values were in the range of 10.4–21.6 μM. CCF‐STTG1 cells were more sensitive to α‐endosulfan and endosulfan sulfate, whereas NT2 cells were more sensitive to β‐endosulfan. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 223–235, 2006.