Effect of bis (tributyl tin) oxide on permeability of the blood-brain barrier: a transient increase.
OBJECTIVE
To study the effect of bis (tributyl tin) oxide (TBTO) on permeability of the blood-brain barrier.


METHODS
Electron microscopy and an x ray microanalyser with lanthanum chloride as a tracer were used, and blood tin concentrations were determined with an atomic absorption spectrophotometer. Adult male wistar rats received 0.05 ml/kg body weight of TBTO orally.


RESULTS
A transient increase in paracellular permeability at the blood-brain barrier was found 2 h after the dose of TBTO. Electron dense lanthanum deposits penetrated tight junctions of the endothelia and permeated the subendothelial space. The x ray microprobe data showed an accumulation of TBTO at the tight junctions at 2 h. Leakage of tracer did not occur at 4 h, but oedematous changes in the surrounding glial cells were prominent between 4 and 8 h and had almost returned to normal by 24 h. By atomic absorption analysis, it was seen that blood tin concentrations rapidly increased at 1 h and rose to a maximum peak at 8 h, then gradually decreased to reach zero at 24 h.


CONCLUSIONS
Accumulated TBTO at tight junctions could have caused the temporary replacement of calcium ion by tin, which induces a transient increase in paracellular permeability throughout the blood-brain barrier.
Department of Anatomy, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
K
K
Hara
M
M
Yoshizuka
Y
Y
Doi
S
S
Fujimoto
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007365:Intercellular Junctions / Q000187:drug effects*; D008297:Male; D008854:Microscopy, Electron; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D013054:Spectrophotometry, Atomic; D013997:Time Factors; D014220:Trialkyltin Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D007166:Immunosuppressive Agents; D014220:Trialkyltin Compounds; C005961:bis(tri-n-butyltin)oxide