Effects of bile duct ligation on function and expression of OCT1/2 on the blood-brain barrier in rats and their mechanisms

This study investigated the effects of bile duct ligation (BDL)-induced liver injury on the function and expression of organic cation transporter 1/2 (OCT1/2) at blood brain barrier (BBB) and their potential mechanisms. BDL rat model was constructed, and physiological and biochemical parameters, BBB integrity, cortical OCT1/2 protein expression and function, and plasma chenodeoxycholic acid (CDCA) level were then examined by kits, Western blot, and LC-MS. Physiological and biochemical parameters, plasma bile acid levels, and cortical OCT1/2 protein expression were determined in rats after ig administration of CDCA for 14 d. The results showed that serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels increased, plasma CDCA level increased, the brain-to-blood concentration ratio (Kp) of amantadine decreased, while cortical Claudin-5 and Occludin did not significantly change, OCT1 expression was downregulated, while OCT2 did not significantly change in BDL rats. Serum AST, ALT, and ALP levels did not significantly change, plasma CDCA level increased, cortical OCT1 expression was downregulated, and OCT2 did not significantly change in rats after ig administration of CDCA. This study suggests that downregulation of OCT1 function and expression at BBB of BDL rats is related to elevated CDCA in plasma.