engleski

Ochratoxin A treatment in rats changes the expression of basolateral anion transporters OAT1 and OAT3 in renal proximal tubules

A mycotoxin ochratoxin A (OTA) is nephrotoxic and primarily targets proximal tubules (PT). It has been shown that OTA inhibits the transport of p-aminohyppurate (PAH) in PT, and that secretion of both OTA and PAH is mediated by organic anion transporters OAT1 & OAT3 that reside in the PT cell basolateral membrane (BLM). The possibility that OAT1 and OAT3 may be involved in OTA nephrotoxicity has not been clarified. In order to study the expression of OAT1 and OAT3 along the nephron in an in vivo experimental model of OTA nephrotoxicity, adult male rats were treated with different OTA doses (50-500 ug/kg, every 2nd day, p.o.) for 10 days. The expression of OATs was studied by Western blotting in total cell membranes isolated from the renal tissues, and by immunocytochemistry in tissue cryosections. The specific protein bands were evaluated by densitometry. OTA caused a dose-dependent damage of the PT S3 segments in medullary rays. As shown by both immunochemical methods, lower OTA doses significantly increased, whereas higher doses strongly decreased the abundance/expression of both OATs in BLM along the PT, whereas the content of actin remained unchanged. These OTA effects were visible only in the cortical tubules.

nephrotoxicity; mammalian kidney; organic anion transporters; protein expression

nije evidentirano