Expression of renal organic anion transporters OAT1 and OAT3 in ochratoxin A-treated rats (CROSBI ID 520161)
Prilog sa skupa u časopisu | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Žlender, Vilim ; Ljubojević, Marija ; Balen, Daniela ; Breljak, Davorka ; Anzai, Naohiko ; Fuchs, Radovan ; Sabolić, Ivan
engleski
Expression of renal organic anion transporters OAT1 and OAT3 in ochratoxin A-treated rats
Introduction. Ochratoxin A (OTA), a mycotoxin produced by several Aspergillus and Penicillium species, is nephrotoxic, hepatotoxic, teratogenic and immunotoxic. In the mammalian kidney, OTA primarily targets proximal tubules (PT). Studies have shown that in PT OTA inhibits the transport of p-aminohyppurate (PAH) and that the secretion of both OTA and PAH is mediated by organic anion transporters OAT1 & OAT3 (subfamily of SLC22 drug transporters) that reside in the PT basolateral membrane (BLM). These findings indicate that OAT1 & OAT3 may be involved in OTA nephrotoxicity, but this possibility has not been clarified. Methods. To study cell morphology and expression of OAT1 & OAT3 along the nephron in an in vivo experimental model of OTA nephrotoxicity, adult male rats were treated with different OTA doses (0, 50, 125, 250 or 500 µ ; ; ; ; ; ; g/kg, every 2nd day, p.o.) for 10 days. Using specific antibodies, OATs were studied by Western blotting (WB) in total cell membranes (TCM) isolated from the pooled cortex (C) and outer stripe (OS) tissues, and by immunocytochemistry (IC) in tissue cryosections. The specific protein bands were evaluated densitometrically. Results. OTA caused a dose-dependent damage (cell desquamation and degradation) of the PT S3 segments in medullary rays. In WB of TCM, at lower or higher OTA doses the respective OAT1 content significantly increased (~50% at 125 µ ; ; ; ; ; ; g/kg) or strongly decreased (~70 % at 500 µ ; ; ; ; ; ; g/kg). The content of OAT3 exhibited a strong, dose-dependent increase, reaching maximum (~300% above the controls) at 125-250 µ ; ; ; ; ; ; g/kg. The content of actin in TCM remained unchanged. IC showed heterogeneous OAT1 staining in the PT BLM which strongly diminished in rats treated with 500 µ ; ; ; ; ; ; g OTA/kg, whereas OAT3 staining in the C and OS tubules matched the respective WB data. At 500 µ ; ; ; ; ; ; g OTA/kg, a dramatic loss of OAT3 was observed in the heavily-damaged S3 segments in medullary rays. Conclusions. OTA treatment in rats causes: a) dose-dependent cell damage in S3 in medullary rays, and b) dual effect on renal OAT1 an OAT3: low doses upregulate and high doses downregulate the expression of these transporters in the cortical tubules.
Mycotoxin; Proximal tubule; Nephrotoxicity
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Podaci o prilogu
Vol. 164S, S81-x.
2006.
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Podaci o matičnoj publikaciji
Toxicology letters
Kniewald, Jasna
Amsterdam: Elsevier
0378-4274
Podaci o skupu
43rd Congress of the European Societies of Toxicology and 6th Congress of Toxicology in Developing Countries
poster
20.09.2006-24.09.2006
Cavtat, Hrvatska