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Low doses of ochratoxin A upregulate the protein expression of organic anion transporters Oat1, Oat2, Oat3 and Oat5 in rat kidney cortex (CROSBI ID 136128)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Žlender, Vilim ; Breljak, Davorka ; Ljubojević, Marija ; Flajs, Dubravka ; Balen, Daniela ; Brzica, Hrvoje ; Domijan, Ana-Marija ; Peraica, Maja ; Fuchs, Radovan ; Anzai, Naohiko et al. Low doses of ochratoxin A upregulate the protein expression of organic anion transporters Oat1, Oat2, Oat3 and Oat5 in rat kidney cortex // Toxicology and applied pharmacology, 239 (2009), 3; 284-296. doi: 10.1016/j.taap.2009.06.008

Podaci o odgovornosti

Žlender, Vilim ; Breljak, Davorka ; Ljubojević, Marija ; Flajs, Dubravka ; Balen, Daniela ; Brzica, Hrvoje ; Domijan, Ana-Marija ; Peraica, Maja ; Fuchs, Radovan ; Anzai, Naohiko ; Sabolić, Ivan

engleski

Low doses of ochratoxin A upregulate the protein expression of organic anion transporters Oat1, Oat2, Oat3 and Oat5 in rat kidney cortex

Mycotoxin ochratoxin A (OTA) is nephrotoxic in various animal species. In rodents, OTA intoxication impairs various proximal tubule (PT) functions, including secretion of p-aminohippurate (PAH), possibly via affecting the renal organic anion (OA) transporters (Oat). However, an effect of OTA on the activity/expression of specific Oats in the mammalian kidney has not been reported. In this work, male rats were gavaged various doses of OTA every 2nd day for 10 days, and in their kidneys we studied: tubule integrity by microscopy, abundance of basolateral (rOat1, rOat3) and brush border (rOat2, rOat5) rOat proteins by immunochemical methods, and expression of rOats mRNA by RT-PCR. The OTA treatment caused: a) dose-dependent damage of the cells in S3 segments of medullary rays, b) dual effect upon rOats in PT: low doses (50-250 ug OTA/kg b.m.) upregulated the abundance of all rOats, while a high dose (500 ug OTA/kg b.m.) downregulated the abundance of rOat1, and c) unchanged mRNA expression for all rOats at low OTA doses, and its downregulation at high OTA dose. Changes in the expression of renal Oats were associated with enhanced OTA accumulation in tissue and excretion in urine, whereas the indicators of oxidative stress either remained unchanged (malondialdehyde, glutathione, 8-hydroxydeoxyguanosine) or became deranged (microtubules). While OTA accumulation and downregulation of rOats in the kidney are consistent with the previously reported impaired renal PAH secretion in rodents intoxicated with high OTA doses, the post-transcriptional upregulation of Oats at low OTA doses may contribute to OTA accumulation and development of nephrotoxicity.

kidney; membrane transporters; mycotoxins; nephrotoxicity; organic anions; PAH; proximal tubule

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

Podaci o izdanju

239 (3)

2009.

284-296

objavljeno

0041-008X

10.1016/j.taap.2009.06.008

Povezanost rada

Temeljne medicinske znanosti

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