Low doses of ochratoxin A upregulate the protein expression of organic anion transporters Oat1, Oat2, Oat3 and Oat5 in rat kidney cortex
- Unit of Toxicology, Institute for Medical Research and Occupational Health, Zagreb (Croatia)
- Molecular Toxicology, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR-10001, Zagreb (Croatia)
- Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo (Japan)
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 {mu}g OTA/kg b.m.) upregulated the abundance of all rOats, while a high dose (500 {mu}g 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.
- OSTI ID:
- 21272654
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 239, Issue 3; Other Information: DOI: 10.1016/j.taap.2009.06.008; PII: S0041-008X(09)00244-0; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses
Gene expression changes induced by ochratoxin A in renal and hepatic tissues of male F344 rat after oral repeated administration