Back to Search
Start Over
Low doses of ochratoxin A upregulate the protein expression of organic anion transporters Oat1, Oat2, Oat3 and Oat5 in rat kidney cortex.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2009 Sep 15; Vol. 239 (3), pp. 284-96. Date of Electronic Publication: 2009 Jun 16. - Publication Year :
- 2009
-
Abstract
- 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 microg OTA/kg b.m.) upregulated the abundance of all rOats, while a high dose (500 microg 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.
- Subjects :
- Animals
Blotting, Western
Dicarboxylic Acid Transporters biosynthesis
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Kidney Cortex metabolism
Kidney Cortex pathology
Kidney Tubules drug effects
Kidney Tubules metabolism
Kidney Tubules pathology
Lipid Peroxidation drug effects
Liver drug effects
Liver metabolism
Male
Ochratoxins pharmacokinetics
Ochratoxins urine
Organic Anion Transport Protein 1 biosynthesis
Organic Anion Transporters, Sodium-Independent biosynthesis
Oxidative Stress drug effects
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
Kidney Cortex drug effects
Ochratoxins toxicity
Organic Anion Transporters biosynthesis
Up-Regulation
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0333
- Volume :
- 239
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 19538982
- Full Text :
- https://doi.org/10.1016/j.taap.2009.06.008