Roles of Organic Anion Transporters in the Progression of Chronic Renal Failure

Ischemic acute renal failure (iARF) was described to reduce renal extraction of the organic anion para-aminohippurate (PAH) in humans. The rate-limiting step of renal organic anion secretion is its basolateral uptake into proximal tubular cells. This process is mediated by the organic anion transporters OAT1 and OAT3, which both have a broad spectrum of substrates including a variety of pharmaceutics and toxins. Using a rat model of iARF, we investigated whether impairing the secretion of the organic anion PAH might be associated with downregulation of OAT1 or OAT3. Inulin and PAH clearance was determined starting from 6 up to 336 h after ischemia-reperfusion (I/R) injury. Net secretion of PAH was calculated and OAT1 as well as OAT3 expression was analyzed by RT-PCR and Western blotting. Inulin and PAH clearance along with PAH net secretion were initially diminished after I/R injury with a gradual recovery during follow-up. This initial impairment after iARF was accompanied by decreased mRNA and protein levels of OAT1 and OAT3 in clamped animals compared with sham-operated controls. In correlation to the improvement of kidney function, both mRNA and protein levels of OAT1 and OAT3 were upregulated during the follow-up. Thus decreased expression of OAT1 and OAT3 is sufficient to explain the decline of PAH secretion after iARF. As a result, this may have substantial impact on excretion kinetics and half-life of organic anions. As a consequence, the biological effects of a variety of organic anions may be affected after iARF.

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Downregulation of organic anion transporters in rat kidney under ischemia/reperfusion-induced qacute renal failure

Kidney International ◽

10.1038/sj.ki.5002104 ◽

2007 ◽

Vol 71 (6) ◽

pp. 539-547 ◽

Cited By ~ 63

Author(s):

T. Matsuzaki ◽

H. Watanabe ◽

K. Yoshitome ◽

T. Morisaki ◽

A. Hamada ◽

...

Keyword(s):

Renal Failure ◽

Rat Kidney ◽

Ischemia Reperfusion ◽

Organic Anion ◽

Organic Anion Transporters ◽

Anion Transporters

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Correction to "Downregulation of organic anion transporters in rat kidney under ischemia/reperfusion-induced qacute renal failure"

Kidney International ◽

10.1038/sj.ki.5002216 ◽

2007 ◽

Vol 71 (10) ◽

pp. 1079

Keyword(s):

Renal Failure ◽

Rat Kidney ◽

Ischemia Reperfusion ◽

Organic Anion ◽

Organic Anion Transporters ◽

Anion Transporters

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Arsenic and Mercury Containing Traditional Chinese Medicine (Realgar and Cinnabar) Strongly Inhibit Organic Anion Transporters, Oat1 and Oat3,In Vivoin Mice

BioMed Research International ◽

10.1155/2015/863971 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Wen-Hao Yu ◽

Na Zhang ◽

Jin-Feng Qi ◽

Chen Sun ◽

Yong-Hui Wang ◽

...

Keyword(s):

Heavy Metals ◽

Renal Failure ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Organic Anion ◽

Pharmacokinetic Parameters ◽

Organic Anion Transporters ◽

Toxic Heavy Metals ◽

Anion Transporters

Toxic heavy metals, including mercury (Hg) and arsenic (As), accumulate preferentially in kidneys and always cause acute renal failure. The aim of this study was to investigate whether these samples affect organic anion transporters, Oat1 and Oat3,in vivoin mice kidney. Mice (n=10) were orally treated with investigational samples. After last administration, all mice were i.v.p-aminohippuric acid (PAH), and the blood and kidneys samples were collected. The concentrations of PAH were quantified by spectrophotometry. mRNA expressions of Oat1 and Oat3 were assayed by real-time PCR. In comparison with corresponding control, major pharmacokinetic parameters of PAH in sera were significantly changed by investigational samples (p<0.05), PAH accumulations in the kidney tissues were significantly higher (p<0.05), PAH uptake by renal slices was greatly reduced, Oat1 and Oat3 mRNA expression were significantly inhibited in investigational sample groups. Arsenic and mercury containing traditional Chinese medicine (Realgar and Cinnabar) probably induce kidney damage through inhibiting several members of the organic anion transporters (such as OAT1 and OAT3).

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