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Renal organic cation transporters mediated cadmium-induced nephrotoxicity

Sunhapas Soodvilai1, Jiriporn Nantavishit, Chatchai Muanprasat

  • 1Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok, Thailand. scsunhapas@mahidol.ac.th

Toxicology Letters
|April 26, 2011
PubMed

Insights

This study reveals that organic cation transporters 1 and 2 (OCT1 and OCT2) facilitate cadmium transport into kidney cells. Blocking these transporters with TEA reduces cadmium accumulation and toxicity in renal proximal tubules.

Area of Science:

  • Nephrology
  • Toxicology
  • Molecular Biology

Background:

  • Cadmium is a toxic heavy metal that can accumulate in the kidneys.
  • The mechanisms of cadmium transport into renal cells are not fully understood.
  • Organic cation transporters (OCTs) are known to transport various organic molecules across cell membranes.

Purpose of the Study:

  • To investigate the role of renal organic cation transporters (OCTs), specifically OCT1 and OCT2, in cadmium transport.
  • To determine if OCT1 and OCT2 mediate cadmium uptake into renal proximal tubular cells.
  • To assess the impact of cadmium transport via OCTs on renal cell toxicity.

Main Methods:

  • Utilized Chinese hamster ovary (CHO-K1) cells stably transfected with rabbit OCT1 and OCT2.
  • Examined cadmium transport in isolated murine renal proximal tubules and intact rat kidneys.
  • Measured the inhibition of [(3)H]-tetraethylammonium (TEA) uptake by cadmium to assess transporter activity.
  • Quantified cadmium accumulation in cells and kidney tissue.
  • Assessed cytotoxicity in OCT-expressing cells and the protective effect of TEA.

Main Results:

  • Cadmium inhibited TEA uptake mediated by both rbOCT1 and rbOCT2, with IC(50) values of 96±5μM and 207±12μM, respectively.
  • Cadmium accumulation was significantly higher in OCT-transfected cells compared to parent cells and was attenuated by TEA.
  • TEA administration reduced cadmium accumulation in whole rat kidneys.
  • Cadmium exposure induced cytotoxicity in OCT1- and OCT2-expressing cells, which was prevented by TEA treatment.

Conclusions:

  • Provides the first evidence that OCT1 and OCT2 mediate cadmium transport across the basolateral membrane into renal proximal tubular cells.
  • Suggests that OCT1 and OCT2 play a significant role in renal cadmium uptake and subsequent toxicity.
  • Highlights TEA as a potential agent to mitigate cadmium-induced renal damage by inhibiting OCT-mediated transport.

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