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Jørgen Frøkiær

Effects of alpha-lipoic acid on ischemia-reperfusion-induced renal dysfunction in rats

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  • Eun Hui Bae, Denmark
  • Kyun Sang Lee, Denmark
  • Jongun Lee, Denmark
  • Seong Kwon Ma, Denmark
  • Nam Ho Kim, Denmark
  • Ki Chul Choi, Denmark
  • Jørgen Frøkiaer
  • Søren Nielsen, Denmark
  • Sun Young Kim, Denmark
  • Sung Zoo Kim, Denmark
  • Suhn Hee Kim, Denmark
  • Soo Wan Kim, Denmark
  • Department of Anatomy
  • Biomedical Radio Isotope Techniques
We investigated whether alpha-lipoic acid (alpha-LA), an antioxidant, attenuates the ischemia-reperfusion (I/R)-induced dysregulation of these transporters. Both renal pedicles of male Sprague-Dawley rats were clamped for 40 min. alpha-LA (80 mg/kg) was administered intraperitoneally before and immediately after induction of ischemia. After 2 days, the expression of aquaporins (AQPs), sodium transporters, and nitric oxide synthases (NOS) was determined in the kidney by immunoblotting and immunohistochemistry. The expression of endothelin-1 (ET-1) mRNA was determined by real-time PCR. Activities of adenylyl cyclase and guanylyl cyclase were measured by stimulated generation of cAMP and cGMP, respectively. The expression of AQP1-3 as well as that of the alpha(1)-subunit of Na-K-ATPase, type 3 Na/H exchanger, Na-K-2Cl cotransporter, and Na-Cl cotransporter was markedly decreased in response to I/R. The expression of type VI adenylyl cyclase was decreased in I/R-injured rats, which was counteracted by the treatment of alpha-LA. AVP-stimulated cAMP generation was blunted in I/R rats and was then ameliorated by alpha-LA treatment. alpha-LA treatment attenuated the downregulation of AQPs and sodium transporters. The expression of endothelial NOS was decreased in I/R rats, which was prevented by alpha-LA. The cGMP generation in response to sodium nitroprusside was blunted in I/R rats, which was also significantly prevented by alpha-LA. The mRNA expression of ET-1 was increased, which was recovered to the control level by alpha-LA treatment. In conclusion, alpha-LA treatment prevents I/R-induced dysregulation of AQPs and sodium transporters in the kidney, possibly through preserving normal activities of local AVP/cAMP, nitric oxide/cGMP, and ET systems.
Original languageEnglish
JournalAmerican Journal of Physiology: Renal Physiology
Pages (from-to)F272-80
Publication statusPublished - 2007

    Research areas

  • Adenylate Cyclase, Animals, Antioxidants, Aquaporins, Cyclic GMP, Endothelin-1, Guanylate Cyclase, Kidney, Male, Models, Animal, Nitric Oxide, Rats, Rats, Sprague-Dawley, Receptors, Cytoplasmic and Nuclear, Reperfusion Injury, Sodium-Hydrogen Antiporter, Sodium-Potassium-Chloride Symporters, Sodium-Potassium-Exchanging ATPase, Thioctic Acid

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