Submitted on July 28, 2007
Accepted on November 12, 2007
Effects of 
-Lipoic Acid on Ischemia/Reperfusion-Induced Renal Dysfunction in Rats
Eun Hui Bae1, Kyun Sang Lee1, JongUn Lee2, Seong Kwon Ma1, Nam Ho Kim1, Ki Chul Choi1, Jorgen Frokiaer3, Soren Nielsen3, Sun Young Kim4, Sung Zoo Kim4, Suhn Hee Kim4, and Soo Wan Kim1*
1 Chonnam National University Medical School, Department of Internal Medicine, Gwangju, Korea, Republic of
2 Chonnam National University Medical School, Department of Physiology, Gwangju, Korea, Republic of
3 University of Aarhus, The Water and Salt Research Center, Denmark
4 Chonbuk National University Medical School, Department of Physiology, Jeonju, Korea, Republic of
* To whom correspondence should be addressed. E-mail: skimw{at}chonnam.ac.kr.
We investigated whether 
-lipoic Acid (-LA), an antioxidant, attenuates the ischemia/reperfusion (I/R)-induced dysregulation of these transporters. Male Sprague-Dawley rats were clamped of both renal pedicles for 40 minutes. -LA (80 mg/kg) was administered intraperitoneally before and immediately after inducing the 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 polymerase chain reaction. 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 -1 subunit of Na,K-ATPase, NHE3, NKCC2 and NCC was markedly decreased in response to I/R. The expression of type VI adenylyl cyclase was decreased in I/R-injury rats, which was counteracted by the treatment of -LA. AVP-stimulated cAMP generation was blunted in I/R rats, which was then ameliorated by -LA treatment. -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 -LA. The cGMP generation in response to sodium nitroprusside was blunted in I/R rats, which was also significantly prevented by -LA. The mRNA expression of ET-1 was increased, which was recovered to the control level by -LA treatment. In conclusion, -LA treatment prevents I/R-induced dysregulation of AQPs and sodium transporters in the kidney, possibly through preserving normal activities of local AVP/cAMP, NO/cGMP and ET systems.
