title: Effects of alpha-lipoic acid on ischemia-reperfusion-induced renal dysfunction in rats.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Hakdong 8, Gwangju 501-757, Korea.
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Bae
authors.forename: Kyun Sang
authors.initials: KS
authors.lastname: Lee
authors.forename: Jongun
authors.initials: J
authors.lastname: Lee
authors.forename: Seong Kwon
authors.initials: SK
authors.lastname: Ma
authors.forename: Nam Ho
authors.initials: NH
authors.lastname: Kim
authors.forename: Ki Chul
authors.initials: KC
authors.lastname: Choi
authors.forename: Jørgen
authors.initials: J
authors.lastname: Frøkiaer
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Sung Zoo
authors.initials: SZ
authors.lastname: Kim
authors.forename: Suhn Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Soo Wan
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D020346:Aquaporins / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D064466:Solute Carrier Family 12, Member 1; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D020346:Aquaporins; D019332:Endothelin-1; D018160:Receptors, Cytoplasmic and Nuclear; C578716:Slc12a1 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D009569:Nitric Oxide; D008063:Thioctic Acid; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP