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Effects of alpha-lipoic acid on ischemia-reperfusion-induced renal dysfunction in rats.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2008 Jan; Vol. 294 (1), pp. F272-80. Date of Electronic Publication: 2007 Nov 21. - Publication Year :
- 2008
-
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.
- Subjects :
- Adenylyl Cyclases metabolism
Animals
Aquaporins metabolism
Cyclic GMP metabolism
Endothelin-1 metabolism
Guanylate Cyclase metabolism
Kidney drug effects
Kidney metabolism
Male
Models, Animal
Nitric Oxide metabolism
Rats
Rats, Sprague-Dawley
Receptors, Cytoplasmic and Nuclear metabolism
Reperfusion Injury metabolism
Sodium-Hydrogen Exchanger 3
Sodium-Hydrogen Exchangers metabolism
Sodium-Potassium-Chloride Symporters metabolism
Sodium-Potassium-Exchanging ATPase metabolism
Soluble Guanylyl Cyclase
Solute Carrier Family 12, Member 1
Antioxidants pharmacology
Kidney physiopathology
Reperfusion Injury prevention & control
Thioctic Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1931-857X
- Volume :
- 294
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 18032550
- Full Text :
- https://doi.org/10.1152/ajprenal.00352.2007