Electrolyte Blood Press.  2007 Jun;5(1):23-27. 10.5049/EBP.2007.5.1.23.

Effects of Antioxidant Drugs in Rats with Acute Renal Injury

• Bae EH
• Lee JU
• Kim SW

• KMID: 2134801
• DOI: http://doi.org/10.5049/EBP.2007.5.1.23

Abstract

Acute renal failure is mainly caused by ischemia/reperfusion (I/R) injury or nephrotoxic drugs, in which reactive oxygen species (ROS) may play an important role. Therefore, antioxidants are expected to decrease the vulnerability of renal injury associated with oxidative challenges. alpha-Lipoic acid (alpha-LA), potent antioxidant, could act as ROS scavengers, iron chelators and enzyme modulators. In rats with acute renal injury, dysregulation of aquaporin (AQP) water channels and sodium transporters has been noted. I/R injury or cisplatin induced marked down-regulation of AQP1, AQP2 and AQP3 water channels, and type-3 Na-H exchanger, Na,K-ATPase, and Na-K-2Cl cotransporters, in association with impairment of urinary concentration and tubular sodium reabsorption. Treatment with alpha-LA prevented the dysregulation of AQP channels and sodium transporters, along with improved urinary concentrating capability and renal sodium reabsorption.

MeSH Terms

Acute Kidney Injury*
Animals
Antioxidants
Aquaporins
Chelating Agents
Cisplatin
Down-Regulation
Iron
Rats*
Reactive Oxygen Species
Reperfusion Injury
Sodium
Thioctic Acid
Antioxidants
Aquaporins
Chelating Agents
Cisplatin
Iron
Reactive Oxygen Species
Sodium
Thioctic Acid

Figure

• 

  Fig. 1 The balance of the oxidative stress and defence system.

Reference

1. Kim SW, Jeon YS, Lee JU, Kang DG, Kook H, Ahn KY, Kim SZ, Cho KW, Kim NH, Han JS, Choi KC. Diminished adenylate cyclase activity and aquaporin 2 expression in acute renal failure rats. Kidney Int. 2000; 57:1643–1650. PMID: 10760099.

2. Johnston PA, Rennke H, Levinsky NG. Recovery of proximal tubular function from ischemic injury. Am J Physiol. 1984; 246:F159–F166. PMID: 6364844.

3. Tanner GA, Sloan KL, Sophasan S. Effects of renal artery occlusion on kidney function in the rat. Kidney Int. 1973; 4:377–389. PMID: 4780267.

4. Vetterlein F, Petho A, Schmidt G. Distribution of capillary blood flow in rat kidney during postischemic renal failure. Am J Physiol. 1986; 251:H510–H519. PMID: 3752265.

5. Vogt BA, Shanley TP, Croatt A, Alam J, Johnson KJ, Nath KA. Glomerular inflammation induces resistance to tubular injury in the rat. A novel form of acquired, heme oxygenase-dependent resistance to renal injury. J Clin Invest. 1996; 98:2139–2145. PMID: 8903334.

6. Vaya J, Aviram M. Nutritional antioxidant: mechanisms of action, analyses of activities and medical applications. Curr Med Chem-Imm Endoc & Metab Agent. 2001; 1:99–117.

7. Fryer MJ. Vitamin E may slow kidney failure owing to oxidative stress. Redox Rep. 1997; 3:259–261. PMID: 9754323.

8. Packer L, Roy S, Sen CK. A-lipoic acid: a metabolic antioxidant and potential redox modulator of transprition. Adv Pharmacol. 1997; 38:79–101. PMID: 8895805.

9. Packer L, Witt EH, Tritschler HJ. alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med. 1995; 19:227–250. PMID: 7649494.

10. Sung MJ, Kim W, Ahn SY, Cho CH, Koh GY, Moon SO, Kim DH, Lee S, Kang KP, Jang KY, Park SK. Protective effect of alpha-lipoic acid in lipopolysaccharideinduced endothelial fractalkine expression. Circ Res. 2005; 97:880–890. PMID: 16166554.

11. Sabolic I, Valenti G, Verbavatz JM, Van Hoek AN, Verkman AS, Ausiello DA, Brown D. Localization of the CHIP28 water channel in rat kidney. Am J Physiol. 1992; 263:C1225–C1233. PMID: 1282299.

12. Ma T, Yang B, Gillespie A, Carlson EJ, Epstein CJ, Verkman AS. Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels. J Biol Chem. 1998; 273:4296–4299. PMID: 9468475.

13. Yamamoto T, Sasaki S, Fushimi K, Ishibashi K, Yaoita E, Kawasaki K, Marumo F, Kihara I. Vasopressin increases AQP-CD water channel in apical membrane of collecting duct cells in Brattleboro rats. Am J Physiol. 1995; 268:C1546–C1551. PMID: 7541941.

14. Kashgarian M, Biemesderfer D, Caplan M, Forbush B 3rd. Monoclonal antibody to Na,K-ATPase: immunocytochemical localization along nephron segments. Kidney Int. 1985; 28:899–913. PMID: 3003443.

15. Kim SW, Wang W, Kwon TH, Knepper MA, Frokiaer J, Nielsen S. Increased expression of ENaC subunits and increased apical targeting of AQP2 in the kidneys of spontaneously hypertensive rats. Am J Physiol Renal Physiol. 2005; 289:F957–F968. PMID: 15956775.

16. Kim SW, Wang W, Nielsen J, Praetorius J, Kown TH, Knepper MA, Frokiaer J, Nielsen S. Increased expression and apical targeting of renal ENaC subunits in puromycin aminonucleoside-induced nephrotic syndrome in rats. Am J Physiol Renal Physiol. 2004; 286:F922–F935. PMID: 15075188.

17. Kwon TH, Frokiaer J, Han JS, Knepper MA, Nielsen S. Decreased abundance of major Na(+) transporters in kidneys of rats with ischemia-induced acute renal failure. Am J Physiol Renal Physiol. 2000; 278:F925–F939. PMID: 10836980.

18. Kwon TH, Frokiaer J, Fernandez-Llama P, Knepper MA, Nielsen S. Reduced abundance of aquaporins in rats with bilateral ischemia-induced acute renal failure: prevention by alpha-MSH. Am J Physiol. 1999; 277:F413–F427. PMID: 10484525.

19. Massy ZA, Guijarro C, O'Donnell MP, Kim Y, Kashtan CE, Egido J, Kasiske BL, Keane WF. The central role of nuclear factor-kappa B in mesangial cell activation. Kidney Int Suppl. 1999; 56(71):S76–S79. PMID: 10412743.

20. Lebwohl D, Canetta R. Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. Eur J Cancer. 1998; 34:1522–1534. PMID: 9893623.

21. Goldstein RS, Mayor GH. Minireview. The nephrotoxicity of cisplatin. Life Sci. 1983; 32:685–690. PMID: 6338333.

22. Choie DD, Longnecker DS, del Campo AA. Acute and chronic cisplatin nephropathy in rats. Lab Invest. 1981; 44:397–402. PMID: 7194946.

23. Dobyan DC, Levi J, Jacobs C, Kosek J, Weiner MW. Mechanism of cis-platinum nephrotoxicity: II. Morphologic observations. J Pharmacol Exp Ther. 1980; 213:551–556. PMID: 7193726.

24. Ecelbarger CA, Sands JM, Doran JJ, Cacini W, Kishore BK. Expression of salt and urea transporters in rat kidney during cisplatin-induced polyuria. Kidney Int. 2001; 60:2274–2282. PMID: 11737600.

25. Kim SW, Lee JU, Nah MY, Kang DG, Ahn KY, Lee HS, Choi KC. Cisplatin decreases the abundance of aquaporin water channels in rat kidney. J Am Soc Nephrol. 2001; 12:875–882. PMID: 11316845.

26. Takaoka M, Ohkita M, Kobayashi Y, Yuba M, Matsumura Y. Protective effect of alpha-lipoic acid against ischaemic acute renal failure in rats. Clin Exp Pharmacol Physiol. 2002; 29:189–194. PMID: 11906481.

27. Garcia NH, Pomposiello SI, Garvin JL. Nitric oxide inhibits ADH-stimulated osmotic water permeability in cortical collecting ducts. Am J Physiol. 1996; 270:F206–F210. PMID: 8769841.

28. Yu L, Gengaro PE, Niederberger M, Burke TJ, Schrier RW. Nitric oxide: a mediator in rat tubular hypoxia/reoxygenation injury. Proc Natl Acad Sci U S A. 1994; 91:1691–1695. PMID: 7510405.

29. Frokiaer J, Marples D, Knepper MA, Nielsen S. Bilateral ureteral obstruction downregulates expression of vasopressin-sensitive AQP-2 water channel in rat kidney. Am J Physiol. 1996; 270:F657–F668. PMID: 8967344.

30. Frokiaer J, Christensen BM, Marples D, Djurhuus JC, Jensen UB, Knepper MA, Nielsen S. Downregulation of aquaporin-2 parallels changes in renal water excretion in unilateral ureteral obstruction. Am J Physiol. 1997; 273:F213–F223. PMID: 9277582.