Skip to main content
Log in

Comparison of the effects of l-carnitine and α-tocopherol on acute ureteral obstruction-induced renal oxidative imbalance and altered energy metabolism in rats

  • Original Paper
  • Published:
Urological Research Aims and scope Submit manuscript

Abstract

The suppression of renal energy metabolism during ureteral obstruction is a well-known phenomenon; however, its exact responsible mechanism(s) and association with simultaneously induced renal oxidative stress have not been clarified. This study examined the improving effects of l-carnitine, a facilitating cofactor for mitochondrial oxidation of fatty-acids as well as a scavenger of free-radicals, and α-tocopherol as the most potent antioxidant on renal metabolic defect and oxidative stress induced by acute unilateral ureteral obstruction (UUO). The left ureter was ligated in ether-anaesthetised rats, in which l-carnitine, α-tocopherol or their vehicles were intraperitoneally injected in four different groups. After elapsing 24 h of UUO-induction, both kidneys were removed and stored at −80°C. There were also two sham-operated and control groups. The kidney samples were assessed to measure the levels of ferric reducing/antioxidant power (FRAP) and malondialdehyde (MDA) for evaluating their redox state, as well as, their amounts of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) by using luciferin–luciferase method. As much as 24 h of UUO in vehicle-treated groups caused increases in MDA and ADP, but decreases in FRAP, ATP, and ATP/ADP of the obstructed kidney with respect to those of the sham group. α-tocopherol normalised the levels of MDA and FRAP but did not affect the altered amounts of energy metabolic indices in the obstructed kidney, while l-carnitine could ameliorate all of them. These findings suggest that oxidative stress may not involve in development of acute UUO-induced suppression of renal aerobic metabolism, and probably reduction of energy substrates is a responsible factor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Klahr S (2008) Obstructive uropathy. In: Alpern RJ, Hebert SC (eds) Seldin and Giebisch’s the kidney—physiology and pathology, 4th edn. Academic press, Elsevier, pp 2247–2282

    Google Scholar 

  2. Ricardo SD, Ding G, Eufemio M, Diamond JR (1997) Antioxidant expression in experimental hydronephrosis: role of mechanical stretch and growth factors. Am J Physiol 272:F789–F798

    CAS  PubMed  Google Scholar 

  3. Klahr S (2001) Urinary tract obstruction. Semin Nephrol 21:133–145

    Article  CAS  PubMed  Google Scholar 

  4. Modi KS, Morrissey J, Shah SV, Schreiner GF, Klahr S (1990) Effects of probucol on renal function in rats with bilateral ureteral obstruction. Kidney Int 38:843–850

    Article  CAS  PubMed  Google Scholar 

  5. Saborio P, Ward K, Chan W, Krieg RJ Jr, Lin KC, Chan JCM (1999) Oxidation of lipoprotein in injury and repair of obstructive nephropathy. Clin Exp Nephrol 3:254–260

    Article  CAS  Google Scholar 

  6. Akin M, Demirbilek S, Ay S, Gurunluogh K, Turkmen E, Tas E, Aksoy RF, Baykarabulut A, Edali MN (2007) Attenuation of ureteral obstruction-induced renal injury by polyenylphosphatidylcholine. Int J Urol 14:350–356

    Article  CAS  PubMed  Google Scholar 

  7. Kamijo-Ikemori A, Sugaya T, Obama A, Hiroi J, Miura H, Watanabe M, Kumai T, Ohtani-Kaneko R, Hirata K, Kimura K (2006) Liver-type fatty-acid-binding protein attenuates renal injury induced by unilateral ureteral obstruction. Am J Pathol 169:1107–1117

    Article  CAS  PubMed  Google Scholar 

  8. O’Connor PM (2006) Renal oxygen delivery: matching delivery to metabolic demand. Clin Exp Pharmacol Physiol 33:961–967

    Article  PubMed  Google Scholar 

  9. Klahr S, Schwab SJ, Stokes TJ (1986) Metabolic adaptations of the nephron in renal disease. Kidney Int 29:80–89

    Article  CAS  PubMed  Google Scholar 

  10. Schirmer HKA, Murphy GP, Taft JL, Scott WW (1967) Urine flow and renal metabolism following prolonged complete ureteral occlusion. J Urol 97:1000–1002

    CAS  PubMed  Google Scholar 

  11. Schirmer HKA, Marshall RE (1968) Metabolism of atrophic renal tissue following removal of complete ureteral obstruction. J Urol 100:596–597

    CAS  PubMed  Google Scholar 

  12. Blondin J, Purkerson ML, Rolf D, Schoolwerth AC, Klahr S (1975) Renal function and metabolism after relief of unilateral ureteral obstruction. Proc Soc Exp Biol Med 150:71–76

    CAS  PubMed  Google Scholar 

  13. Nito H, Descoeudres C, Kurokawa K, Massry SG (1978) Effect of unilateral obstruction on renal cell metabolism and function. J Lab Clin Med 91:60–71

    CAS  PubMed  Google Scholar 

  14. Cruthirds DL, Novak L, Akhi KM, sanders PW, Thompson JA, MacMillan-Crow LA (2003) Mitochondrial targets of oxidative stress during renal ischemia/reperfusion. Arch Biochem Biophys 412:27–33

    Article  CAS  PubMed  Google Scholar 

  15. Du Y, Ko KM (2005) Effects of emodin treatment on mitochondrial ATP generation capacity and antioxidant components as well as susceptibility to ischemia-reperfusion injury in rat hearts: single versus multiple doses and gender difference. Life Sci 77:2770–2782

    Article  CAS  PubMed  Google Scholar 

  16. Hurtado O, De Cristobal J, Sanchez V, Lizasoain I, Cardenas A, Pereira MP, Colado MI, Leza JC, Lorenzo P, Moro MA (2003) Inhibition of glutamate release by delaying ATP fall accounts for neuroprotective effects of antioxidants in experimental stroke. FASEB J 17:2082–2084

    CAS  PubMed  Google Scholar 

  17. Packer L, Weber SU, Rimbach G (2001) Molecular aspects of α-tocotrienol action and cell signalling. J Nutr 131:369S–373S

    CAS  PubMed  Google Scholar 

  18. Traber MG, Atkinson J (2007) Vitamin E, antioxidant and nothing more. Free Radic Biol Med 43:4–15

    Article  CAS  PubMed  Google Scholar 

  19. Guarnieri G, Biolo G, Toigo G, Situlin R (2003) Carnitine in renal failure. In: Kopple JD, Massry SG (eds) Kopple and Massry’s nutritional management of renal disease, 2nd edn. Lippincott Williams & Wilkins, Philadelphia, pp 357–368

    Google Scholar 

  20. Gulcin I (2006) Antioxidant and antiradical activities of l-carnitine. Life Sci 78:803–811

    Article  PubMed  Google Scholar 

  21. Ergun O, Ulman C, Kilicalp AS, Ulman I (2001) Carnitine as a preventive agent in experimental renal ischemia-reperfusion injury. Urol Res 29:186–189

    Article  CAS  PubMed  Google Scholar 

  22. Sener G, Paskaloglu K, Satiroglu H, Alican I, Kacmaz A, Sakarcan A (2004) l-carnitine ameliorates oxidative damage due to chronic renal failure in rats. J Cardiovasc Pharmacol 43:698–705

    Article  CAS  PubMed  Google Scholar 

  23. Harris RH, Yager WE (1974) Renal function after release of unilateral ureteral obstruction in rats. Am J Physiol 227:806–815

    CAS  PubMed  Google Scholar 

  24. Arreola-Mendoza L, Reyes JL, Melendez E, Martin D, Namorado MC, Sanchez E, Del Razo LM (2006) Alpha-tocopherol protects against the renal damage caused by potassium. Toxicology 218:237–246

    CAS  PubMed  Google Scholar 

  25. Bjorneboe A, Bjorneboe GE, Drevon CA (1987) Serum half-life, distribution, hepatic uptake and biliary excretion of alpha-tocopherol in rats. Biochim Biophys Acta 921:175–181

    CAS  PubMed  Google Scholar 

  26. Avunduk MC, Yurdakul T, Erdemil E, Yavus A (2003) Prevention of renal damage by alpha tocopherol in ischemia and reperfusion models of rats. Urol Res 31:280–285

    Article  CAS  PubMed  Google Scholar 

  27. Varskeviciene ZZ, Cerniauskiene RC, Grybauskas PS (1984) Effect of alpha-tocopherol on the production of malondialdehyde in rat tissue homogenates after hypobaric exposure. Gen Physiol Biophys 3:47–53

    CAS  PubMed  Google Scholar 

  28. Evans AM, Fornasini G (2003) Pharmacokinetics of l-carnitine. Clin Pharmacokinet 42:941–967

    Article  CAS  PubMed  Google Scholar 

  29. Benzie IFF, Strain JJ (1999) Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid. Methods Enzymol 299:15–27

    Article  CAS  PubMed  Google Scholar 

  30. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  31. Lundin A (2000) Use of firefly luciferase in ATP-related assays of biomass, enzymes, and metabolites. Methods Enzymol 305:346–370

    Article  CAS  PubMed  Google Scholar 

  32. Alipour BS, Hosseinkhani S, Nikkhah M, Naderi-Manesh H, Chaichi MJ, Kazempour Osaloo S (2004) Molecular cloning, sequence analysis, and expression of a cDNA encoding the luciferase from the glow-worm, lampyris turkestanicus. Biochem Biophys Res Commun 325:215–222

    Article  PubMed  Google Scholar 

  33. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  34. Vaughan ED Jr, Marion D, Poppas DP, Felsen D (2004) Pathophysiology of unilateral ureteral obstruction: Studies from Charlottesville to New York. J Urol 172:2563–2569

    Article  CAS  PubMed  Google Scholar 

  35. Li C, Wang W, Kwon TH, Knepper MA, Nielsen S, Frokiaer J (2003) Altered expression of major renal Na transporters in rats with unilateral ureteral obstruction. Am J Physiol Renal Physio 284:F155–F166

    CAS  Google Scholar 

  36. Aslan A, Karaguzel G, Gungor F, Izgut-Uysal N, Aydin F, Melikoglu M (2003) The effects of pentoxifylline on renal function and free radical production in unilateral ureteral obstruction. Urol Res 31:317–322

    Article  CAS  PubMed  Google Scholar 

  37. Moriyama T, Kawada N, Nagatoya K, Takeji M, Horio M, Ando A, Imai E, Hori M (2001) Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction. Kidney Int 59:2095–2103

    CAS  PubMed  Google Scholar 

  38. Kone BC (2008) Metabolic basis in solute transport. In: Brenner BM, Levine SA (eds) Brenner and Rector’s the kidney, 8th edn. Saunders, Elsevier, pp 130–155

    Google Scholar 

  39. Reilly PM, Schiller HJ, Bulkley GB (1991) Pharmacological approach to tissue injury mediated by free radicals and other reactive oxygen metabolites. Am J Surg 161:488–503

    Article  CAS  PubMed  Google Scholar 

  40. Kashyap MK, Yadav V, Sherawat BS, Jain S, Kumari S, Khullar M, Sharma PC, Nath R (2005) Different antioxidants status, total antioxidant power and free radicals in essential hypertension. Mol Cell Biochem 277:89–99

    Article  CAS  PubMed  Google Scholar 

  41. Nath KA, Croatt AJ, Hostetter TH (1990) Oxygen consumption and oxidant stress in surviving nephrons. Am J Physiol 258:F1354–F1362

    CAS  PubMed  Google Scholar 

  42. Kheir-Eldin AA, Motawi TK, Gad MZ, Abd-ElGawad HM (2001) Protective effect of vitamin-E, beta-carotene and N-acetylcysteine from the brain oxidative stress induced in rats by lipopolysaccharide. Int J Biochem Cell Biol 33:475–482

    Article  CAS  PubMed  Google Scholar 

  43. Cimen B, Turkozkan N, Unlu A, Erbil MK (2005) Effects of melatonin on 3-nitrotyrosine formation and energy charge ratio in guinea pig kidney in LPS-induced stress. Cell Biochem Funct 23:273–277

    Article  CAS  PubMed  Google Scholar 

  44. Krarup PM, Stolle LB, Rawashdeh YF, Skott O, Djurhuus JC, Frokiaer J (2007) Regional changes in renal cortical glucose, lactate and urea during acute unilateral ureteral obstruction. Scand J Urol Nephrol 41:47–53

    Article  CAS  PubMed  Google Scholar 

  45. Tannenbaum J, Pukerson ML, Klahr S (1983) Effect of unilateral ureteral obstruction on metabolism of renal lipids in the rat. Am J Physiol 245:F254–F262

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the Research Council of Shiraz University (Medical Sciences), Shiraz, Iran for the financial support of this study (grant number: 84-2434). The authors state no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Mostafa Shid Moosavi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moosavi, S.M.S., Ashtiyani, S.C., Hosseinkhani, S. et al. Comparison of the effects of l-carnitine and α-tocopherol on acute ureteral obstruction-induced renal oxidative imbalance and altered energy metabolism in rats. Urol Res 38, 187–194 (2010). https://doi.org/10.1007/s00240-009-0238-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00240-009-0238-9

Keywords

Navigation