Skip to main content
SpringerLink
Log in

Rosiglitazone, peroxisome proliferator receptor-gamma agonist, ameliorates gentamicin-induced nephrotoxicity in rats

  • Urology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe gram-negative infections. Reactive oxygen spaces (ROS) are important mediators of gentamicin-induced nephrotoxicity. Peroxisome proliferator-activated receptors (PPARs) have different activities including antioxidant properties. This study was performed to investigate the protective role of PPAR-γ agonist against GEN-induced nephrotoxicity. Male Wistar Albino rats were randomly divided into the following four groups, each of which consisted of six animals: (1) control; (2) intraperitoneally injected with GEN for 14 consecutive days (100 mg/kg/day); (3) treatment with rosiglitazone (RSG) via nasogastric gavage (10 mg/kg/daily for 14 days); (4) treatment with GEN + RSG combination for 14 day. Rats were decapitated on the 15th day and kidneys were removed. Urine was collected for every 24 h for the determination of daily urine volume. Urea, creatinine, Na+ and K+ levels were measured in blood. Malondialdehyde (MDA), reduced glutathion (GSH), and nitric oxide (NO) levels along with glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activities were determined in the renal tissue. Changes in body weight were recorded. GEN treatment was found to cause nephrotoxicity as evidenced by elevation of serum urea and creatinine levels. Renal impairment was also assessed by the renal histology. The significant decrease in GSH and increases in MDA and NO levels as well as a decrease in GSH-Px, CAT, and SOD activities indicated that GEN-induced renal damage was mediated through oxidative reactions. On the other hand, RSG administration protected kidney tissue against GEN-induced and free radical-mediated oxidative renal damage in rats.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Humes HD, Weinberg JM (1986) Toxic nephropathies. In: Brenner BM, Rector FC (eds) The kidney. WB Saunders Co., Philadelphia, pp 1491–1532

    Google Scholar 

  2. Edson RS, Terrell CL (1999) The aminoglycosides. Mayo Clin Proc 74:519–528

    Article  CAS  PubMed  Google Scholar 

  3. Cuzzocrea S, Mazzon E, Dugo L et al (2002) A role for superoxide in gentamicin-mediated nephropathy in rats. Eur J Pharmacol 450:67–76

    Article  CAS  PubMed  Google Scholar 

  4. Yanagida C, Ito K, Komiya I et al (2004) Protective effect of fosfomycin on gentamicin-induced lipid peroxidation of rat renal tissue. Chem Biol Interact 148:139–147

    Article  CAS  PubMed  Google Scholar 

  5. Grune T, Sommerburg O, Petras T et al (1995) Postanoxic formation of aldehydic lipid peroxidation products in human renal tubular cells. Free Radic Biol Med 18:21–27

    Article  CAS  PubMed  Google Scholar 

  6. Baliga R, Ueda N, Walker PD et al (1999) Oxidant mechanisms in toxic acute renal failure. Drug Metab Rev 31:971–997

    Article  CAS  PubMed  Google Scholar 

  7. Winterbourn CC, Pichorner H, Kettle AJ (1997) Myeloperoxidase-dependent generation of a tyrosine peroxide by neutrophils. Arch Biochem Biophys 338:15–21

    Article  CAS  PubMed  Google Scholar 

  8. Fryer MJ (1997) Vitamin E may slow kidney failure owing to oxidative stress. Redox Rep 3:259–261

    CAS  PubMed  Google Scholar 

  9. Pedraza-Chaverrí J, Maldonado PD, Medina-Campos ON et al (2000) Garlic ameliorates gentamicin nephrotoxicity: relation to antioxidant enzymes. Free Radic Biol Med 29:602–611

    Article  PubMed  Google Scholar 

  10. Marx N, Bourcier T, Sukhova GK et al (1999) PPAR γ activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPAR γ as a potential mediator in vascular disease. Arterioscler Thromb Vasc Biol 19:546–551

    CAS  PubMed  Google Scholar 

  11. Cuzzocrea S, Mazzon E, Di Paola R et al (2006) The role of the peroxisome proliferator-activated receptor-α (PPAR-α) in the regulation of acute inflammation. J Leukoc Biol 79:999–1010

    Article  CAS  PubMed  Google Scholar 

  12. Toba H, Miki S, Shimizu T et al (2006) The direct antioxidative and anti-inflammatory effects of peroxisome proliferator-activated receptors ligands are associated with the inhibition of angiotensin converting enzyme expression in streptozotocin-induced diabetic rat aorta. Eur J Pharmacol 549:124–132

    Article  CAS  PubMed  Google Scholar 

  13. Liu D, Zeng BX, Zhang SH et al (2005) Rosiglitazone, an agonist of peroxisome proliferator-activated receptor γ, reduces pulmonary inflammatory response in a rat model of endotoxemia. Inflamm Res 54:464–470

    Article  CAS  PubMed  Google Scholar 

  14. Sánchez-Hidalgo M, Martín AR, Villegas I et al (2005) Rosiglitazone, an agonist of peroxisome proliferator-activated receptor γ, reduces chronic colonic inflammation in rats. Biochem Pharmacol 69:1733–1744

    Article  PubMed  Google Scholar 

  15. Abdelrahman M, Sivarajah A, Thiemermann C (2005) Beneficial effects of PPAR-γ ligands in ischemia–reperfusion injury, inflammation and shock. Cardiovasc Res 65:772–781

    Article  CAS  PubMed  Google Scholar 

  16. Villegas I, Martín AR, Toma W et al (2004) Rosiglitazone, an agonist of peroxisome proliferator-activated receptor γ, protects against gastric ischemia–reperfusion damage in rats: role of oxygen free radicals generation. Eur J Pharmacol 505:195–203

    Article  CAS  PubMed  Google Scholar 

  17. Wasowicz W, Neve J, Peretz A (1993) Optimized steps in fluorometric determination thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence sample preservation and storage. Clin Chem 39:2522–2528

    CAS  PubMed  Google Scholar 

  18. Beutler E (1975) Glutathione in red blood cell metabolism. A manual of biochemical methods. Grune and Stratton, New York, pp 112–114

    Google Scholar 

  19. Granger DL, Taintor RR, Boockvar KS et al (1999) Measurement of nitrate and nitrite in biological samples using nitrate reductase and Griess reaction. Methods Enzymol 268:142–151

    Article  Google Scholar 

  20. Paglia D, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–163

    CAS  PubMed  Google Scholar 

  21. Aebi H (1982) Catalase. In: Bergmeyer HU (ed) Methods in enzymatic analysis. Verlag Chemic, Weinheim, pp 273–282

    Google Scholar 

  22. Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500

    CAS  PubMed  Google Scholar 

  23. Allen CT (1992) Laboratory methods in histochemistry. In: Prophet EB, Mills B, Arrington JB, Sobin LH (eds) American registry of pathology, 1st edn. Washington DC, p 53

  24. Tariq M, Morais C, Sobki S et al (1999) N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats. Nephrol Dial Transplant 14:923–929

    Article  CAS  PubMed  Google Scholar 

  25. Humes HD (1988) Aminoglycoside nephrotoxicity. Kidney Int 33:900–911

    Article  CAS  PubMed  Google Scholar 

  26. Powell JH, Reidenberg MM (1983) Further studies of the response of kidney lysosomes to aminoglycosides and other cations. Biochem Pharmacol 32:3213–3220

    Article  CAS  PubMed  Google Scholar 

  27. Simmons CF Jr, Bogusky RT, Humes HD (1980) Inhibitory effects of gentamicin on renal mitochondrial oxidative phosphorylation. J Pharmacol Exp Ther 214:709–715

    CAS  PubMed  Google Scholar 

  28. Abdel-Gayoum AA, Bashir AA, el-Fakhri MM (1995) Effects of fish oil and sunflower oil supplementations on gentamicin-induced nephrotoxicity in rat. Hum Exp Toxicol 14:884–888

    Article  CAS  PubMed  Google Scholar 

  29. Kasiske BL, O’Donnell MP, Cleary MP et al (1989) Effects of reduced renal mass on tissue lipids and renal injury in hyperlipidemic rats. Kidney Int 35:40–47

    Article  CAS  PubMed  Google Scholar 

  30. Maegawa H, Nishio Y, Nakao K et al (2007) Short-term low-dosage pioglitazone treatment improves vascular dysfunction in patients with type 2 diabetes. Endocr J 54:613–618

    Article  CAS  PubMed  Google Scholar 

  31. Matsumoto T, Kakami M, Noguchi E et al (2007) Imbalance between endothelium-derived relaxing and contracting factors in mesenteric arteries from aged OLETF rats, a model of type 2 diabetes. Am J Physiol Heart Circ Physiol 293:H1480–H1490

    Article  CAS  PubMed  Google Scholar 

  32. Persson PB (2002) Nitric oxide in the kidney. Am J Physiol Regul Integr Comp Physiol 283:R1005–R1007

    PubMed  Google Scholar 

  33. Juncos LA, Garvin J, Carretero OA et al (1995) Flow modulates myogenic responses in isolated microperfused rabbit afferent arterioles via endothelium-derived nitric oxide. J Clin Invest 95:2478–2741

    Article  Google Scholar 

  34. Gabbai FB, Blantz RC (1999) Role of nitric oxide in renal hemodynamics. Semin Nephrol 19:242–250

    CAS  PubMed  Google Scholar 

  35. Pistrosch F, Herbrig K, Kindel B et al (2005) Rosiglitazone improves glomerular hyperfiltration, renal endothelial dysfunction, and microalbuminuria of incipient diabetic nephropathy in patients. Diabetes 54:2206–2211

    Article  CAS  PubMed  Google Scholar 

  36. Komers R, Vrána A (1998) Thiazolidinediones-tools for the research of metabolic syndrome X. Physiol Res 47:215–225

    CAS  PubMed  Google Scholar 

  37. Song J, Knepper MA, Hu X et al (2004) Rosiglitazone activates renal sodium- and water-reabsorptive pathways and lowers blood pressure in normal rats. J Pharmacol Exp Ther 308:426–433

    Article  CAS  PubMed  Google Scholar 

  38. Walker PD, Barri Y, Shah SV (1999) Oxidant mechanisms in gentamicin nephrotoxicity. Ren Fail 21:433–442

    Article  CAS  PubMed  Google Scholar 

  39. Yang CL, Du XH, Han YX (1995) Renal cortical mitochondria are the source of oxygen free radicals enhanced by gentamicin. Ren Fail 17:21–26

    Article  CAS  PubMed  Google Scholar 

  40. Ross D (1988) Glutathione, free radicals and chemotherapeutic agents. Mechanisms of free-radical induced toxicity and glutathione-dependent protection. Pharmacol Ther 37:231–249

    Article  CAS  PubMed  Google Scholar 

  41. McCord JM, Keele BB Jr, Fridovich I (1971) An enzyme-based theory of obligate anaerobiosis: the physiological function of superoxide dismutase. Proc Natl Acad Sci USA 68:1024–1027

    Article  CAS  PubMed  Google Scholar 

  42. Freeman BA, Crapo JD (1982) Biology of disease: free radicals and tissue injury. Lab Invest 47:412–426

    CAS  PubMed  Google Scholar 

  43. Lee S, Kim W, Moon SO et al (2006) Rosiglitazone ameliorates cisplatin-induced renal injury in mice. Nephrol Dial Transplant 21:2096–2105

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Bezm-i Alem Valide Sultan Vakif Gureba Research and Education Hospital, Aksaray, Istanbul, Turkey

    Emin Ozbek, Yusuf Ozlem Ilbey & Abdulmuttalip Simsek

  2. Department of Biochemistry, Kocaeli University Medical School, Istanbul, Turkey

    Mustafa Cekmen

  3. Department of Pediatrics, Bezm-i Alem Valide Sultan Vakif Gureba Research and Education Hospital, Istanbul, Turkey

    Fatih Mete

  4. Department of Pathology, Bezm-i Alem Valide Sultan Vakif Gureba Research and Education Hospital, Istanbul, Turkey

    Adnan Somay

Authors
  1. Emin Ozbek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yusuf Ozlem Ilbey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abdulmuttalip Simsek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mustafa Cekmen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fatih Mete
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Adnan Somay
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yusuf Ozlem Ilbey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ozbek, E., Ilbey, Y.O., Simsek, A. et al. Rosiglitazone, peroxisome proliferator receptor-gamma agonist, ameliorates gentamicin-induced nephrotoxicity in rats. Int Urol Nephrol 42, 579–587 (2010). https://doi.org/10.1007/s11255-009-9645-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-009-9645-7

Keywords

Search

Navigation