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Molecular and Cellular Biochemistry

, Volume 308, Issue 1–2, pp 35–42 | Cite as

Renoprotective effect of Erdosteine in rats against gentamicin nephrotoxicity: a comparison of 99mTc-DMSA uptake with biochemical studies

  • Mehmet Cabuk
  • Ahmet Gurel
  • Feyza Sen
  • Nejat Demircan
Article

Abstract

Erdosteine is a mucolytic agent having antioxidant properties through its active metabolites in acute injuries induced by pharmacological drugs. This study was designed to investigate the renoprotective potential of Erdosteine against gentamicin (GM)-induced renal dysfunction by using Technetium-99 m dimercaptosuccinic acid (Tc-99 m DMSA) uptake and scintigraphy in rats. For this purpose, male Wistar rats were randomly allotted into one of the four experimental groups: Control, Erdosteine, GM, and GM + Erdosteine groups. GM and GM + Erdosteine groups received 100 mg/kg GM intramuscularly for 6 days. In addition, Erdosteine and GM + Erdosteine groups received 50 mg/kg Erdosteine orally for 6 days. Renal function tests were assessed by serum blood urea nitrogen (BUN), creatinine levels, as well as scintigraphic and tissue radioactivity measurements with Tc-99 m DMSA. Renal oxidative damage was determined by renal malondialdehyde (MDA) levels, by antioxidant enzyme activities; superoxide dismutase (SOD) and catalase (CAT) and activities of oxidant enzymes; xanthine oxidase (XO) and myeloperoxidase (MPO). GM administration resulted in marked renal lipid peroxidation, increased XO and MPO activities and decreased antioxidant enzyme activities. GM + Erdosteine group significantly had lower MDA levels, higher SOD and CAT activities and lower XO and MPO activities, when compared to GM. Also GM + Erdosteine had lower levels of serum BUN, creatinine and higher renal tissue Tc-99 m DMSA uptake and radioactivity with respect to GM. In conclusion, our results supported a protective role of Erdosteine in nephrotoxicity associated with GM treatment.

Keywords

Erdosteine Gentamicin Nephrotoxicity Oxidative stress Tc-99m DMSA 

References

  1. 1.
    Ho JL, Barza M (1987) Role of aminoglycoside antibiotics in the treatment of intra-abdominal infection. Antimicrob Agents Chemother 31:485–491PubMedGoogle Scholar
  2. 2.
    Lerner SA, Schmitt BA, Seligsohn R, Matz GJ (1986) Comparative study of ototoxicity and nephrotoxicity in patients randomly assigned to treatment with amikacin or gentamicin. Am J Med 80:98–104PubMedCrossRefGoogle Scholar
  3. 3.
    Rodriguez-Barbero A, Lopez-Novoa JM, Arevalo M (1997) Involvement of platelet-activating factor in gentamicin nephrotoxicity in rats. Exp Nephrol 5:47–54PubMedGoogle Scholar
  4. 4.
    Cuzzocrea S, Mazzon E, Dugo L, Serraino I, Di PR, Britti D, De SA, Pierpaoli S, Caputi A, Masini E et al (2002) A role for superoxide in gentamicin-mediated nephropathy in rats. Eur J Pharmacol 450:67–76PubMedCrossRefGoogle Scholar
  5. 5.
    Halliwell B, Gutteridge JM (1984) Lipid peroxidation, oxygen radicals, cell damage, and antioxidant therapy. Lancet 1:1396–1397PubMedCrossRefGoogle Scholar
  6. 6.
    Halliwell B (1997) Antioxidants and human disease: a general introduction. Nutr Rev 55:S44–S49PubMedCrossRefGoogle Scholar
  7. 7.
    Dechant KL, Noble S (1996) Erdosteine. Drugs 52:875–881PubMedCrossRefGoogle Scholar
  8. 8.
    Gurel A, Armutcu F, Cihan A, Numanoglu KV, Unalacak M (2004) Erdosteine improves oxidative damage in a rat model of renal ischemia-reperfusion injury. Eur Surg Res 36:206–209PubMedCrossRefGoogle Scholar
  9. 9.
    Piepsz A (2002) Radionuclide studies in paediatric nephro-urology. Eur J Radiol 43:146–153PubMedCrossRefGoogle Scholar
  10. 10.
    Yamada M (1991) Assessment of 99mTc-DMSA renography and uptake compared with creatinine clearance in rats with drug-induced nephrotoxicity—I. Gentamicin-induced nephrotoxicity. Kaku Igaku 28:339–345PubMedGoogle Scholar
  11. 11.
    Yamada M (1991) Assessment of 99mTc-DMSA renography and uptake compared with creatinine clearance in rats with drug-induced nephrotoxicity—II. Cisplatin-induced nephrotoxicity. Kaku Igaku 28:347–354PubMedGoogle Scholar
  12. 12.
    Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431PubMedCrossRefGoogle Scholar
  13. 13.
    Prajda N, Weber G (1975) Malignant transformation-linked imbalance: decreased xanthine oxidase activity in hepatomas. FEBS Lett 59:245–249PubMedCrossRefGoogle Scholar
  14. 14.
    Aebi (1974) Catalase. New York and London Academic PressGoogle Scholar
  15. 15.
    Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500PubMedGoogle Scholar
  16. 16.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  17. 17.
    Ekor M, Farombi EO, Emerole GO (2006) Modulation of gentamicin-induced renal dysfunction and injury by the phenolic extract of soybean (Glycine max). Fundam Clin Pharmacol 20:263–271PubMedCrossRefGoogle Scholar
  18. 18.
    Farombi EO, Ekor M (2006) Curcumin attenuates gentamicin-induced renal oxidative damage in rats. Food Chem Toxicol 44:1443–1448PubMedCrossRefGoogle Scholar
  19. 19.
    Inglesi M, Nicola M, Fregnan GB, Bradamante S, Pagani G (1994) Synthesis and free radical scavenging properties of the enantiomers of erdosteine. Farmaco 40:703–708PubMedGoogle Scholar
  20. 20.
    Miyake K, Kaise T, Hosoe H, Akuta K, Manabe H, Ohmori K (1999) The effect of erdosteine and its active metabolite on reactive oxygen species production by inflammatory cells. Inflamm Res 48:205–209PubMedCrossRefGoogle Scholar
  21. 21.
    Hayashi K, Hosoe H, Kaise T, Ohmori K (2000) Protective effect of erdosteine against hypochlorous acid-induced acute lung injury and lipopolysaccharide-induced neutrophilic lung inflammation in mice. J Pharm Pharmacol 52:1411–1416PubMedCrossRefGoogle Scholar
  22. 22.
    Kavutcu M., Canbolat O., Ozturk S., Olcay E., Ulutepe S., Ekinci C., Gokhun I.H., Durak I (1996). Reduced enzymatic antioxidant defense mechanism in kidney tissues from gentamicin-treated guinea pigs: effects of vitamins E and C. Nephron 72: 269–274PubMedCrossRefGoogle Scholar
  23. 23.
    Rajeswari A, Varalakshmi P (2006) Low molecular weight heparin protection against oxalate-induced oxidative renal insult. Clin Chim Acta 370:108–114PubMedCrossRefGoogle Scholar
  24. 24.
    Fadillioglu E, Yilmaz HR, Erdogan H, Sogut S (2003) The activities of tissue xanthine oxidase and adenosine deaminase and the levels of hydroxyproline and nitric oxide in rat hearts subjected to doxorubicin: protective effect of erdosteine. Toxicology 191:153–158PubMedCrossRefGoogle Scholar
  25. 25.
    Parlakpinar H, Tasdemir S, Polat A, Bay-Karabulut A, Vardi N, Ucar M, Acet A (2005) Protective role of caffeic acid phenethyl ester (cape) on gentamicin-induced acute renal toxicity in rats. Toxicology 207:169–177PubMedCrossRefGoogle Scholar
  26. 26.
    Lora-Michiels M, Anzola K, Amaya G, Solano M (2001) Quantitative and qualitative scintigraphic measurement of renal function in dogs exposed to toxic doses of Gentamicin. Vet Radiol Ultrasound 42:553–561PubMedCrossRefGoogle Scholar
  27. 27.
    Bingham JB, Maisey MN, Joyce MR, Saxton HM (1978) Use of 99Tcm-DMSA as a static renal imaging agent. Contrib Nephrol 11:95–99PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2007

Authors and Affiliations

  • Mehmet Cabuk
    • 1
  • Ahmet Gurel
    • 2
  • Feyza Sen
    • 1
  • Nejat Demircan
    • 3
  1. 1.Department of Nuclear Medicine, Faculty of MedicineZonguldak Karaelmas UniversityZonguldakTurkey
  2. 2.Departments of Biochemistry, Faculty of MedicineZonguldak Karaelmas UniversityZonguldakTurkey
  3. 3.Department of Family Medicine, Faculty of MedicineZonguldak Karaelmas UniversityZonguldakTurkey

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