Molecular and Cellular Biochemistry

, Volume 395, Issue 1–2, pp 177–186 | Cite as

Long-term treatment with a beta-blocker timolol attenuates renal-damage in diabetic rats via enhancing kidney antioxidant-defense system

  • Hilal Gokturk
  • N. Nuray Ulusu
  • Muslum Gok
  • Erkan Tuncay
  • Belgin Can
  • Belma Turan


The factors with increasing diabetes-prevalence lead to significant global increases in chronic kidney disease. Since hyperglycemia generates more ROS and attenuates cellular antioxidant-defense mechanisms, numerous studies demonstrated that hyperglycemia-induced oxidative stress played a major role in the extracellular matrix expansion in tissues. Although no direct relation between activation of beta-adrenergic (β-AR) system and kidney disease in diabetes and since β-blockers demonstrate marked beneficial effects due to their scavenging free radicals and/or acting as an antioxidant in diabetic animal studies, the eventual objective of the present study was to determine whether timolol-treatment of streptozotocin-induced diabetic rats (5 mg/kg, daily following diabetes-induction, for 12-week) has advantage to prevent hyperglycemia-induced renal-damage via enhancing the depressed antioxidant defense in the kidney. Light microscopy data and their quantification demonstrated that timolol-treatment prevented basically glomerular hypertrophy, expansion in mesangium cell size, thickening and fibrosis in glomerular basement membrane, and accumulation of glycogen into tubular epithelial cells. Additionally, electron microscopy data demonstrated that timolol-treatment could also prevent diabetes-induced changes in the kidney tissue such as hypertrophy in podocytes, lost of filtration gaps and slit-diaphragms, and vacuolization in the distal tubular cells. Biochemical analysis basically on enzymes of antioxidant-defense system, including glutathione-S-transferase, glutathione reductase, and glucose-6-phosphate dehydrogenase, further supported that diabetes-induced damage in the kidney is mostly dependent on the increased oxidative stress and timolol, having an antioxidant-like action, could protect the kidney against hyperglycemia-induced damage without normalization of high-blood glucose level. Consequently, it can be suggested that although β-blockers are widely used for the treatment of cardiovascular diseases, β-blocker therapy of diabetics seems to be a new therapeutic approach against hyperglycemia-induced kidney damage in diabetic patients.


Diabetes Antioxidants Beta-blockers Kidney 



This work has been supported partially by grant from TUBITAK SBAG-111S042.

Conflicts of interest

No potential conflicts of interest relevant to this article were reported.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Hilal Gokturk
    • 1
  • N. Nuray Ulusu
    • 2
  • Muslum Gok
    • 3
  • Erkan Tuncay
    • 4
  • Belgin Can
    • 5
  • Belma Turan
    • 4
  1. 1.Department of Histology-Embryology, Faculty of MedicineYildirim Beyazit UniversityAnkaraTurkey
  2. 2.Department of Biochemistry, School of MedicineKoc UniversityIstanbulTurkey
  3. 3.Departments of Medical Biochemistry, Faculty of MedicineHacettepe UniversityAnkaraTurkey
  4. 4.Department of Biophysics, Faculty of MedicineAnkara UniversityAnkaraTurkey
  5. 5.Department of Histology-Embryology, Faculty of MedicineAnkara UniversityAnkaraTurkey

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