title: Long-term treatment with a beta-blocker timolol attenuates renal-damage in diabetic rats via enhancing kidney antioxidant-defense system.
abstract: 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.
authors.affiliation: Department of Histology-Embryology, Faculty of Medicine, Yildirim Beyazit University, Ankara, Turkey.
authors.forename: Hilal
authors.initials: H
authors.lastname: Gokturk
authors.forename: N Nuray
authors.initials: NN
authors.lastname: Ulusu
authors.forename: Muslum
authors.initials: M
authors.lastname: Gok
authors.forename: Erkan
authors.initials: E
authors.lastname: Tuncay
authors.forename: Belgin
authors.initials: B
authors.lastname: Can
authors.forename: Belma
authors.initials: B
authors.lastname: Turan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D013311:Streptozocin; D013999:Timolol / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D007004:Hypoglycemic Agents; D013311:Streptozocin; D013999:Timolol; D005954:Glucosephosphate Dehydrogenase; D005980:Glutathione Reductase; D005982:Glutathione Transferase