Carvedilol and antioxidant proteins in a type I diabetes animal model

Eur J Clin Invest. 2017 Jan;47(1):19-29. doi: 10.1111/eci.12696. Epub 2016 Nov 23.


Background: Patients with diabetes are at a high risk of developing both micro- and macrovascular disease. Hyperglycaemia seems to be the main factor in the pathogenesis of diabetic cardiomyopathy, often based on increased oxidative stress. Carvedilol, a β-adrenergic blocker, has intrinsic antioxidant properties and was previously described to be effective in the protection of cardiac mitochondria against oxidative stress. The objective of this study was to evaluate the effect of carvedilol on hyperglycaemia-induced oxidative damage and mitochondrial abnormalities in cardiac and skeletal muscle in streptozotocin-treated rats.

Materials and methods: Body mass, blood glucose, the level of protein carbonylation, caspase-9- and caspase-3-like activities, mitochondrial proteins, the status of antioxidant defence system and stress-related proteins were evaluated in streptozotocin vs streptozotocin + carvedilol (1 mg/kg/day)-treated rats.

Results: The results showed that carvedilol decreased blood glucose in streptozotocin-treated animals. Content of catalase in the heart and SOD2, SOD1 and catalase in skeletal muscle were increased by carvedilol treatment in streptozotocin-treated animals. At this particular time point, streptozotocin-induced hyperglycaemia did not cause caspase activation or increase in protein carbonylation status. The data showed that carvedilol increased the level of antioxidant enzymes, what may contribute to preserve cell redox balance during hyperglycaemia. We also showed here for the first time that carvedilol effects on streptozotocin-treated rats are tissue dependent, with a more predominant effect on skeletal muscle.

Conclusions: Based on data showing modulation of the antioxidant network in the heart, carvedilol may be beneficial in diabetic patients without advanced disease complications, delaying their progression.

Keywords: Carvedilol; hyperglycaemia; mitochondria; oxidative stress; streptozotocin.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Antioxidants
  • Blood Glucose / metabolism
  • Carbazoles / pharmacology*
  • Carvedilol
  • Caspase 3 / drug effects
  • Caspase 3 / metabolism
  • Catalase / drug effects
  • Catalase / metabolism
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Disease Models, Animal
  • Male
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism
  • Mitochondria, Muscle / drug effects*
  • Mitochondria, Muscle / metabolism
  • Oxidative Stress / drug effects*
  • Propanolamines / pharmacology*
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / drug effects
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1 / drug effects
  • Superoxide Dismutase-1 / metabolism


  • Adrenergic beta-Antagonists
  • Antioxidants
  • Blood Glucose
  • Carbazoles
  • Propanolamines
  • Carvedilol
  • Catalase
  • Sod1 protein, rat
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • superoxide dismutase 2
  • Casp3 protein, rat
  • Caspase 3