Carvedilol and antioxidant proteins in a type I diabetes animal model.
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.


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.
CNC - Center for Neuroscience and Cell Biology, Biocant Park, University of Coimbra, Cantanhede, Portugal.
Cátia V
CV
Diogo
CNC - Center for Neuroscience and Cell Biology, Biocant Park, University of Coimbra, Cantanhede, Portugal.|Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
Cláudia M
CM
Deus
Nencki Institute of Experimental Biology, Department of Biochemistry, Polish Academy of Sciences, Warsaw, Poland.
Magdalena
M
Lebiedzinska-Arciszewska
Nencki Institute of Experimental Biology, Department of Biochemistry, Polish Academy of Sciences, Warsaw, Poland.
Aleksandra
A
Wojtala
Nencki Institute of Experimental Biology, Department of Biochemistry, Polish Academy of Sciences, Warsaw, Poland.
Mariusz R
MR
Wieckowski
CNC - Center for Neuroscience and Cell Biology, Biocant Park, University of Coimbra, Cantanhede, Portugal.
Paulo J
PJ
Oliveira
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants; D001786:Blood Glucose / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D000072105:Superoxide Dismutase-1 / Q000187:drug effects / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D000319:Adrenergic beta-Antagonists; D000975:Antioxidants; D001786:Blood Glucose; D002227:Carbazoles; D000077261:Carvedilol; D053148:Caspase 3; D002374:Catalase; D011412:Propanolamines; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606292:Sod1 protein, rat; C505410:Casp3 protein, rat
Carvedilol; hyperglycaemia; mitochondria; oxidative stress; streptozotocin