Pycnogenol improves left ventricular function in streptozotocin-induced diabetic cardiomyopathy in rats.
We studied whether Pycnogenol (PYC) may attenuate the development of experimental streptozotocin-induced diabetic cardiomyopathy in rat. In addition, we aimed to study whether PYC affects cardiac oxidative stress and the protein expression of reactive oxygen species (ROS)-producing molecules (gp91(phox)-containing NADPH oxidase and NO-signalling proteins). Experimental diabetes mellitus was manifested by hyperglycaemia and impaired cardiac function estimated using left ventricular catheterisation in vivo. PYC lowered fasting plasma glucose and normalized basal cardiac function. Excessive oxidative stress in streptozotocin (STZ) hearts, evidenced by 40% increase (P < 0.05) of thiobarbituric acid reactive substances (TBARS) concentration, was associated with increased expression of gp91(phox) (by 75%, P < 0.05), iNOS (by 40%, P < 0.05) and alpha-tubulin (by 49%, P < 0.05), but unchanged expression of eNOS and its alosteric regulators, as compared to CON. PYC failed to affect these expression abnormalities. Our study shows that PYC corrects diabetic cardiac dysfunction, probably by its metabolic and direct radical scavenging activity without affecting the molecular maladaptations of ROS-producing enzymes and cytoskeletal components.
Klimas
Jan
J
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic. klimas@fpharm.uniba.sk
Kmecova
Jana
J
Jankyova
Stanislava
S
Yaghi
Diana
D
Priesolova
Elena
E
Kyselova
Zuzana
Z
Musil
Peter
P
Ochodnicky
Peter
P
Krenek
Peter
P
Kyselovic
Jan
J
Matyas
Stefan
S
D000818:Animals; D001786:Blood Glucose; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D005419:Flavonoids / Q000494:pharmacology*; D006439:Hemodynamics; D015227:Lipid Peroxidation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D010936:Plant Extracts; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects*
D001786:Blood Glucose; D005419:Flavonoids; D008562:Membrane Glycoproteins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D014404:Tubulin; C024070:pycnogenols; D013311:Streptozocin; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases