ABSTRACT
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.
Subject(s)
Cardiomyopathies/drug therapy , Diabetes Mellitus, Experimental/complications , Flavonoids/pharmacology , Ventricular Function, Left/drug effects , Animals , Blood Glucose , Cardiomyopathies/etiology , Hemodynamics , Lipid Peroxidation , Male , Membrane Glycoproteins/metabolism , NADPH Oxidase 2 , NADPH Oxidases/metabolism , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type III/metabolism , Oxidative Stress , Plant Extracts , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Streptozocin , Thiobarbituric Acid Reactive Substances/metabolism , Tubulin/metabolismABSTRACT
Reactive oxygen species (ROS) are key factors playing important roles in tissue damage of airways under different pathological conditions. Effects of ROS (superoxide anion, H2O2 and hydroxyl radical) were recorded on isometric tension of intact and epithelium denuded, not precontracted guinea pig trachea. Superoxide anion was produced by xanthine/xanthine oxidase and hydroxyl radical either by FeSO4/H2O2 or FeSO4/ascorbic acid. In intact preparations, the muscle tension was unaffected by superoxide anion, while H2O2 and hydroxyl radical produced a biphasic response, contraction followed by relaxation. Both the amplitude and duration of contractions evoked by H2O2 were larger than those caused by hydroxyl radical producing systems. On denuded tracheal strips, superoxide anion elicited also a biphasic response, and the H2O2 and hydroxyl radical produced contractions were of higher amplitude and of longer duration than in intact tissues. Indomethacin pretreatment enhanced or slightly reduced the amplitude of contractions evoked by both H2O2 and hydroxyl radical on the intact and denuded preparations, respectively. Moreover, the duration of contractions of the trachea induced by oxidative systems was prolonged. Indomethacin did not affect the action of superoxide anion on the intact tissues and reduced the amplitude of the biphasic response on denuded ones. Nordihydroguaiaretic acid pretreatment did not alter the responses elicited by ROS in intact preparations and reduced their action on the denuded ones. Our results suggest that a) various ROS contract tracheal smooth muscle with simultaneous release of epithelium derived relaxing factors, b) epithelium possesses superoxide anion scavenging capacity which is high enough to protect smooth muscle from its actions, and c) cyclooxygenase products participate in relaxation and lipoxygenase products in contraction caused by ROS in the guinea pig trachea.
