| Objectives: Grape procyanidins(GPC) are natural polyphenols extracted from grapes. It was reported that GPC has a lot of bioactivities such as antioxidation, antiradical, antitumor, and cardioprotective effect. In this study we investigated whether GPC can provide protection to lipid peroxidation in vitro and in vivo and study the mechanisms.Methods: 1. In vitro it takes as a model of oxidative damage in erythrocyte membrane induced by hydroxyl free radical which was produced by Fenton reaction.The antioxidative and protective effects of GPC on biomembranes were observed. Membrane fluidity was measured by the method of fluorescence polarization, and malanyldiadehyde(MDA),superoxide dismutase (SOD) by biochemical methods.2. Mice of 30-35 g were given adriamycin (ADR, i.p.) and the model of adriamycin-induced myocardial injury was used. Positive group received adriamycin alone. Three experimental groups received GPC 10 mg/kg, 100mg/kg or 200 mg/kg, o.p., before treating mice with adriamycin. The animals of control group received 7 days o.p. injections of saline. The activity of adenosine-5'-triphosphatase(ATPase) of myocardial mitochondria and myocardial enzyme CK activity in serum and specific antioxidant enzymes such as SOD and GSH-Px of myocardium were assayed. The content of MDA was also tested.3. Using the electron spin resonance (ESR) and spin trapping technique, the scavenging effects of different concentrations of GPC on active oxygen free radicals were studied, in which hydroxyl radical produced from Fenton Reaction and superoxide anion radical generated from irradiated riboflavin and lipid peroxyl radical generated from peroxidizing mitochondria system were taken as a model. The clearing effects of different concentrations of GPC on hydroxyl radical (.OH)and superoxygen anion(O)free radicals were also studied with Chemiluminescence method (CL). Results: 1. hydroxyl free radical increased the content of MDA, decreased membrane fluidity and activities of SOD, which indicate erythrocyte membranes were damaged by oxidation and caused lipid peroxidation. But GPC decreased the content of MDA remarkly, and improved the membrane fluidity significantly,and inhibited lipid peroxidation. 2. Adriamycin (ADR) induced severe myocardial damage, increased myocardial MDA content and myocardial enzyme CK activity in serum, decreased the activities of myocardial SOD and GSH-Px , induced the loss of adenosine-5'-triphosphatase(ATPase) activity of myocardial mitochondria in mice. Administration of GPC reduced significantly the cardiotoxicity induced by adriamycin and increased the total antioxidant capability(T-AOC). The activities of SOD and GSH-Px were also increased.3. Using the electron spin resonance (ESR) and spin trapping technique, GPC had dose-dependent scavenging effects on active oxygen species, the IC50 of GPC on hydroxyl radical and superoxide anion and lipid peroxyl radical being 128.9mg/L,89.4 mg/L,10.4 mg/L. In chemiluminescence system of hydroxyl radical and superoxygen anion, the IC50 value of GPC on .OH and O is 193.1mg/L and 33.0mg/L, respectively. It was suggested that GPC can scavenge hydroxyl radical and superoxide anion radical and lipid peroxyl radical in different degrees, in which the scavenging activity could be arranged in the following order : LOO. > O > . OH.Conclusion : 1. GPC can decrease the formation of MDA and inhibit lipid peroxidation in biomembrane damage induced by hydroxyl radical. In vivo GPC can increase of specific activity of antioxidant enzymes and protect the adenosine-5'-triphosphatase(ATPase) activity of mitochondria and inhibit lipid peroxidation. It was suggested that GPC has a good protective effect against lipid peroxidation induced by hydroxyl free radical in membrane and by adriamycin in myocardium.2. GPC has the scavenging activities on hydroxyl radical and superoxide anion radical and lipid peroxyl radical in different degrees. It was indicated that the protective effects of GPC against lipid p... |
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