[Sulfated polysaccharides as inhibitors of receptor activity of P-selectin and P-selectin-dependent inflammation]
Semenov AV. Mazurov AV. Preobrazhenskaia ME. Ushakova NA. Mikhailov VI. Berman AE. Usov AI. Nifant'ev NE. Bovin NV.
Institute of Experimental Cardiology, Cardiology Research Center, Moscow.
The inhibitory effects of sulfated polysaccharides-fucoidan and heparin on P-selectin-ligand interaction in vitro and on the ability of fucoidan to inhibit the leukocyte extravasation in rat peritonitis were studied. The lectin activity of P-selectin in vitro was based on its ability to bind lectin-labeled synthetic ligand, Sialyl-Lea/x, conjugated with polyacrylamide (PAA). Fucoidan and heparin inhibited binding of labeled ligand to both purified P-selectin and the activated platelets expressing P-selectin on their surface. The inhibitory effect of fucoidan 100-fold higher than that of heparin. As P-selectin plays an important role at an earlier stage of the inflammation process, the antiinflammatory action of fucoidan on P-selectin-dependent peritonitis in rats was studied. Peritonitis was induced by intraperitoneal injection of the peptone solution and was characterized by an increase in total cell number and neutrophil percentage in rat peritone exudate. Intravenous injection of fucoidan was found to cause a dose- and time-dependent reduction of neutrophil extravasation into inflamed peritoneum. The minimal dose of fucoidan, that was able to produce 96.8 +/- 2.9% inhibition of neutrophil extravasation--if administered within the first 15 min after peptone-B was 0.8 mg per rat. Significant effect of fucoidan injection (about 80% inhibition) was also obtained 1.5 h after the induction of inflammation. Fucoidan administered 2.5 h after peptone had virtually no effect on neutrophil extravasation. The data obtained show that fucoidan blocks the inflammation process at its earlier stages--most probably at the expense of its interaction with P-selectin.
[Dual reciprocal regulation of the succinate oxidation system in heart and liver mitochondria in pathological conditions]
Saakian IR. Saakian AG.
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region, Russia.
The phenomenon of the dual reciprocal regulation of succinate dependent 2H+/Ca2+ exchange was studied in heart and liver mitochondria of experimental animals (allogenic heart transplantation in rat; myocardium infarction in rabbits; pulmonary arteria coarctation in dogs) and in liver bioptates from patients with stomach ulcer. Under pathology two coupled but opposite changes (simultaneous activation and inhibition) in succinate dependent Ca2+ transport occur. The inhibition of Ca2+ transport was detected by its elimination with glutamate, being mostly pronounced after cycle of ADP phosphorylation added to suspension of mitochondria. The treatment of animal with 2-oxoglutarate abolished this inhibition. This was not observed in healthy animals. The described phenomenon can prevent hyperactivation of succinate oxidation under strong pathological (distress) influences.
[The measuring of blood plasma antioxidant activity by the hemoglobin-hydrogen peroxide-luminol system]
Teselkin IuO. Babenkova IV. Liubitskii OB. Klebanov GI. Vladimirov IuA.
Department of Biophysics, Russian State Medical University, Moscow, Russia.
The method of valuation of the blood plasma antioxidant activity (AOA) by the hemoglobin-hydrogen peroxide-luminol chemiluminescence system has been proposed. The method is based on the measuring the induction time of chemiluminescence that is directly proportional to the added volume of plasma or concentration of standard antioxidant. The ascorbate was taken as a standard. Blood plasma AOA has been expressed through the concentration of equivalent ascorbate solution (ascorbate equivalent). The influence of hemolysis and storage conditions of plasma on its detected AOA was investigated. The change of human blood plasma AOA after single administration of 2 g the ascorbate and its dynamics in patients with acute pancreatitis was studied.