Toshiki Takemura

Role of oxygen-derived free radicals in the pathogenesis of gastric mucosal lesions in rats.

The role of oxygen-derived free radicals and lipid peroxidation in the pathogenesis of acute gastric mucosal erosion was investigated in rat models produced by burn shock stress, by treatment with regional hyperthermia, platelet activating factor, and compound 48/80, and by ischemia-reperfusion. In all experimental models, the increase in the gastric erosions and in TBA reactants in the gastric mucosa were significantly inhibited by the treatment with superoxide dismutase (SOD) and/or catalase. Pretreatment with allopurinol, a competitive inhibitor of xanthine oxidase, prevented considerably the gastric injury (a) induced by burn shock, (b) produced by treatment with compound 48/80, and (c) caused by ischemia-reperfusion. By the treatment with anti-rat neutrophil antibody, the gastric mucosal injuries induced by regional hyperthermia, platelet activating factor, and compound 48/80 were significantly inhibited; however, burn shock and ischemia-reperfusion injuries were not inhibited. These results suggest that oxygen-free radical and lipid peroxidation contribute to the formation of gastric mucosal lesions, and that the sources of oxygen radicals seem to be different among these experimental models.

Scavenging Effects of Aspalathus Linealis (Rooibos Tea) on Active Oxygen Species

Rooibos tea ia a totally unique South African product of the plantAspalathus linealis which is only produced in the Cadarberg mountains around Clanwilliam. In South Africa it is mainly used as a substitute for the Oriental black tea by people who enjoy it either hot or cold, or by those who regard it as a healthy drink. Clinically, Rooibos tea is often prescribed for nervous tension, allergies, stomach and digestive problems. For evaluation of its antioxidant action, reactivity of Aspalathus linealis, ascorbic acid, and quercetin which is one of non-glycosidically linked flavonoids included in Asparathus linealis, to various reactive oxygen species were assessed by electron spin resonance (ESR) sipectrometry using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trapper1,2.

Protection by Seleno-Organic Compound, Ebselen, Against Acute Gastric Mucosal Injury Induced by Ischemia-Reperfusion in Rats

Several pathogenetic mechanisms have been suggested to account for acute gastric mucosal injury. Recently, Oxigen-derived free radicals and lipid peroxidation have been suggested to play a role in the pathogenesis of gastric mucosal injury1,2,3). Ischemia and reperfusion are of the greatest importance in the pathology of many diseases. There has been great interest in the possible role of oxygen radical species in ischemia-reperfusion in the gastric mucosa4). A synthetic seleno-organic compound, 2-phenyl-1, 2 benzoisoselenazol-3(2H)-one(Ebselen), shows a glutathione peroxidase(GSHPx)-like activity-5,6). This study was designed to examine the protective effects of the agent, Ebselen against the gastric mucosal injury induced by ischemia-reperfusion.

Pathogenesis of platelet-activating factor-induced gastric mucosal damage in rats.

Platelet-activating factor (PAF), given intravenously, induced erosions and hyperemia to the rats stomachs. Gastric mucosal blood flow was decreased and thiobarbituric acid (TBA) reactants (an index of lipid peroxidation) in the gastric mucosa were increased 10 min after PAF injection. Superoxide dismutase plus catalase reduced the gastric mucosal lesions and TBA reactants, but had no influence on gastric mucosal blood flow. A reduction in the number of circulating polymorphonuclear leukocytes (PMN) reduced the gastric mucosal damage and TBA reactants, and inhibited the decrease in gastric mucosal blood flow, as observed 30 and 60 min after PAF injection. PAF induced superoxide production by rat PMN and enhanced that stimulated by opsonized zymosan or phorbol myristate acetate. These results suggest that microcirculatory disturbance and oxygen-derived free radicals generated by PMN play important roles in gastric mucosal lesions induced by PAF.

Antioxidative Action of Zinc-Carnosine Compound Z-103

The objective of the present study was to examine the anti-free radical action of Z-103 in vitro. Z-103 is a novel synthetic compound of zinc and carnosine (β-alanyl-L-histidine) which has strong anti-ulcer action in many types of animal models.1Free radicals have come to considered to be playing a role in the pathogenesis of gastric mucosal injuries2,3. The antifree radical action of Z-103 were expected because zinc and carnosine have antioxidative properties4,5. To know its anti-free radical action in vitro will be significant to understand its mechanism of action as anti-ulcer drug.

Role of Xanthine-Xanthine Oxidase Systems and Polymorphonuclear Leukocytes in Lipid Peroxidation in Compound 48/80-Induced Gastric Mucosal Injury in Rats

Recent studies have demonstrated that active oxygen species and lipid peroxidation might be involved in the formation of gastric mucosal lesions1–3. Compound 48/80 is a mast cell degranulator to release histamine and serotonin. Repeated administration of a small dose of this agent can induce gastric mucosal injury in rats with a low mortality rate4. This study was designed to evaluate a role of active oxygen species and lipid peroxidation in the pathogenesis of gastric mucosal injury induced by compound 48/80 in rats. Fur- thermore, the role of xanthine-xanthine oxidase systems and polymorphonuclear leukocytes (PMN) for the source of active oxygen species was examined.

Zinc-Carnosine Chelate Compound (Z-103) Attenuates Acute Gastric Mucosal Injury Induced by Ischemia-Reperfusion in Rats

A novel synthesized agent, zinc N-(3-aminopropionyl)-L-histidine (Z-103, Fig. 1), is a chelate compound that consists of zinc iron and L-carnosine. Carnosine was discovered in 1900 by Gulewitsch and Amiradzibi1 from meat extract, and is reportedly present in the range of 1–20 mM in the skeletal muscle and brain of many animals and humans2. Recently, several reports have described the antioxidative activity of carnosine, such as efficient singlet oxygen scavengers3, peroxy radical scavengers4, efficient chelating agent for copper and other transitional metals4, and Superoxide scavenging activity in the presence of copper or zinc5.

Role of Lipid Peroxidation and Oxygen Radicals in Compound 48/80-Induced Gastric Mucosal Injury in Rats

Repeated administration of a small dose of compound 48/80 induced acute gastric mucosal injury in rats. Thiobarbituric acid (TBA) reactants in the gastric mucosa were significantly increased and serum alpha-tocopherol was significantly decreased after the treatment. The total area of gastric lesions and the increase in TBA reactants in the gastric mucosa were significantly reduced by pretreatment with superoxide dismutase (SOD) and/or catalase, allopurinol and anti-rat polymorphonuclear leukocytes (PMN) antibody. Lipid peroxidation and oxygen radicals derived from both the xanthine-xanthine oxidase system and PMN may be involved in the pathogenesis of compound 48/80-induced gastric mucosal injury.

Role of lipid peroxidation and free radical scavengers on endotoxin shock

Abstract Experimental shock was induced by a single intravenous injection of 100 mg/kg of endotoxin. After the injection of endotoxin, systolic blood pressure was reduced and heart rate was increased. The activities of serum lysosomal enzymes, such as acid phosphatase and β-glucuronidase, were increased. Serum thiobarbituric acid-reactive substances, which are important and damaging products of free radical lipid peroxidation, were significantly increased, and the serum α-tocopherol/cholesterol ratio was significantly decreased. These findings suggest that lipid peroxidation and vitamin E may play an important role in these pathological conditions.

Role of Free Radical Lipid Peroxidation in Burn and Endotoxin Shock

Enhanced free radical generation leading to lipid peroxidation has been claimed to be associated with various disorders (Bulkey, 1983). There is considerable indirect evidence supporting a role for oxygen radicals in circulatory shock. Crowell et al. (1969) and Cunningham and Keaveny (1978) reported that allopurinol, a competitive inhibitor of xanthine oxidase, substantially increased the survival rate of dogs subjected to hemorrhagic shock. Severe burns result in both local and systemic hemodynamic changes (Gilmore and Handford, 1956; Wolfe and Miller, 1976; Adams et al., 1981), as well as in endocrine (Turinsky et al., 1977), neuroendocrine (Cova and Glaviano, 1968; Goodall and Moncrief, 1965), and metabolic (Robinson and Miller, 1981; Wolfe et al., 1977) alterations. Acute endotoxin shock is rapidly produced with Escherichia coli endotoxin (Balis et al., 1978).