The anti-ulcerogenic and anti-oxidant effects of various flavonoids have been frequently reported. We investigated the cytoprotective properties of quercetin, a natural flavone, in gastric mucosal injury induced by 50% ethanol, since in this experimental model the patho genesis of the lesions has been related with production of reactive oxygen species. The in volvement of neutrophil infiltration and the capacity of this flavonoid to restrain the oxida tive process produced in the gastric tissue after ethanol administration were also investigated. Oral pretreatment with the highest dose of quercetin (200 mg/kg), 120 min before absolute ethanol was the most effective anti-ulcer treatment. Thiobarbituric acid reactive substances in the gastric mucosa, an index of lipid peroxidation, were increased by ethanol injury, but the increase was inhibited by the administration of 200 mg/kg of quercetin. This dose also induced a significant enhancement in the levels of mucosal non-protein SH compounds (im portant anti-oxidant agents) and in glutathione peroxidase activity. Exposure of the gastric mucosa to 50% ethanol induced a significant increase in myeloperoxidase activity, an index of neutrophil infiltration. Flowever, quercetin was not able to modify the increase in enzy matic activity generated by the necrotizing agent. The activity of superoxide dismutase en zyme involved in several antioxidant processes was also not significantly modified after quer cetin treatment.These results suggest that the anti-ulcer activity of quercetin in this experimental model could be partly explained by the inhibition of lipid peroxidation, through decrease of reactive oxygen metabolites. However, the inhibition of neutrophil infiltration or the increase of su peroxide dismutase activity does not appear to be involved in gastroprotective effect of this flavonoid.

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In human beings, melatonin is secreted in a cyclic way by the pineal gland, although it has been detected in other tissues. Synthesis of melatonin takes place in the pinealocyte. It depends on adrenergic stimulation, and its secretion is related to the photoperiod in a circadian model of low activity during light phase and high activity at night time. Former studies aimed to establish the mechanisms by which melatonin carries out its biological function, proved the existance of high affinity binding sites. However, melatonin can pass through the plasmatic membrane; this property suggested a possible activity of the hormone inside the cell trough activation of nuclear receptors. Moreover, melatonin can act by itself as a potent oxygen-free-radical scavenger, which renders it a very strong antioxidant. It is currently accepted that melatonin plays an important role in numerous physiological processes. The gastrointestinal tract of numerous animal species contains melatonin, which is synthesized essentially by intestinal enterochrommaffin cells. Some investigations have revealed that its liberation follows also a circadian rhythm, although its secretion pattern might be influenced by nutritional factors. Receptors for melatonin have been identified in the digestive system, therefore the indolamine might play a leading role in different aspects of the vast digestive physiopathology. The hormone may interact with receptors and subsequently stimulate the synthesis of gastroprotective hormones and also exerts a direct defense on the epithelium, enhances submucosal blood flow and prevents the damage induced by ischemia followed by reperfusion. Moreover, studies have shown that treatment with melatonin reduces the severity of the lesions induced by NSAIDs on gastric mucosa suggesting a beneficial role of melatonin in preventing this gastropathy related to antiinflammatories.

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An endocytic vesicle is formed from a flat plasma membrane patch by a sequential process of invagination, bud formation and fission. The scission step requires the formation of a tubular membrane neck (the fission pore) that connects the endocytic vesicle with the plasma membrane. Progress in vesicle fission can be measured by the formation and closure of the fission pore. Live-cell imaging and sensitive biophysical measurements have provided various glimpses into the structure and behaviour of the fission pore. In the present study, the role of non-muscle myosin II (NM-2) in vesicle fission was tested by analyzing the kinetics of the fission pore with perforated-patch clamp capacitance measurements to detect single vesicle endocytosis with millisecond time resolution in peritoneal mast cells. Blebbistatin, a specific inhibitor of NM-2, dramatically increased the duration of the fission pore and also prevented closure during large endocytic events. Using the fluorescent markers FM1-43 and pHrodo Green dextran, we found that NM-2 inhibition greatly arrested vesicle fission in a late phase of the scission event when the pore reached a final diameter of ∼ 5 nm. Our results indicate that loss of the ATPase activity of myosin II drastically reduces the efficiency of membrane scission by making vesicle closure incomplete and suggest that NM-2 might be especially relevant in vesicle fission during compound endocytosis.