Jorge Suárez

Day-night cycle of lipid peroxidation in rat cerebral cortex and their relationship to the glutathione cycle and superoxide dismutase activity

Lipoperoxidation, glutathione cycle components and superoxide dismutase activity show a day-night rhythm in the cerebral cortex of the rat. The highest lipoperoxidative activity is observed during the night (20.00-04.00 h). The enhancement in lipoperoxidation occurs concurrently with a decrease in glutathione peroxidase activity, an increase in superoxide dismutase activity and an increase in the double bonds in the brain cortex lipid fraction. The changes described in this paper seem to be related to a succession of light and dark periods, or to fasting and feeding periods. We propose that those fluctuations could act as a physiological oscillator with an important role in modulating the membrane properties of the nerve cell.

Circadian variations of adenosine level in blood and liver and its possible physiological significance

The role of adenosine as a possible physiological modulator was explored by measuring its concentration in different tissues during a 24-hour period. Initially the circadian variations of adenosine and other purine compounds such as inosine, hypoxanthine, uric acid and adenine nucleotides were studied in the rat blood. A daily cyclic response was observed, with low levels of adenosine from 08.00 - 20.00 h, followed by an increase from this time on. Inosine and hypoxanthine levels were elevated during the day and low at night. The uric acid changes observed indicate that the decrease in purine catabolism coincides with a decrease in inosine and hypoxanthine levels and an increase in adenosine. The blood adenine nucleotides, energy charge and phosphorylation potential remained constant during the day and showed oscillatory changes during the night. Similar studies were made in the liver, a primary source of circulating purines. Liver adenosine was high during the night while inosine and hypoxanthine remained low along the 24 hours. The results suggest that liver purine metabolism might participate in the maintenance and renewal of the blood purine pool and in the energy state of erythrocytes in vivo.

Day-night cycle of lipidic composition in rat cerebral cortex

A study of the lipidic pattern of the cerebral cortex of the normal adult rat during the daynight cycle was carried out. The changes observed were the following: phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine plus phosphatidic acid showed a peak at 16:00 hr possibly due to a general increase in phospholipid biosynthesis. During the nocturanl period the variations of phosphatidylcholine and phosphatidylethanolamine were not clearly observe, they might be due to an increase in the interconversion or exchange reaction, since the ratio phosphatidylcholine/phosphatidylethanolamine showed a significative change at 04:00 hr. This occurred because small but opposite changes in both phospholipids were observed, suggesting an increase in the methylation reactions of phospholipids. Cardiolipin showed a significant peak at 04:00 hr. Plasmalogens exhibited significative changes, an important diminution at 16:00 hr and a prominent peak at 24:00 hr. Cholesterol levels were high during the light period and low in the dark one. Cerebrosides and gangliosides showed no day-night variations. The changes observed indicate a phenomenon of biological rhythmicity synchronized by the photoperiod, suggesting that these fluctuations could act as physiological modulators of the properties and functions of the nerve cell membrane.

Inhibition of S-Adenosyl-L-homocysteine hydrolase by adrenaline in isolated Guinea-pig papillary muscles

Purified S-adenosyl-L-homocysteine hydrolase from Dictyostelium discoideum or rabbit erythrocytes is inactivated when incubated with cAMP. The aim of this study was to investigate whether adrenaline, which increases cytosolic cAMP and calcium concentrations, is able to modify in situ the activity of S-adenosyl-L-homocysteine hydrolase in the heart. The enzyme was assayed in a crude extract obtained from superfused guinea-pig papillary muscles with the different tested substances. Adrenaline was found to inhibit S-adenosyl-L-homocysteine hydrolase in papillary muscles in a concentration-dependent fashion. This inhibition was associated with an increase in the concentration of S-adenosyl-L-homocysteine (326%), and a decrease of adenosine (40%). beta-Adrenoceptors are involved in the effect of adrenaline, since isoproterenol, a beta-adrenergic agonist, inhibited the enzyme, whereas the beta-adrenergic blocker, propranolol, prevented this inhibition. Participation of calcium in the inhibitory effect of adrenaline was suggested because the calcium channel blocker, verapamil, suppressed this inhibition, and high calcium in the perfusion medium inhibited the enzyme. In vitro experiments with calcium were performed in a semi-purified fraction of the enzyme, resulting in a concentration-dependent inhibition of the enzyme. Calcium concentration, which inhibited the enzyme 50%, was in the millimolar range for control and in the micromolar range for the obtained enzyme from adrenaline-treated muscles, indicating a different sensitivity to calcium inhibition. We conclude that adrenaline inhibits S-adenosyl-L-homocysteine hydrolase in situ, probably by a calcium-modulated mechanism.

Effect of adenosine on the serum levels of glucose, insulin and glucagon In vivo

The in vivo effect of adenosine on the serum levels of glucose, insulin and glucagon in rats fasted for twenty four hours or after an oral glucose load were studied. Under fasting conditions adenosine produced an hyperglycaemia without change in the insulin or glucagon serum levels. After a glucose load adenosine induced a marked hyperglycaemia concomitant to a decrease in insulin serum levels and an increase in glucagon serum levels. Adenosine did not alter the relationship between insulin and glucagon. In vivo adenosine administration altered the secretion of hormones by the islets of Langerhans (increased the release of glucagon and decreased the secretion of insulin) but this was only clearly observable under stimulated conditions. Adenosine did not alter the regulatory mechanism(s) that modulate the relationship between insulin and glucagon.

Role of Nitric Oxide in Isoproterenol-Induced Myocardial Infarction

Myocardial infarction (MI) is an important cause of mortality around the world, resulting from an ischemic necrosis induced by a vascular occlusion. In general, MI occurs unexpectedly and the clinical syndrome previous to MI is difficult to detect. Animal models of MI are very useful in the study of prevention, diagnosis and therapy design for human MI [Smith & Nuttall., 1985]. MI induced by ligation of the left anterior descending coronary artery is the animal model most frequently used; however, the anesthesia and surgical procedures affect the conditions in which the infarction occurred [Wang et al., 2006]. Therefore, MI in animal models studies should be induced in conscious animals with intact reflexes for greater clinical relevance. Myocardial infarction induced by isoproterenol (ISO) using toxic concentration of this β-adrenergic agonist drug, originally described by Rona [Rona et al., 1959] has been used by several groups to study the cardiotoxic effects of this molecule [Stanton et al,1969]. This model becomes relevant if we consider that increased adrenergic activation plays a role as a trigger of acute myocardial infarction. In addition, the stress associated to MI in patients, increases catecholamine blood levels, which in turn, augment contraction force of the heart and ATP utilization favoring an energetic unbalance [Wallace & Klein, 1969, Ueba et al, 1973].