Biomedical subjects

R Curi

Publications and source records attributed to R Curi.

At least 145 records · Page 8Linked to original sources

PubMed1994

Metabolic changes in lymphoid organs as induced by fatty acids-rich diets during ageing.

Previous reports of our laboratory have shown that w-6 PUFA-rich diets (UC) given to rats during 6 weeks causes important changes of the metabolism of the lymphoid organs. In this study, the effect of saturated fatty acids-rich diet (SC) and also the persistence of the changes caused by (UC) were investigated during ageing (14 months). The major changes previously reported for UC fed rats, during 6 weeks, fully persisted when this feeding condition was maintained for 14 months. Moreover, the SC group also showed modifications of the activities of key enzymes of glucose and glutamine metabolism of the lymphoid organs with ageing. Both groups fed fatty acids-rich diets markedly reduced the rate of lipogenesis in the liver, spleen, and thymus in contrast to slight changes reported for 6 weeks. These results suggest that fatty acids-rich diets, by causing important metabolic alterations, may pronounce the impairment of the immune function observed during ageing.

Aging↗

PubMed1994

Antioxidant enzyme activities in the lymphoid organs and muscles of rats fed fatty acids-rich diets subjected to prolonged physical exercise-training.

Rats weighing 45-50 g were fed 3 diets for 8 wk: a balanced control diet (CD) consisting of 4% fat (polyunsaturated/saturated fatty acids [P/S] ratio 2.9/1) and two fat-rich diets: polyunsaturated (UD)--P/S 7.6/1 and saturated (SD) P/S 0.3/1. After 8 wk feeding on the respective diets, rats were subjected to swimming for 90 min at 30 degrees C daily, 5 d/wk for 8 wk. At the end of this period, the rats were killed and the lymphoid organs (LO--thymus, spleen, and mesenteric lymph nodes) and muscles (soleus and gastrocnemius) removed for the measurement of TBARs (Thiobarbituric Acid Reactant Substances) content and of the activities of antioxidant enzymes (CuZn- and Mn-Superoxide dismutase--SOD--, catalase, and glutathione peroxidase). To evaluate the changes in the sites of generation of reducing equivalents involved in the formation of free radicals, the activities of citrate synthase and glucose-6-phosphate dehydrogenase were measured. The exercise-training clearly modified the enzyme activities and TBARs content of the lymphoid organs and skeletal muscles, but this effect was dependent upon the diet given to the rats. However, fatty acid rich diets had presented a more pronounced effect on the studied aspects than did physical activity. Although one could expect a summatory effect of polyunsaturated fatty acid-rich diet and exercise-training, swimming increased the activities of CuZn- and Mn-SOD in almost all tissues from the elevated level promoted by fat-rich diets.

Animals↗

PubMed1994

Superoxide dismutase, catalase, and glutathione peroxidase activities in muscle and lymphoid organs of sedentary and exercise-trained rats.

The effect of swimming-training upon the activities of the enzymes involved in the generation of reducing-equivalents (citrate synthase-mitochondria and glucose-6-phosphate dehydrogenase-cytosol) and of antioxidant enzymes (CuZn- and Mn-SOD, catalase and glutathione peroxidase) in the lymphoid organs (thymus, mesenteric lymph nodes and spleen) was examined. The skeletal muscles (soleus-red and gastrocnemius-white) were also studied. Although our data suggest an apparently random, organ-specific change in enzymatic activity, some interesting trends can be observed. Firstly, the increased citrate synthase and Mn-SOD activities observed in red, but not in white muscle, corroborate the well-known effect of endurance exercise-training on mitochondrial oxidative metabolism. Secondly, there was an inverse relationship between TBARs-monitored lipoperoxidation and glutathione peroxidase activity in all tissues studied, what is in accordance with the previous findings showing that such enzyme exerts the fine control of intracellular lipoperoxide concentration. Except in the case of the spleen, there was a trend for elevated glucose-6-phosphate dehydrogenase activity, coadjuvant of glutathione peroxidase in the antioxidant response to physical exercise in all tissues. Thirdly, Mn-SOD and catalase were conspicuously associated to oxidative stress in the thymus, while glutathione and catalase could be linked to this parameter in the spleen. Fourthly, the lymph nodes seem to be more dependent on the glucose-6-phosphate dehydrogenase/glutathione peroxidase pair for protection against damage promoted by physical exercise. Mn-SOD and catalase activities were lower in the lymph nodes after swimming training.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Modulation of insulin secretion and 45Ca2+ efflux by dopamine in glucose-stimulated pancreatic islets.

1. The effect of dopamine on calcium efflux and insulin secretion is examined in the present study. For this purpose, islets isolated from adult Wistar rats were perfused or incubated at 37 degrees C for 60 min. 2. The results obtained from perfused islets indicate that 100 microM dopamine, in the presence of 5.6 mM glucose, increases insulin secretion and causes a modest elevation of 45Ca2+ efflux. However, glucose stimuli (from 5.6 to 16.7 mM) provoked an unexpected reduction of insulin release, with no alteration in calcium efflux, when 100 microM dopamine was present in the perfusion medium. 3. Similar findings were obtained in incubated islets when the prolonged effect of dopamine was investigated. 4. The observations described above led us to conclude that bioactive amines might play an important role in the modulation of the glucose-induced insulin secretion.

Animals↗

PubMed1994

The effect of propionate on lipid synthesis in rat lymphocytes.

1. The effect of propionate on lipid synthesis in lymphocytes cultured for 24 hr and incubated for 2 hr was investigated. 2. [1-14C]-propionate was incorporated mainly into phospholipids in both control and concanavalin A (Con A) stimulated cultured lymphocytes. 3. The content of free coenzyme A markedly decreased in 2 hr incubated lymphocytes when propionate was added to the medium at concentrations from 10 to 100 mmol/l. 4. Propionate at 40 mmol/l decreased the incorporation of [1-14C]-palmitate into phospholipids (86%), triacylglycerol (87%) and cholesterol ester (98%) and increased in cholesterol (133%) of cultured lymphocytes. 5. Addition of propionate into the culture medium at 2.5 and 5.0 mmol/l concentrations markedly increased the activity of hydrolases of various acylCoA derivatives. 6. The results suggest that propionate may reduce the content of acylCoA and so its esterification and this might be important for the regulation of lymphocytes proliferation.

Animals↗

PubMed1994

Metabolism of a chylomicron-like emulsion in rats with Walker 256 tumor: influence of a polyunsaturated (n-6) compared with a saturated fatty acid-rich diet.

OBJECTIVE: Defects in lipid metabolism secondary to development of cancer are frequently observed and, in experimental animals, manipulation of the lipid content of the diet can significantly influence tumor growth. The effects of a high polyunsaturated fat vs a high saturated fat diet upon the chylomicron metabolism of rats bearing Walker 256 tumor were examined. METHODS: Chylomicron-like emulsions labeled with radioactive lipids were injected into rats bearing the tumor and control rats. The two groups were previously given a high polyunsaturated (n-6) (15% fat) or a high saturated fat diet (15% fat) for 6 weeks. Following injection, plasma samples were collected at 8 time intervals in 60 minutes and tissue fragments were excised after the animals were killed, for determination of the plasma fractional clearance rate (FCR, min-1) and organ uptake of radioactive lipids. RESULTS: FCR of the emulsion triacylglycerols (TG) and cholesteryl oleate ether (CE) decreased in the tumor-bearing rats fed the polyunsaturated fat-rich diet (FCR-TG control = 0.26 +/- 0.09, tumor = 0.11 +/- 0.04; FCR-CE controls = 0.18 +/- 0.05, tumor = 0.10 +/- 0.02), as did activity of the lipoprotein and hepatic lipases (p < 0.05). This indicates that in this group, the presence of the tumor elicited defective lipolysis and delayed removal of the emulsion from the plasma. In the group fed the saturated fatty acid-rich diet, however, these alterations were not observed (FCR-TG control = 0.21 +/- 0.11, tumor = 0.20 +/- 0.08; FCR-CE control = 0.13 +/- 0.06, tumor = 0.10 +/- 0.05). The uptake by several tissues of the emulsion CE was similar in all rat groups. CONCLUSION: The saturated fat-rich diet avoids the deficiency in chylomicron lipolysis elicited by the implanted Walker 256 tumor.

Animals↗

PubMed1994

Control of superoxide dismutase, catalase and glutathione peroxidase activities in rat lymphoid organs by thyroid hormones.

This study examined the effect of experimental hyper- and hypothyroidism on the superoxide dismutase, catalase and glutathione peroxidase activities of rat lymphoid organs (mesenteric lymph nodes, spleen and thymus) and muscles (soleus and gastrocnemius-white portion) for comparison. The capacity for the generation of reducing equivalents was also investigated: activities of glucose-6-phosphate dehydrogenase (pentose-phosphate pathway) and citrate synthase (Krebs cycle). Hyperthyroidism tended to enhance lipid peroxide content in all tissues. This effect may result from (1) a high capacity for the generation of reducing equivalents in cytosol and mitochondria and (2) a reduced activity of catalase in the lymphoid organs and of glutathione peroxidase in the muscles. The process of lipid peroxidation in these tissues caused by hyperthyroidism was probably slowed down by the augmentation of CuZn- and Mn-superoxide dismutase (Mn-SOD) activities observed under this condition. Hypothyroidism tended to diminish lipid peroxidation and did not affect citrate synthase and glucose-6-phosphate dehydrogenase activities in the lymphoid organs and muscles. Low levels of thyroid hormones tended to diminish Mn-SOD and glutathione peroxidase activities. These findings show that the thyroid hormones might be able to regulate the activities of CuZn- and Mn-SOD, and catalase and glutathione peroxidase in the lymphoid organs and skeletal muscles.

Animals↗

PubMed1994

Superoxide dismutase, catalase and glutathione peroxidase activities in the lymphoid organs of diabetic rats.

The effect of alloxan-induced diabetes on CuZn- and Mn-superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) activities, as well as the content of thiobarbituric acid reactive substances (TBARs) were examined in rat lymphoid organs (mesenteric lymph nodes (MLN), thymus and spleen) and, for comparison, red and white muscle fibres. The capacity for generation of reduced equivalents was also evaluated by measuring the activities of glucose-6-phosphate dehydrogenase (pentose-phosphate pathway-cytosol) and citrate synthase (Krebs cycle-mitochondria). Diabetes raised the capacity for the generation of reducing equivalents in the lymphoid organs: in the mitochondria of the thymus and spleen and in the cytosol of the mesenteric lymph nodes and thymus. In muscles, diabetes reduced CuZn-SOD activity in soleus and raised the activity in gastrocnemius, and depressed the activities of catalase in soleus and of glutathione peroxidase in both soleus and gastrocnemius. In relation to the lymphoid organs, the spleen showed a decrease in the antioxidant enzyme activities (except for glutathione peroxidase), whereas the thymus showed an increased level (except for Mn-SOD), and the MLN presented a reduction in Mn-SOD and catalase activities and an increase in GPX activity caused by diabetes. The content of TBARs in the tissues followed the changes in GPX activity inversely: i.e. a decrease in the lymphoid organs (except in the spleen) and an increase in the muscles of diabetic rats compared with the control group. All these changes found in diabetic rats were reversed by insulin treatment and were not modified by the normalization of glycaemia.

Animals↗

PubMed1994

Metabolism of glucose, glutamine and pyruvate in lymphocytes from Walker 256 tumor-bearing rats.

This study examined the effect of Walker 256 tumor growth in vivo on the metabolism of glucose, glutamine and pyruvate in lymphocytes. A comparison between the metabolism of Walker 256 tumor cells obtained in vivo with that of lymphocytes was also carried out. Lymphocytes and tumor cells were isolated and incubated for 1 h for the following measurements: lactate production from glucose (5.6 mM) and pyruvate (3 mM), glutamate and aspartate formation from glutamine (3 mM) and decarboxylation of [U-14C]-glucose, [U-14C]-glutamine, [1-14C]-pyruvate and [3-14C]-pyruvate. The presence of the tumor increased lactate production (2.7-fold from glucose and 2-fold from pyruvate), decarboxylation of [U-14C]-glucose (3.7-fold) and [1-14C]-pyruvate (4.4-fold) and the formation of aspartate (6.3-fold) and glutamate (4.6-fold) from glutamine. The conversion of glucose to lactate and CO2 was higher in tumor cells as compared to lymphocytes. Tumor cells also showed a higher production of glutamate and an 8-fold increased decarboxylation rate of [U-14C]-glutamine in tumor cells, which was more active than that of lymphocytes even from tumor-bearing rats. Tumor growth stimulated glucose and glutamine metabolism in lymphocytes; however, the importance of this fact for the function of these cells remains to be elucidated.

Animals↗

PubMed1994

Effect of dietary vitamin E supplementation on macrophage metabolism during ageing. Study in rats fed fat-rich diets during ageing.

The effect of dietary vitamin E supplementation upon macrophage metabolism and function was examined in aged rats fed a balanced or a polyunsaturated-rich diet. The following parameters were studied: number of cells in the intraperitoneal cavity, maximal activity of hexokinase, citrate synthase, glucose-6-phosphate dehydrogenase, glutathione peroxidase and phosphate-dependent glutaminase. The consumption of glucose and the production of lactate, hydrogen peroxide and thiobarbituric reactive substances were measured in control ONCO-BCG injected rats. The results indicated that vitamin E has no significant effect on the values of the parameters studied in the macrophages of rats fed a balanced diet both for 3 (mature) or 17 months (aged). This antioxidant did not provoke any response on the changes caused by ageing the animals. However, several of the metabolic and functional alterations in macrophage induced by the polyunsaturated-rich diets were reversed by the inclusion of vitamin E in the diet. These changes were associated with macrophage migration capacity, citrate synthase and glucose-6-phosphate dehydrogenase activities and the content of lipid peroxides. The findings suggest that vitamin E has a beneficial effect for macrophage metabolism and function, but the effects are confined to particular circumstances.

Aging↗

PubMed1994

Evidence that prostaglandins modulate lipogenesis in cultured lymphocytes--a comparison with its effect on macrophages and tumour cells.

Lipogenesis is essential for the rapid proliferation of cells and it is established that the biosynthesis of selected lipids precedes S-phase, DNA synthesis and the initiation of cell division. Pyruvate was previously shown to be an important lipid precursor for lymphocytes, macrophages and tumour cells. This study now reports the role of prostaglandins (PG) on the regulation of lipogenesis from [3-14C] pyruvate in 24-h cultured lymphocytes. It is shown that indomethacin (10 microM) and ibuprofen (10 microM), both inhibitors of PG biosynthesis, increased [3-14C] pyruvate incorporations into phospholipid and cholesterol fractions in resting lymphocytes but reduced its incorporation into these fractions in concanavalin A (Con A)-stimulated lymphocytes and tumour cells. These two agents also affected [2-14C] thymidine incorporation into the DNA of these cells in the same manner. Lipids produced from [3-14C] pyruvate and exported into the cell culture medium were also measured. The PG biosynthesis inhibitions reduced the transfer to culture medium of arachidonic acid, phospholipids, cholesterol and fatty acids higher than C20 by lymphocytes and tumour cells. Although macrophages are not proliferative cells, the cytoplasmic export measurement is important because these cells have a high capacity for lipid secretion. The results show that the PG biosynthesis inhibitors do not affect the export of phospholipids and cholesterol in macrophages. They do however markedly change the export of arachidonic acid and fatty acids higher than C20 produced from [3-14C] pyruvate in macrophages. It is also reported that a cell-stimulating response diminished the above fatty acid outcome in resting cells and augmented it in thioglycollate-stimulated macrophages. The findings suggest that PG modulation of lipogenesis may depend on cell cycle phase as well as the intrinsic lipid metabolic diversity and capacity.

Acetates↗

PubMed1994

Blood glucose and lactate levels during hemorrhagic shock reversion by hypertonic NaCl solution.

1. Several studies have shown that in irreversible hemorrhagic shock the liver is one of the first vital organs to present metabolic alterations accompanied by an increase in lacticemia. Intravenous infusion of hypertonic solutions increases mesenteric flow as well as liver perfusion, an effect which can be blocked by vagotomy. 2. In the present study we investigate the possible role of the increase in mesenteric flow in the prevention of hepatic failure evaluated by the arterial-venous difference in the generation of glucose from lactate during the reversal of hemorrhagic shock with hypertonic NaCl solution and the possible blockage of this response by bilateral vagotomy. 3. Twenty-eight male dogs, weighing 14-20 kg, were submitted to severe hemorrhagic shock. The animals were then divided into four groups: a) HYPER, 2400 mosm/l NaCl; b) SALINE, 300 mosm/l NaCl; c) HYPERVg, 2400 mosm/l NaCl immediately after bilateral vagotomy; d) SALINEVg, 300 mosm/l NaCl immediately after bilateral vagotomy. Each group received an intravenous infusion of 10% of the shed blood volume of NaCl infusion. 4. Arterial and venous samples were collected to monitor the levels of lactate, glucose and insulin. During hemorrhage, arterial and venous lactate concentrations increased. After infusion, arterial lactate levels decreased from 332 +/- 23% to 115 +/- 12% in the HYPER group in contrast to the SALINE group where it increased from 327 +/- 20% to 422 +/- 19%. 5. The decrease in arterial lactate observed after hypertonic solution infusion (2400 mosm/l), in dogs with intact vagus, suggests an increase of lactate uptake by heart and liver. Thus the beneficial effect of hypertonic solution in the reversal of hemorrhagic shock may be to enhance blood flow and oxygen delivery to the liver which would maintain glucose production and prevent hepatic failure. All the metabolic effects of hypertonic solution were abolished by vagotomy.

Animals↗

PubMed1994

Pyruvate carboxylase activity in the heart and skeletal muscles of the rat. Evidence for a stimulating effect of exercise.

The mitochondrial pyruvate carboxylase catalyses the ATP-dependent carboxylation of pyruvate to oxaloacetate. Since pyruvate carboxylase generates oxaloacetate for Krebs cycle function, it is proposed that the enzyme activity may be enhanced by exercise. To investigate this proposition, pyruvate carboxylase activity was determined in the heart, soleus and gastrocnemius (white portion) muscles of sedentary and swimming-trained adult rats (1 hour per day, 5 days a week, during 5 weeks) under the following conditions: rest, one hour of exercise and exhaustion. The results show that the pyruvate carboxylase activity is increased during exercise in both the sedentary and trained groups of rats. The stimulatory mechanism is unknown but it is possibly related to the generation of pyruvate from the breakdown of glycogen and acetyl CoA during fatty acid oxidation.

Analysis of Variance↗

PubMed1993

Thioglycollate stimulus modifies lymphocyte metabolism and proliferation. A comparison with lymphocyte activation by Walker 256 tumour implantation.

Key enzyme activities of glycolysis, the pentose-phosphate pathway, the Krebs' cycle and glutaminolysis were measured in lymphocytes obtained from the control (CC), thioglycollate-injected (TG) and Walker 256 tumour-implanted (WT) groups, non-immune and immune inflammatory stimuli, respectively. The rates of incorporation of [2-14C]-thymidine and [5-3H]-uridine into cultured lymphocytes were also determined. The results indicated that the rates of both [2-14C]-thymidine and [5-3H]-uridine incorporation were enhanced in lymphocytes obtained from thioglycollate-injected (by an average of 80 per cent) and tumour-implanted animals (by 2.4-fold) as compared to control rats. Lymphocyte hexokinase activity diminished both in the TG (23 per cent) and WT (61 per cent) groups, whereas glucose 6-phosphate dehydrogenase activity was not altered due to the non-immune inflammatory stimulus, being reduced (23 per cent) in WT rats as compared to CC. The activity of lymphocyte citrate synthase was lowered by thioglycollate (39 per cent) and tumour-implantation (46 per cent). In contrast, glutaminase activity was augmented in lymphocytes from the TG (41 per cent) and was not modified in the WT groups. Taken as a whole, the presence of the Walker 256 tumour did not affect the capacity for glutamine utilization but depressed glucose metabolism in these cells. On the other hand, the non-immune inflammatory stimulus suppressed the activities of glycolysis and the Krebs' cycle and enhanced that of glutaminolysis in lymphocytes.

Animals↗

PubMed1993

Effect of fatty acid-rich diets on thymocyte proliferation and thymus involution during growing.

The effect of poly-unsaturated and saturated fatty acid-rich diet on the proliferation response of T and B lymphocytes in vitro was investigated. Also, a mitotic index of thymocytes and of thymus epithelial reticular-like cells and thymic involution coefficient were examined in vivo. w-6 PUFA-rich diet enhanced the rate of T (eightfold) and B (fourfold) lymphocyte proliferation, whereas saturated fatty acids did not show an important effect. However, both fat-rich diets increased the mitotic index of thymocytes and thymus involution index in vivo. These findings suggest that fat-rich diets may accelerate thymus involution during growing, possibly aggravating the impairment of the immune function which usually occurs under this condition.

Aging↗

PubMed1993

Metabolic and functional changes in lymphocytes and macrophages as induced by ageing.

Key enzyme activities of glycolysis, pentosephosphate pathway, Krebs cycle, and glutaminolysis were measured in lymphocytes and macrophages of 3- and 15-month-old rats from the control, thioglycollate-injected, and Walker 256 tumor-implanted groups. The percentage of phagocytosis, phagocytic index, and production of H2O2 in macrophages and the rates of [2-14C]-thymidine and [5-3H]-uridine incorporation in cultured lymphocytes were also determined. The results indicate that the percentage of phagocytosis was not affected but the phagocytic index increased by twofold as a consequence of ageing, whereas the production of H2O2 reduced. The rates of both [2-14C]-thymidine and [5-3H]-uridine incorporation in lymphocytes from aged rats were lower as compared to those of mature animals in the three groups. Taken as a whole, the results of enzyme activities suggest that ageing may reduce the capacity for glucose utilization in lymphocytes and macrophages under the three conditions. Lymphocyte and macrophage glutamine metabolism was not markedly affected by ageing. Therefore, an impaired glucose metabolism during ageing may be one important mechanism for the alteration in lymphocyte proliferation and macrophage phagocytosis observed and also for the modification of the response to inflammatory and tumor challenges.

Aging↗

PubMed1993

Propionate regulates lymphocyte proliferation and metabolism.

1. The effect of propionate on lymphocyte proliferation and metabolism was investigated. Lymphocytes obtained from human blood and rat mesenteric lymph nodes were utilized. 2. Propionate at concentrations of 0.04 and 1.0 mmol/l stimulated the amount of [3H]thymidine incorporated either in cultured human T lymphocytes or rat T and B lymphocytes. 3. Concentrations of propionate between 2 and 5 mmol/l caused a marked inhibition of lymphocyte proliferation. 4. This short-chain fatty acid was metabolized by these cells and produced succinate in significant amounts; however, its oxidation was low. 5. Propionate did not alter glucose, glutamine and pyruvate utilization and oxidation in incubated rat lymphocytes but increased the formation of lactate and aspartate. 6. In contrast, propionate inhibited by 50% the synthesis of lymphocyte lipid from [1-14C]acetate at concentrations of 0.5 and 1 mmol/l and reduced by half the incorporation of 3H2O into lipids at 1 and 5 mmol/l. 7. The results suggest that inhibition of lipid synthesis is a possible mechanism leading to reduction of lymphocytes proliferation.

Adult↗

PubMed1993

Effect of epinephrine on 86Rb efflux, 45Ca outflow and insulin release from pancreatic islets perifused in the presence of propranolol.

Pancreatic islets prelabelled with either 86Rb or 45Ca were perifused in the presence of propranolol (0.1 microM) and, when required, exposed to epinephrine (0.1 microM). In the absence of D-glucose, epinephrine failed to cause any obvious change in either 86Rb or 45Ca outflow. In the presence of 16.7 mM D-glucose, however, epinephrine lowered both 86Rb and 45Ca outflow, this coinciding with suppression of insulin release. Epinephrine also suppressed the increment in 86Rb outflow evoked by a rise in glucose-concentration from 8.3 to 16.7 mM. Epinephrine did not abolish the early fall in 45Ca efflux evoked by the administration of D-glucose (16.7 mM) to islets previously deprived of the hexose but, within the same experiments, impaired the secondary rise in effluent radioactivity. Likewise, epinephrine prevented the increase in 45Ca outflow provoked by a rise in hexose concentration from 8.3 to 16.7 mM. These findings are compatible with the recent proposal that epinephrine interferes with the entry of Ca2+ into the B-cell, as mediated by voltage-sensitive Ca2+ channels, but do not rule out a multifactorial coupling between the occupancy of alpha 2-adrenergic receptors and the eventual inhibition of insulin release.

Animals↗