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Biomedical subjects

J Viña

Publications and source records attributed to J Viña.

At least 55 records · Page 3Linked to original sources
PubMed1992

Effect of aging on glutathione metabolism. Protection by antioxidants.

The free radical theory of aging suggests that oxygen free radicals may be involved in the aging process. Thus, changes in antioxidant mechanisms may occur with aging. Since glutathione is one of the most effective antioxidant systems in the cell, its metabolism may change with aging. In this chapter we describe experiments which show the involvement of glutathione in the aging process and which provide a rationale for the administration of antioxidants to old organisms to protect them against some of the changes that occur with aging.

Aging↗
PubMed1992

Effect of aging on metabolic zonation in rat liver: acinar distribution of GSH metabolism.

The effect of age on the glutathione antioxidant system and its acinar distribution in rat liver was studied. GSH/GSSG ratio in blood and liver was lower in old than in young rats. Hepatic glutathione peroxidase and glutathione S-transferase activities were higher in old than in young rats, whereas hepatic gamma-glutamyl transpeptidase activity was lower in old than in young rats. Glutathione reductase and glucose-6-phosphate dehydrogenase activities did not change with age in rat liver. Total glutathione levels and glutathione peroxidase activity were higher in periportal than in perivenous areas of young rats, but this heterogeneous distribution did not occur in old rats. No change with age was found in hepatic zonation of glutathione reductase and glucose-6-phosphate dehydrogenase.

Aging↗
PubMed1992

Impairment of cysteine synthesis from methionine in rats exposed to surgical stress.

The activity of liver cystathionase (EC 4.4.1.1) was decreased after 3 d of stress induced by surgery. The rate of L-cysteine synthesis from L-methionine was significantly higher in isolated hepatocytes from controls than in hepatocytes from rats suffering from surgical stress. The half-life of L-[2(n)-3H]methionine was significantly higher in rats submitted to surgical stress than in controls. Plasma L-methionine:L-cystine ratio was higher in stressed rats than in controls. L-cystine uptake was significantly increased in the surgically-stressed rats when compared with the controls. All these facts are consistent with the hypothesis that the observed inhibition of cystathionase is physiologically important and that L-cysteine might be considered as an essential amino acid in cases of surgical stress.

Acetylcysteine↗
PubMed1992

Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration.

We have studied the effect of exhaustive concentric physical exercise on glutathione redox status and the possible relationship between blood glutathione oxidation and blood lactate and pyruvate levels. Levels of oxidized glutathione (GSSG) in blood increase after exhaustive concentric physical exercise in trained humans. GSSG levels were 72% higher immediately after exercise than at rest. They returned to normal values 1 h after exercise. Blood reduced glutathione (GSH) levels did not change significantly after the exercise. We have found a linear relationship between GSSG-to-GSH and lactate-to-pyruvate ratios in human blood before, during, and after exhaustive exercise. In rats, physical exercise also caused an increase in blood GSSG levels that were 200% higher after physical exercise than at rest. GSH levels did not change significantly. Thus, both in rats and humans, exhaustive physical exercise causes a change in glutathione redox status in blood. We have also found that antioxidant administration, i.e., oral vitamin C, N-acetyl-L-cysteine, or glutathione, is effective in preventing oxidation of the blood glutathione pool after physical exercise in rats.

Animals↗
PubMed1991

Significance of gamma-glutamyltranspeptidase in exocrine pancreatic amino acid transport.

The exocrine pancreas is rich in gamma-glutamyltranspeptidase (GGT, EC 2.3.2.2) and exhibits high rates of amino acid transport and protein synthesis. The role of the gamma-glutamyl cycle in mediating neutral amino acid transport in the isolated perfused rat pancreas was investigated using acivicin, an inhibitor of GGT, and a rapid dual isotope dilution technique. When treatment in vivo with acivicin (50 mg/kg) was followed 1 h later by continuous perfusion of the isolated pancreas with 10 microM acivicin, GGT levels decreased from 53 +/- 3 IU/g to 4.9 +/- 1.5 IU/g. This marked inhibition of GGT activity was not associated with decreased uptake for either L-alanine or L-glutamine, suggesting that the gamma-glutamyl cycle plays a negligible role in amino acid transport across the basolateral membrane of the pancreatic epithelium.

Alanine↗
PubMed1991

Physiological changes in glutathione metabolism in foetal and newborn rat liver.

Glutathione metabolism was studied in isolated hepatocytes from foetal, newborn and adult rats. The GSH/GSSG ratio decreased 15-20-fold through the foetal-neonatal-adult transition. This was mainly due to an increase in GSSG. All enzyme activities involved in the glutathione redox cycle tend to increase during that transition, but the relative increases in glutathione peroxidase and glutathione S-transferase were 3-5 times those of glutathione reductase or glucose-6-phosphate dehydrogenase. GSH synthesis from methionine as a sulphur source was 6 times lower in foetal than in adult hepatocytes. However, when N-acetylcysteine was used as a sulphur donor to by-pass the cystathionine pathway, the rates of GSH synthesis were similar in foetal and adult cells. This is due to the fact that cystathionase activity in foetal cells is very low. This low activity is reflected in the blood amino acid pattern, where the concentration of cysteine rises from 8 to 52 microM from foetuses to adult rats. This supports the idea that cysteine may be an essential amino acid for the premature animal.

Aging↗
PubMed1991

Inhibition of gluconeogenesis by extracellular ATP in isolated rat hepatocytes.

The aim of this study was to determine the effect of externally added ATP on gluconeogenesis by isolated hepatocytes from starved rats. High concentrations of extracellular ATP inhibited gluconeogenesis from lactate and pyruvate but not from glycerol or fructose. This inhibition was associated with an increase in intracellular adenosine contents. ADP, AMP, or adenosine but not guanosine 5'triphosphate, inosine 5' triphosphate, or adenine also inhibited gluconeogenesis. alpha, beta-Methylene-ATP, a nonmetabolizable structural analogue of ATP, did not affect the rate of gluconeogenesis. Intracellular ATP levels were increased by externally added ATP or adenosine, but ATP-to-ADP ratios in the cytosolic and mitochondrial compartments were diminished. Malate and phosphoenolpyruvate contents were decreased by extracellular ATP or adenosine. Our results show that inhibition of gluconeogenesis by high levels of extracellular ATP may be mediated by adenosine derived from ATP catabolism at the plasma membrane.

Adenosine Diphosphate↗
PubMed1990

Inhibition of gamma-glutamyl transpeptidase decreases amino acid uptake in human keratinocytes in culture.

Acivicin inhibits gamma-glutamyl transpeptidase activity in human keratinocytes in culture. Treatment of these cells with acivicin produces a decrease in the uptake of L-[U-14C]alanine, 2-amino-[1-14C]-isobutyrate, L-[U-14C]leucine and 1-aminocyclopentane-1-[14C]carboxylate. D-[U-14C]glucose uptake is not affected by the presence of acivicin. These results support, for the first time in vitro, the hypothesis that the gamma-glutamyl cycle may be involved in amino acid uptake by human cells.

Amino Acids↗
PubMed1990

Age-related changes in glutathione synthesis in the eye lens.

Eye lenses from young rats or mice synthesize GSH from methionine or N-acetylcysteine. However, lenses from old animals do not synthesize GSH from methionine. This is due to the absence of cystathionase activity in old lenses. GSH monoethyl ester, but not free GSH, increases GSH content and protects the lens against experimental oxidative stress. The importance of these results in the prevention of cataractogenesis is discussed.

Acetylcysteine↗
PubMed1989

Glutathione depletion by hyperphagia-induced obesity.

Reduced glutathione (GSH) levels in freeze-clamped livers of rats and mice in which hyperphagia is induced by cafeteria diet are 45% lower than in controls. Freshly isolated hepatocytes from mice fed cafeteria diet show a 45% decrease in GSH concentration and a 54% decrease in oxidized glutathione (GSSG) concentration when compared with controls. The rate of GSH synthesis in isolated hepatocytes from control mice is significantly higher than in those from mice fed cafeteria diet. Oral GSH is effective to prevent the decrease in hepatic GSH levels found in cafeteria fed mice.

Animals↗
PubMed1989

Effect of oral glutathione on hepatic glutathione levels in rats and mice.

Administration of oral glutathione (GSH) increases hepatic GSH levels in fasted rats, in mice treated with GSH depletors such as diethyl maleate and in mice treated with high doses of paracetamol. An increase in hepatic GSH levels after administration of oral GSH does not occur in animals treated with buthionine sulphoximine, an inhibitor of GSH synthesis. Administration of oral GSH leads to an increase in the concentration of L-cysteine, a precursor of GSH, in portal blood plasma. Oral administration of L-methionine produced a significant decrease of hepatic ATP in fasted rats, but not in fed rats. Administration of N-acetylcysteine or GSH did not affect the hepatic ATP levels. The results show that the oral intake of GSH is a safe and efficient form of administration of its constituent amino acids in cases when GSH synthesis is required to replete hepatic GSH levels.

Acetaminophen↗
PubMed1989

Role of the gamma-glutamyl cycle in the regulation of amino acid translocation.

Amino acid translocation was studied in the mammary gland of lactating rats and in the placenta of pregnant rats. The uptake of amino acids by the mammary gland is maximal on days 10-14 of lactation and is minimal on days 19-21. However, on day 19 maximal uptake can be restored by injection of 1) small amounts of gamma-glutamyl amino acids, 2) 5-oxoproline, and 3) an inhibitor of 5-oxoprolinase. A severe decrease in uptake of amino acids at the peak of lactation is provoked by anthglutin, an inhibitor of gamma-glutamyltranspeptidase (GGT). Simultaneous injection of 5-oxoproline blocks these effects of anthglutin. In pregnant rats, inhibition (79%) of placental GGT activity by acivicin results in a 50% decrease of placental L-[U-14C]-alanine transfer and 70-80% decrease in its incorporation into the placental and fetal proteins. Infusion of 5-oxoproline to mothers previously treated with acivicin restored the L-[U-14C]-alanine transfer. Acivicin or 5-oxoproline did not modify the transfer and metabolism of D-[U14C]glucose by the fetal placental unit. These results show that the gamma-glutamyl cycle should not be considered a mechanism for amino acid transport but rather a generator of extracellular signals, gamma-glutamyl amino acids, that are converted intracellularly to 5-oxoproline, which activates uptake and/or metabolism of amino acids.

Alanine↗
PubMed1988

Alpha-adrenergic modulation of glutathione metabolism in isolated rat hepatocytes.

Glutathione metabolism was studied in isolated hepatocytes from 48-h starved rats. Phenylephrine (10 microM, final concentration) was incubated in the presence of a mixture of L-glutamine, glycine, L-serine, and L-methionine (at 10 times their normal plasma concentration). Alpha-adrenergic stimulation provoked a decrease in glutathione (GSH) synthesis. This effect was accompanied by an enhanced efflux of glutathione from the cells. Phenylephrine stimulated the rate of glutathione disulfide (GSSG) formation; however, this effect was clearly insufficient to explain the disappearance of GSH. Our results suggest that the decrease in cellular GSH levels observed under conditions of shock, stress, or peripheral inflammation can be explained by a dual effect, i.e., an increase in glutathione efflux and an inhibition of its synthesis.

Amino Acids↗
PubMed1987

Glutathione metabolism under the influence of hydroperoxides in the lactating mammary gland of the rat. Effect of glucose and extracellular ATP.

Tert-butyl hydroperoxide decreases GSH and total free glutathione (GSH + 2GSSG) contents of acini from lactating mammary glands. The decrease in total free glutathione can be explained by an increase in mixed disulfide formation and by excretion of GSSG to the extracellular medium, and subsequent degradation catalyzed by gamma-glutamyl transpeptidase. Low concentrations of glucose prevented the changes in glutathione levels induced by the peroxide. In the presence of extracellular ATP, glucose did not prevent these changes. However, incubations with the peroxide, did not alter the rate of other metabolic pathways by acini.

Adenosine Triphosphate↗
PubMed1987

Effect of fasting on amino acid metabolism by lactating mammary gland: studies in women and rats.

Concentrations of free amino acids were measured in human milk and arterial blood from lactating women after an overnight fast or after a controlled breakfast. The concentrations of many free amino acids in milk (except L-tyrosine, L-aspartate, L-asparagine, L-glutamate and L-glutamine) were lower after an overnight fast than after breakfast. Similarly, the arterial concentrations of amino acids were lower except for L-asparagine, L-alanine, L-tyrosine and L-phenylalanine. Net uptake of amino acids by the mammary gland of the lactating rat was significantly lower after starvation for 6 or 24 h than in the fed state because the arteriovenous differences of amino acids and the blood flow were significantly lowered. Starvation produced a significant decrease of 2-amino-[1-14C]isobutyric acid uptake by isolated acini from lactating rat. These results show that short-term starvation decreases the amino acid supply and transport in mammary gland as well as the free amino acid concentration in milk.

Amino Acids↗
PubMed1985

Decreased urea synthesis in cafeteria-diet-induced obesity in the rat.

Feeding rats with a cafeteria diet resulted in increases in total body weight and in epididymal-adipose-tissue weight. Those rats excreted significantly less N than did controls. The amount of N ingested by cafeteria-diet-fed rats was kept equal to that of controls. This decrease in N excretion is explained by a decrease in urinary excretion of urea. This may be due to the following facts. The rate of synthesis of urea from precursors by isolated hepatocytes from cafeteria-diet-fed rats was lower than in controls. In cafeteria-diet-fed rats the activities of all the enzymes of the urea cycle are decreased. The major percentage decreases are those of carbamoylphosphate synthetase (EC 6.3.4.16) and of argininosuccinate synthetase (EC 6.3.4.5), the enzymes probably involved in the regulation of the overall rate of the cycle. When rats are switched to normal chow diet, the enzyme activities return to normal values. The uptake of amino acids by liver of cafeteria-diet-fed rats is lower than in controls. These results contrast with those obtained previously by using other models of obesity in rat (i.e. genetic or hypothalamic), in which N excretion was increased.

Amino Acids↗
PubMed1985

Effects of glutathione depletion on gluconeogenesis in isolated hepatocytes.

Glutathione-depleted hepatocytes, by incubation with diethylmaleate (DEM) or phorone (2,6-dimethyl-2,5-heptadiene-4-one), i.e., substrates of the GSH S-transferases (EC 2.5.1.18), showed rates of gluconeogenesis from various precursors significantly lower than controls; however the rate of glucose synthesis from fructose was similar to that of controls. Isolated hepatocytes from rats pretreated with those substrates 1 h before isolation to deplete hepatic glutathione (GSH) also showed a decrease of the rate of gluconeogenesis from lactate plus pyruvate. Incubation of hepatocytes with L-buthionine sulfoximine, a specific inhibitor of gamma-glutamyl-cysteine synthetase (EC 6.3.2.2), resulted in a decreased rate of gluconeogenesis from lactate plus pyruvate only when GSH values were lower than 1 mumol/g cells. Freeze-clamped livers from GSH-depleted rats showed a higher concentration of malate and glycerol 3-phosphate, indicating that GSH depletion probably affects phosphoenolpyruvate carboxykinase and glycerol-3-phosphate dehydrogenase activities. Several indicators of cell viability, such as lactate dehydrogenase leakage, malondialdehyde accumulation, ATP concentration, or urea synthesis from different precursors, were not affected by GSH depletion under the experimental conditions used here. Besides, the GSH/GSSG ratio remained unchanged in all cases.

Adenosine Triphosphate↗