Inhibition of the NADP-linked glutamate dehydrogenase fromTrypanosoma cruzi by silver nitrate

Summary The purified NADP-linked glutamate dehydrogenase fromTrypanosoma cruzi was strongly inhibited by silver nitrate. The inhibition was reversed by reduced glutathione, and was modified by the presence of the substrates during preincubation of the enzyme with the inhibitor.This work was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina and the Secretaría de Estado de Ciencia y Technología de la República Argentina. JJC is a member of the Carrera del Investigador Científico, and SMJ a Research Fellow, of the former Institution.     

Effect of the rat liver S9 fraction on the mutagenicity of azathioprine in theSalmonella/mammalian microsome assay

Summary Azathioprine is a direct acting mutagen inSalmonella typhimurium TA100 and TA1535. Addition of rat liver S9 fraction with or without co-factors, or glutathione, causes a decrease in the mutagenicity of azathioprine in TA100 and an increase in TA1535, indicating the effect of SH groups.Acknowledgments. This work was supported in part by a grant from SECYT (Argentina).     

Effect of the rat liver S9 fraction on the mutagenicity of azathioprine in the Salmonella/mammalian microsome assay

Azathioprine is a direct acting mutagen in Salmonella typhimurium TA100 and TA1535. Addition of rat liver S9 fraction with or without co-factors, or glutathione, causes a decrease in the mutagenicity of azathioprine in TA100 and an increase in TA1535, indicating the effect of SH groups.     

Inhibition of cholesterol synthesis ex vivo and in vivo by fluvastatin,a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase

The inhibitory effect of fluvastatin sodium (fluvastatin), a new type of 3-hydroxy-3-methylglutaryl (HMG) coenzyme A inhibitor, on de novo cholesterol synthesis was investigated and compared with that of pravastatin. Fluvastatin at a concentration of 12.5 mg/kg inhibited sterol synthesis ex vivo from [¹⁴C]acetate in rat liver and ileum by 97–99% with respect to the control, while the inhibition in kidney was 55%. The inhibition by fluvastatin in the liver and ileum persisted for approximately 9 h after administration. Significant differences between fluvastatin also had an inhibitory effect on cholesterol synthesis in vivo in various tissues of rats given [¹⁴C]acetate intraperitoneally. Sterol synthesis in the liver, ileum and kidney was inhibited by over 95% 3 h after administration of 6.25 mg/kg of fluvastatin. Significant differences between fluvastatin and pravastatin were found in the liver and ileum. Fluvastatin was more potent than pravastatin in inhibiting both ex vivo and in vivo sterol synthesis in the ileum (but not in kidney) and liver.     

Chronic hydrogen peroxide intake and peroxide metabolizing enzyme activities in some tissues of mice and rats

Chronic daily intake of 0.5% H2O2 in drinking water decreased Se-dependent glutathione peroxidase (Se-GSHPx) activity in rat skeletal muscle, kidney and liver. Non-Se GSHPx activity decreased in kidney. Deprivation of drinking water decreased Se-GSHPx activity in kidney and non-Se GSHPx activity in kidney and liver. H2O2 intake decreased activity of catalase in rat skeletal muscle. H2O2 intake or water deprivation caused no changes in these enzyme activities in mice.     

Effects of probenecid on plasma/tissue distribution of14C-benzylpenicillin in rats

Summary Probenecid (50 mg·kg^–1) was found to induce an increase of the plasma concentration of¹⁴C-benzylpenicillin with a decrease of the concentration in liver and kidney. Accumulation in corresponding tissue slices was reduced by probenecid. Therefore, the well known increase of penicillin in plasma after probenecid seems to be not only due to an inhibition of renal excretion but also to a reduced tissue uptake in liver and kidney.     

Glutathione andγ -glutamyl cycle enzymes in rat mammary gland

Summary The main enzymes of theγ-glutamyl cycle during the lactogenic cycle in rat mammary gland were studied. A significant increase was found in all of them with the onset of lactogenesis. The effect of methionine sulfoximine on reduced glutathione concentration was studied in tissue slices of lactating mammary gland. The findings suggest that this compound affects glutathione synthesis by inhibitingγ-glutamylcysteine synthetase. This work was supported by grant B1138-8223 from the Servicio de Desarrollo Cientifico, Universidad de Chile.     

Effects of chronic caffeine feeding on the activities of oxygen free radical defense enzymes in the growing rat heart and liver

The purpose of the present study was to determine the relationship between concentration of Zn, Cu and Fe, and the catalase, glutathione peroxidase and superoxide dismutase activities in the heart and liver of newborn rats whose dams were fed a diet supplemented with caffeine. Heart Zn levels of the 22- and 30-day-old rats of the caffeine group showed a decrease, whereas liver Zn levels showed an increase compared to the control. Cu levels in the liver at day 22 in the caffeine group were less than in the control. Cu- and Zn-containing superoxide dismutase activities showed an increase in the hearts of the caffeine group compared to the control. The activity of catalase and glutathion peroxidase showed no difference in the heart and liver between the groups. The present study suggests the possible involvement of superoxide dismutase enzyme in the impairment of heart formation as a result of chronic caffeine intake in the early growing period.     

Early effects of copper accumulation on methionine metabolism

Wilson's disease is characterized by longterm hepatic accumulation of copper leading to liver disease with reduction of S-adenosylmethionine synthesis. However, the initial changes in this pathway remain unknown and constitute the objective of the present study. Using the Long Evans Cinnamon rat model, early alterations were detected in the mRNA and protein levels, as well as in the activities of several enzymes of the methionine cycle. Notably, the main change was a redox-mediated 80% decrease in the mRNA levels of the methionine adenosyltransferase regulatory subunit as compared to the control group. Moreover, changes in S-adenosylmethionine, S-adenosylhomocysteine, methionine and glutathione levels were also observed. In addition, in vitro experiments show that copper affects the activity and folding of methionine adenosyltransferase catalytic subunits. Taken together, these observations indicate that early copper accumulation alters methionine metabolism with a pattern distinct from that described previously for other liver diseases.     

Effects of Freund's complete adjuvant on the dirunal rhythms of neuroendocrine processes and ornithine decarboxylase activity in various tissues of male rats

The aim of this study was to investigate the effects of Freund's complete adjuvant (FCA) on the diurnal rhythms of hormonal parameters in serum and ornithine decarboxylase (ODC) activity in various tissues of male rats. On days 1–2 after FCA, increase of ODC activity (used to evaluate the level of activation) was observed in the hypothalamus, pituitary gland, adrenal medulla, adrenal cortex, liver and lymphoid tissues, while the ODC activity in the kidney was reduced. This was accompanied by an increase in serum corticosterone. On days 3–4 after FCA, ODC activity remained elevated in the pituitary gland, liver and lymphoid tissues, while the ODC activity in the testes and panceas was reduced; kidney ODC activity returned to baseline. This was associated with increased serum levels of prolactin (Prl) and luteinizing hormone, but decreased growth hormone, testosterone and insulin. The increase in ODC activity in the thymus, as well as the reduced ODC activity in the testes and kidney, can be obtained with paraffin. Furthermore, bromocryptine microcapsules (CBLA) reduced the FCA-induced increase of ODC activity in the pituitary gland, liver and lymphoid tissues (days 3–4) but did not affect the changes in other tissues. The increase in ODC activity in the pituitary gland, liver and lymphoid tissues is specific for FCA. A role for Prl in the induction of ODC in liver and lymphoid tissues is suggested by the fact that CBLA suppresses this enhancement.     

Chronic hydrogen peroxide intake and peroxide metabolizing enzyme activities in some tissues of mice and rats

Summary Chronic daily intake of 0.5% H₂O₂ in drinking water decreased Se-dependent glutathione peroxidase (Se-GSHPx) activity in rat skeletal muscle, kidney and liver. Non-Se GSHPx activity decreased in kidney. Deprivation of drinking water decreased Se-GSHPx activity in kidney and non-Se GSHPx activity in kidney and liver. H₂O₂ intake decreased activity of catalase in rat skeletal muscle. H₂O₂ intake or water deprivation caused no changes in these enzyme activities in mice.     

The effect of polysaccharide-protein complex isolated from Candida albicans on regional blood flow in rats.

After i.v. administration to rats of polysaccharide-protein complex, isolated from Candida albicans, a decrease of cardiac output was observed from 20 sec to 240 min postinjection, followed by a recovery at 360 min. Concomitantly the regional blood flow was maintained in heart and lungs, moderately decreased in intestine, liver and adrenals and markedly reduced in skin, muscle, spleen and kidney.     

Immunohistochemical localization fo galactocerebroside in kidney,liver, and lung of golden hamster

Summary Localization of galactocerebroside in kidney, liver, and lung of hamster was studied by the immunoperoxidase method using an affinity-purified specific antibody. Epithelial cells of the following anatomical sites were labelled with the antibody: distal tubuli, ascending limbs of Henle's loops, and collecting tubuli in kidney; periportal bile ducts and hepatic parenchyma in liver; bronchioli and alveoli in lung. The existence of galactocerebroside in these 3 organs was also confirmed by chemical analysis.This study was supported in part by grants from the Ministry of Education, Science and Culture of Japan, a Research Grant for Intractable Diseases from the Ministry of Health and Welfare of Japan, and a grant from the Mitsubishi Foundation.     

Effect of latent iron deficiency on the levels of iron, calcium, zinc, copper, manganese, cadmium and lead in liver, kidney and spleen of growing rats

Feeding a marginally low iron content diet (18-20 mg iron/kg diet) to weaned (21-day-old) rats for 8 weeks produced a significant decrease in liver non-heme iron (66%, p less than 0.001) but no change in blood hemoglobin. Total iron contents of liver (56%, p less than 0.01), spleen (20%, p less than 0.05), and kidney (19%, p less than 0.05) were also found to decrease along with increased zinc, copper, calcium, manganese lead and cadmium in various organs. The magnitude of alteration of a metal was different in different organs. However, liver was found to be the most affected organ. Two weeks of rehabilitation with iron-sufficient diet (390 mg iron/kg diet) normalized these altered levels.     

Effect of latent iron deficiency on the levels of iron,calcium, zinc,copper, manganese,cadmium and lead in liver,kidney and spleen of growing rats

Summary Feeding a marginally low iron content diet (18–20 mg iron/kg diet) to weaned (21-day-old) rats for 8 weeks produced a significant decrease in liver non-heme iron (66%, p<0.001) but no change in blood hemoglobin. Total iron contents of liver (56%, p<0.01), spleen (20%, p<0.05), and kidney (19%, p<0.05) were also found to decrease along with increased zinc, copper, calcium, manganese lead and cadmium in various organs. The magnitude of alteration of a metal was different in different organs. However, liver was found to be the most affected organ. Two weeks of rehabilitation with iron-sufficient diet (390 mg iron/kg diet) normalized these altered levels.     

Influence of nocloprost on the vascular responses to various stimuli in the isolated perfused rabbit kidney

Summary Nocloprost, a new synthetic prostanoid, elicited a vasodilator action when given through the renal artery of the isolated perfused rabbit kidney. Lower concentrations of the compound inhibited the pressor response to sympathetic stimulation or to angiotensin II, but potentiated the pressor effect of exogenous noradrenaline. These results were taken as an evidence that nocloprost prevents the release of neurotransmitter by a presynaptic mechanism.This work was supported by a grant from the Turkish Scientific and Technical Research Council (TAG-578). Nocloprost is the gift of Dr E. Schillinger, Head of Biochemical Pharmacology, Schering AG Research Laboratories, Berlin, FRG.     

The effect of polysaccharide-protein complex isolated fromCandida albicans on regional blood flow in rats

Summary After i.v. administration to rats of polysaccharide-protein complex, isolated fromCandida albicans, a decrease of cardiac output was observed from 20 sec to 240 min postinjection, followed by a recovery at 360 min. Concomitantly the regional blood flow was maintained in heart and lungs, moderately decreased in intestine, liver and adrenals and markedly reduced in skin, muscle, spleen and kidney.     

Osmotic fragility and lipid peroxidation of irradiated erythrocytes in the presence of radioprotectors

Summary Gamma radiation causes a decrease in the osmotic fragility of porcine erythrocytes and induces peroxidation of membrane lipids, as reflected by an increase in malondialdehyde content. With respect to osmotic fragility all the protectors used have the radioprotective effect. Malondialdehyde content was reduced in the presence of catalase, cysteine and glutathione, whereas SOD had no protective effect.This work was performed under the contract R.III.13.     

The effect of sulfhydryl compounds on the catalytic activity of Cu, Zn-superoxide dismutase purified from rat liver

Sulfhydryl compounds such as reduced glutathione, cysteine and 2-mercaptopropionylglycine, a hepato-protective agent, activated Cu, Zn-superoxide dismutase purified from rat liver at low concentrations (below 10 microM). Furthermore we found evidence indicating that this activation is achieved by reducing Cu2+ present in the catalytic site of the dismutase, and thereby promoting the dismutation of superoxide anions.     

Hemolysis and peroxidation in heavy metal-treated erythrocytes; GSH content and activities of some protecting enzymes

Summary The activities of superoxide dismutase, catalase and glutathione peroxidase, and the level of reduced glutathione, were measured in heavy metal-treated erythrocytes. The hemolytic metals were found to significantly deactivate both catalase and glutathione peroxidase and to decrease the level of reduced glutathione, thus providing suitable conditions for the development of peroxidation.