Inhibitory Effect of Thyroxine Analogues on Oxygen Consumption in Mice

Nature ◽  
1949 ◽  
Vol 164 (4173) ◽  
pp. 699-700 ◽  
Author(s):  
N. F. MACLAGAN ◽  
M. M. SHEAHAN ◽  
J. H. WILKINSON
Keyword(s):  
Oxygen Consumption ◽  
Inhibitory Effect

Halothane Selectively Inhibits Nonshivering Thermogenesis 

1995 ◽  
Vol 82 (2) ◽  
pp. 491-501 ◽  
Author(s):  
Andrea Dicker ◽  
Kerstin B. E. Ohlson ◽  
Lennart Johnson ◽  
Barbara Cannon ◽  
Sten G.E. Lindahl ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Inhibitory Effect ◽  
Nonshivering Thermogenesis ◽  
Halothane Anesthesia ◽  
Control Series ◽  
Mechanically Ventilated ◽  
Anesthetized Rats ◽  
Rate Of Oxygen Consumption ◽  
Spontaneously Breathing ◽  
Thermogenic Response

Background During halothane anesthesia, infants fail to increase oxygen consumption in response to a cold stimulus in the form of an increase in temperature gradient between body and environment. Based on recent observations with isolated brown-fat cells, it seemed feasible that this inability to respond could be due to an inhibition of nonshivering thermogenesis during halothane anesthesia. Methods The rate of oxygen consumption was measured in cold-acclimated hamsters and rats. The rate evoked by norepinephrine injection in hamsters at an environmental temperature of approximately 24 degrees C was used as a measure of the capacity for nonshivering thermogenesis. Anesthesia was induced by 3% halothane and maintained by 1.5% halothane. One experimental series with spontaneously breathing hamsters and a second control series with spontaneously breathing rats and with rats whose lungs were mechanically ventilated were conducted. Results Norepinephrine injection led to a fourfold increase in the rate of oxygen consumption in control hamsters; after this response had subsided, a second injection led to a similar effect. Halothane anesthesia caused an approximately 20% decrease in resting metabolic rate (P < 0.05) and a 70% inhibition of the thermogenic response to norepinephrine (P < 0.001). The halothane concentration yielding half-maximal inhibitory effect was estimated to be less than 1.0%. After the animals had recovered from halothane anesthesia, a completely restored thermogenic response to norepinephrine was observed. The inhibitory effect of halothane also was observed in hamsters maintained at normothermia and was therefore not secondary to the slight hypothermia that otherwise developed during anesthesia. In a series of control experiments, it was confirmed that rats also showed large thermogenic responses to norepinephrine injections, and it was found that, in spontaneously breathing halothane-anesthetized rats, the thermogenic response to norepinephrine was also much inhibited. Further, in halothane-anesthetized rats whose lungs were mechanically ventilated, and where blood gases were kept at virtually normal levels, the thermogenic response to norepinephrine was found to be similarly markedly inhibited. Conclusions A much diminished or abolished thermogenic response to injected norepinephrine was demonstrated in halothane-anesthetized animals. This implies that there would be a diminished ability to elicit nonshivering thermogenesis even when this process is physiologically induced. Such a diminished ability could in part explain the susceptibility of neonates and infants to hypothermia during halothane anesthesia.

scholarly journals Regulation of erythropoietin production is related to proximal tubular function

1989 ◽  
Vol 256 (5) ◽  
pp. F942-F947 ◽  
Author(s):  
K. U. Eckardt ◽  
A. Kurtz ◽  
C. Bauer
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Sensor ◽  
Collecting Duct ◽  
Inhibitory Effect ◽  
Tubular Function ◽  
Sodium Reabsorption ◽  
Renal Oxygen Consumption ◽  
Proximal Tubular ◽  
Proximal Tubular Function ◽  
Renal Oxygen

Regulation of renal erythropoietin (EPO) production is based on an intrarenal oxygen sensor. Whereas the sensitivity of this oxygen sensor to variations in renal oxygen supply is well established, the influence of changes in renal oxygen consumption has not yet been elucidated. Diuretic drugs, which inhibit active sodium reabsorption, reduce tubular oxygen consumption. We therefore investigated the effects of acetazolamide, furosemide, hydrochlorothiazide, and amiloride, known to preferentially inhibit sodium reabsorption at different segments of the nephron, on hypoxia-induced EPO formation in mice. Those drugs that are considered to act mainly in the loop of Henle, distal tubule, and collecting duct (furosemide, hydrochlorothiazide, and amiloride) did not impair EPO formation. Acetazolamide on the other hand, which is thought to act predominantly at the proximal tubular site, significantly reduced EPO formation in response to normobaric hypoxia (8 and 14% O2) and functional anemia (0.1% carbon monoxide). This inhibitory effect of acetazolamide was dose dependent and correlated with the natriuresis induced. It appeared not to depend on the metabolic acidosis induced by the drug, since the simultaneous administration of sodium bicarbonate, which restored standard bicarbonate levels to normal, did not diminish the inhibitory effect of acetazolamide on EPO production. In conclusion the data suggest that the regulation of EPO production is likely to be related to proximal tubular function.

scholarly journals The biosynthesis of intestinal mucins. The effect of salicylate on glycoprotein biosynthesis by sheep colonic and human gastric mucosal tissues in vitro

1968 ◽  
Vol 106 (3) ◽  
pp. 645-658 ◽  
Author(s):  
P W Kent ◽  
A. Allen
Keyword(s):  
Oxygen Consumption ◽  
Amino Sugar ◽  
Inhibitory Effect ◽  
Total Radioactivity ◽  
Human Gastric Mucosa ◽  
Enzyme Preparations ◽  
Acetylneuraminic Acid ◽  
Control Value ◽  
Glycoprotein Biosynthesis

1. Incubation of sheep colonic mucosal scrapings in Krebs–Ringer buffer for 2½hr. in the presence of salicylate (15mm) resulted in decreased incorporation of radioactivity into the epithelial glycoprotein from the following labelled precursors: 16·6μm-d-[2−14C]glucose (83·9% inhibition), 20μm-l-[U−14C]threonine (82%) and 35SO42−(79%). Oxygen uptake measured simultaneously was diminished to 41% of the control value. 2. At lower concentrations of salicylate (e.g. 3·75mm), incorporation of 20μm-l-[U−14C]threonine was little affected (3–6% inhibition), whereas utilization of 4μm-d-[U−14C]glucose and 35SO42− was inhibited (41–48% and 40–59% of the control values respectively). 3. Analysis of the papain-digested glycoprotein from tissue incubations with 16·6μm-d-[2−14C]glucose in the presence of salicylate (3·75mm) showed large decreases in labelling of N-acetylneuraminic acid and N-glycollylneuraminic acid residues (57% and 34% of the control values respectively) and of hexosamine constituents (glucosamine, 55% inhibition; galactosamine, 33% inhibition). Labelling of neutral sugars (galactose and fucose) was relatively little affected (9 and 11% inhibition respectively). 4. Glucose 6-phosphate transaminase and glucosamine 6-phosphate acetylase in particle-free enzyme preparations of the sheep tissue were unaffected by salicylate at the above concentrations. Acetyl-CoA synthetase was markedly inhibited. 5. Human gastric mucosa (from operation), on incubation as above, had in one experiment an oxygen consumption of 9·9μl./hr./mg. dry wt. of tissue and incorporated 5μm-d-[U−14C]glucose (15·8% of the total radioactivity added) into bound hexosamine (20·6% of the total radioactivity incorporated), hexoses (glucose and galactose, 5·7%) and fucose (14·2%). The presence of salicylate (15mm) decreased the incorporation of 5μm-d-[U−14C]glucose into the glycoprotein by 74%, all sugar constituents being affected, without influence on the rate of oxygen consumption. 6. The results suggest an inhibitory effect of salicylate on glycoprotein biosynthesis at the level of the amino sugar intermediates.

scholarly journals THE APPLICATION OF THE MATHEMATICAL MODEL FOR PREDICTING THE THRESHOLD CONCENTRATIONS OF THE INFLUENCE OF PESTICIDES ON THE SANITARY STATUS OF WATERS

2018 ◽  
Vol 97 (6) ◽  
pp. 520-524
Author(s):  
Olga S. Pivneva
Keyword(s):  
Mathematical Model ◽  
Oxygen Consumption ◽  
Experimental Studies ◽  
Oxygen Demand ◽  
Equation System ◽  
Inhibitory Effect ◽  
Water Bodies ◽  
Screening Methods ◽  
Real Risk ◽  
Biochemical Oxygen Consumption

Introduction. The rapid growth in the production and use of pesticides poses a real risk of the possible contamination of water bodies, which determines the urgency of the improving the methods of hygienic rating of pesticide preparations in water bodies, as well as the search for screening methods for establishing threshold concentrations.The issues of the need to improve the methodological approaches to the hygienic regulation of pesticide products in water of water bodies are considered, the need for further scientific study of this issue is shown. Material and methods. There are presented results of ourselves laboratory studies on the effect of herbicides of the sulfonylurea class on the processes of self-purification of reservoirs according to the Biological Oxygen Demand (BOD) index. In the work there were used substances of the sulfonylureas derivatives with a multi-directional mechanism of action that exerts both a stimulating and inhibitory effect on the course of processes of the biochemical oxygen consumption. With the use of the formula (Gotovtsev A.V., 2016), the total biochemical oxygen consumption for sulfonylurea derivatives was calculated from the two experimentally measured BOD values. Results. The data of biochemical oxygen consumption for two substances, obtained as a result of experimental studies, are presented. Selected substances have a multi-directional effect on the course of biochemical processes: stimulation - deviation of BOD from the control (%); inhibition - deviation of BOD from the control (%). There was made an estimation of the possible use of the formula for calculating the total biochemical oxygen consumption obtained in the solution of the modified Streeter-Phelps equation system for pesticides of the sulfonylurea class. The formula was applied as a mathematical model for the predictive assessment of the establishment of threshold concentrations of pesticides on the effect on the sanitary regime of water bodies (accordingly to BOD index). Discussion. In the paper, experimental and calculated values of biochemical oxygen consumption were compared, which shows the possibility of using this mathematical method for predicting the effect of pesticidal preparations of this class on the processes of self-purification of water reservoirs. Conclusion. There was shown the possibility of using mathematical modeling methods, in particular, the modified Streeter-Phelps system of equations in the practice of sanitary and hygienic investigations.

scholarly journals Hypoxia-inducible factor-1α is the therapeutic target of the SGLT2 inhibitor for diabetic nephropathy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ryoichi Bessho ◽  
Yumi Takiyama ◽  
Takao Takiyama ◽  
Hiroya Kitsunai ◽  
Yasutaka Takeda ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Oxygen Consumption ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Sglt2 Inhibitor ◽  
Inhibitory Effect ◽  
Sglt2 Inhibitors ◽  
Proximal Tubular Epithelial Cells ◽  
Renal Proximal Tubular

Abstract Previous studies have demonstrated intrarenal hypoxia in patients with diabetes. Hypoxia-inducible factor (HIF)-1 plays an important role in hypoxia-induced tubulointerstitial fibrosis. Recent clinical trials have confirmed the renoprotective action of SGLT2 inhibitors in diabetic nephropathy. We explored the effects of an SGLT2 inhibitor, luseogliflozin on HIF-1α expression in human renal proximal tubular epithelial cells (HRPTECs). Luseogliflozin significantly inhibited hypoxia-induced HIF-1α protein expression in HRPTECs. In addition, luseogliflozin inhibited hypoxia-induced the expression of the HIF-1α target genes PAI-1, VEGF, GLUT1, HK2 and PKM. Although luseogliflozin increased phosphorylated-AMP-activated protein kinase α (p-AMPKα) levels, the AMPK activator AICAR did not changed hypoxia-induced HIF-1α expression. Luseogliflozin suppressed the oxygen consumption rate in HRPTECs, and subsequently decreased hypoxia-sensitive dye, pimonidazole staining under hypoxia, suggesting that luseogliflozin promoted the degradation of HIF-1α protein by redistribution of intracellular oxygen. To confirm the inhibitory effect of luseogliflozin on hypoxia-induced HIF-1α protein in vivo, we treated male diabetic db/db mice with luseogliflozin for 8 to 16 weeks. Luseogliflozin attenuated cortical tubular HIF-1α expression, tubular injury and interstitial fibronectin in db/db mice. Together, luseogliflozin inhibits hypoxia-induced HIF-1α accumulation by suppressing mitochondrial oxygen consumption. The SGLT2 inhibitors may protect diabetic kidneys by therapeutically targeting HIF-1α protein.

scholarly journals Inhibitory Effect of Water on Oxygen Consumption by Plant Materials

1960 ◽  
Vol 35 (2) ◽  
pp. 184-188 ◽  
Author(s):  
Takao Ohmura ◽  
Robert W. Howell
Keyword(s):  
Oxygen Consumption ◽  
Inhibitory Effect ◽  
Plant Materials ◽  
Effect Of Water

Doxorubicin and epirubicin iron-induced generation of free radicals In vitro. A comparative study

1987 ◽  
Vol 7 (8) ◽  
pp. 653-658 ◽  
Author(s):  
Kjell Grankvist ◽  
Roger Henriksson
Keyword(s):  
Oxygen Consumption ◽  
Free Radicals ◽  
Myocardial Injury ◽  
Oxygen Free Radicals ◽  
Oxygen Electrode ◽  
Inhibitory Effect ◽  
Free System ◽  
A Cell ◽  
Strong Inhibitory Effect

To ascertain any differences in myocardial injury exerted by the anthracyclines doxorubicin and epirubicin, their ability to generate oxygen free radicals when mixed with Fe(II) was examined in vitro using an oxygen electrode. 5–250 μg/ml doxorubicin or epirubicin consumed oxygen when mixed with 50 or 100 μmol/1 Fe(II). Addition of 75 μmol/1 cytochrome C showed that of the consumed oxygen, approximately 80% entered the monovalent pathway of oxygen reduction. The strong inhibitory effect of 250 mg/1 catalase indicates that most of the superoxide radicals generated are further reduced to hydrogen peroxide by both anthracyclines. Addition of metal chelators DTPA (100/μmol/1), or DDTC (50 μmol/1) did not affect oxygen consumption, whereas EDTA (100/μmol/1) or desferrioxamine (100 μmol/1) with anthracyclines and Fe(II) rather stimulated oxygen consumption. It is concluded that there are no significant differences in the amount or proportion of generated oxygen free radicals between doxorubicin and epirubicin when mixed with Fe(II) in a cell-free system in vitro. Thus, the ability of the anthracyclines, in conjunction with iron alone, to generate radicals does not explain the differences of the drugs in causing myocardial injury.

Abstract 52: Enhanced Phosphodiesterase 5 (PDE5) in Thick Ascending Limbs of Dahl Salt Sensitive Rats Blunts NO-induced Inhibition of Transport

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Mohammed Z Haque ◽  
Gustavo R Ares ◽  
Pablo A Ortiz
Keyword(s):  
Oxygen Consumption ◽  
Pde5 Inhibitor ◽  
Soluble Guanylyl Cyclase ◽  
Inhibitory Effect ◽  
Thick Ascending Limb ◽  
No Donor ◽  
Cgmp Production ◽  
Pde5 Inhibition ◽  
Transport Response ◽  
Salt Sensitive Hypertension

In normal rats, NO inhibits thick ascending limb (TAL) NaCl reabsorption via cGMP. In Dahl Salt Sensitive (SS) rats NO fails to decrease TAL NaCl absorption. However, the mechanism for this defect is unknown. NO stimulates soluble guanylyl cyclase to produce cGMP. The intracellular concentrations of cGMP and its effect are limited by PDE5, a cGMP-specific phosphodiesterase. We hypothesize that enhanced PDE5 expression in SS TALs blunts the inhibitory effect of NO on transport by decreasing cGMP concentration. We isolated TALs from SS and Dahl Salt-Resistant (SR) rats fed normal salt and measured PDE5 expression by Western blot. PDE5 expression was 210±20% higher in SS TALs compared to SR ( p <0.05). We then studied whether PDE5 inhibition with vardenafil (25 nM) enhances the inhibitory effect of NO on transport by measuring Na transport-related oxygen (O 2 ) consumption in TALs. In SR TALs, the NO donor spermine-NONOate (NO) decreased O 2 consumption by 7.9±2.3% (p<0.05). Adding vardenafil to the bath further decreased O 2 consumption by 7.7±2.3% (p<0.05). In contrast, in SS TALs NO failed to decrease oxygen consumption (5±2.5% from baseline). However in the presence of a PDE5 inhibitor NO, inhibited oxygen consumption by 15.5±2.5 % (p<0.05, n=7). We then tested whether NO-stimulated cGMP production is decreased in SS TALs. To measure production, we inhibited all phosphodiesterases with IBMX. NO enhanced cGMP production in both SS and SR TALs, but production was higher in SS than SRs (delta SS: 4.0±1.0 vs SR: 1.9±0.6 fmoles/μg, p<0.05). Finally we tested whether the decreased effect of NO in SS TALs is related to enhanced cGMP degradation by PDE5. During PDE5 inhibition NO-stimulated cGMP levels were 4-fold greater in SS than SR TALs (Δ SS: 1.9±0.7 vs SR: 0.4±0.2 fmoles/μg, p<0.05). We concluded that: a) NO-induced inhibition of transport is blunted in SS TALs due to abnormally enhanced PDE5 expression and cGMP catabolism; and b) the blunted transport response to NO in SS TALs is not caused by decreased cGMP production. PDE5 inhibition in TALs could provide protection against salt-sensitive hypertension.

Comparative protection against oxyradicals by three flavonoids on cultured endothelial cells

1997 ◽  
Vol 75 (6) ◽  
pp. 717-720 ◽  
Author(s):  
Ling-Hua Zeng ◽  
Jun Wu ◽  
Beverly Fung ◽  
Jeffrey H Tong ◽  
Donald Mickle ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Oxygen Consumption ◽  
Xanthine Oxidase ◽  
Inhibitory Effect ◽  
Control Group ◽  
Aortic Endothelial Cells ◽  
Cytochrome C Reduction ◽  
Porcine Aortic Endothelial Cells ◽  
Aortic Endothelial

Oxygen-derived free radicals are known to injure the endothelium of aorta in diverse disorders. In this study we compared the cytoprotective effects of three flavonoids against oxyradical damage to porcine aortic endothelial cells in vitro. Cultured porcine aortic endothelial cells were exposed to oxyradicals generated by xanthine oxidase - hypoxanthine (XO-HP). The cytoprotective activities of morin, quercetin, and catechin on these systems were compared using established morphologic criteria. The results in the XO-HP system showed that morin at 0.125, 0.25, and 0.5 mM delayed cell necrosis to 27.4 ± 1.3, 46.8 ± 1.8, and longer than 70 min, respectively, compared with 12.0 ± 1.3 min in the control group. These degrees of protection were significantly stronger than those provided by quercetin and catechin at corresponding concentrations (p < 0.01). Morin and quercetin were moderate inhibitors of xanthine oxidase on the basis of the oxygen consumption rate, whereas catechin at the same concentrations had little inhibitory effect. The data from uric acid formation and cytochrome c reduction were consistent with the oxygen consumption measurement for the three flavonoids. Key words: flavonoids, oxyradicals, aortic endothelial cells.

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