Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ETHACRYNIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed1976

The effect of ouabain and ethacrynic acid on ATPase activities in the inner ear of the rat and guinea pig.

The effect of ethacrynic acid on ATPase activities in the stria vascularis of rat and guinea pig inner ear was studied. Both Na-K- and Mg-activated ATPase activities were inhibited non-selectively only at very high concentrations of ethacrynic acid, in contrast to the selective inhibition of Na-K-ATPase activity by ouabain. It is suggested that the deleterious effect of ethacrynic acid on the inner ear may be due to its effect on the general metabolism of the cell rather than on the ionic transport system.

Adenosine Triphosphatases↗
PubMed1993

Ethacrynic acid: outflow effects and toxicity in human trabecular meshwork in perfusion organ culture.

The effect of ethacrynic acid, a potential outflow agent for the treatment of glaucoma, was studied in a series of 25 pairs of human eyes in perfusion organ culture. Concentrations varied from 0.01 mM to 2.4 mM and were used in single or repetitive doses. Intraocular pressure was continuously recorded for up to two weeks after exposure. Eyes were then fixed and the meshwork examined histologically. Ethacrynic acid in single doses of 0.05 mM, 0.3 mM, and 0.6 mM increased facility of outflow at least 40% when compared with fellow control eyes. The duration of effect was approximately 18 hours, during which time the intraocular pressure gradually returned to baseline. Histologic examination revealed dose related effects on the trabecular cells, ranging from clumping of nuclear chromatin in some eyes to cellular swelling, disruption of cytoplasmic membranes, and cell necrosis in other eyes at concentrations of 0.1 mM and higher. No recovery or reversal of these changes was noted with time, even two weeks after a single exposure to the drug. Although ethacrynic acid is effective in temporarily lowering intraocular pressure in the human eye, a low therapeutic index may limit its clinical usefulness.

Adult↗
PubMedDate not supplied

[Role of kidney prostaglandins, kinins and dopamine receptors in the natriuretic effect of ethacrynic acid].

It was found in experiments on anesthetized rats that ethacrynic acid (3 mg/kg intravenously) exerted no effect on the blood flow in the internal zone of the cortical layer but significantly increased the blood supply to the median zone of this region of the kidneys. A pronounced natriuretic reaction produced by inhibition of this ion develops. An inhibitor of cyclooxygenase indomethacin (3 mg/kg orally, 5 days) completely eliminated an increase of the blood flow in the cortical median zone but failed to prevent an increase of diuresis and urinary excretion of sodium in response to the diuretic administration. An inhibitor of kallikrein contrykal (5000 U/kg subcutaneously) produced no effect on diuretic and natriuretic effects of the drug but prevented the hemodynamic shift in the renal cortex. A blocker of dopaminergic receptors haloperidol (3 mg/kg subcutaneously) caused no changes in the rat kidney response to ethacrynic acid. Prostaglandins and kinins formed in the kidneys under the influence of the diuretic are thought to be involved in the mechanism of dilatation of vessels of the cortical layer median zone but play no significant role in the formation of its natriuretic effect.

Absorption↗
PubMedDate not supplied

[Inhibition of chloride permeability and sodium transport in frog skin by mercusal and ethacrynic acid].

Potential difference across the frog skin is increased 1-2 min after addition of 0.063-1.0 mg/ml ethacrynic acid or 0.2-1.0 mg/ml mercusal to outside Ringer solution. Within this time the short-circuit current remains unchanged or increased. Potential difference and short-circuit current are diminished after the addition of ethacrynic acid or mercusal to inside solution. This effect is similar to that of ouabain. These findings suggest that ethacrynic acid and mercusal inhibit chloride channel in the apical cell membrane, and inhibit sodium transport in the basolateral membrane.

Animals↗
PubMed1982

The ototoxic interaction of viomycin, capreomycin and polymyxin B with ethacrynic acid.

The ototoxic interaction between the aminoglycoside antibiotics (streptomycin, kanamycin, etc.) and the loop-inhibiting diuretics (ethacrynic acid, furosemide and bumetanide) has been well documented. This interaction causes extensive destruction of the hair cells of the cochlea. Brummett et al. (1974) demonstrated that this interaction did not occur with the non-loop-inhibiting diuretics and kanamycin. The present study was undertaken to determine if antibiotics other than the aminoglycosides could produce the ototoxic interaction when combined with a loop-inhibiting diuretic. Three antibiotics-viomycin, capreomycin, and polymyxin B- when given with ethacrynic acid were found to produce cochlear hair cell damage that was similar to that produced by aminoglycoside antibiotics administered with ethacrynic acid. Therefore, the interaction appears to be specific to the loop-inhibiting diuretics but not specific for the aminoglycoside antibiotics.

Aminoglycosides↗
PubMedDate not supplied

[The binding of furosemide and ethacrynic acid with different types of biological membranes].

The study was undertaken to examine the effects of furosemide and ethacrynic acid on the fluorescence of 1,8-AHC in the suspension of erythrocytic membranes and lumenal and basolateral membranes of the rat renal epithelium. Ethacrynic acid was demonstrated to decrease probe luminescence in all three types of biological membranes. Furosemide failed to affect 1,8-AHC fluorescence in the suspension of blood ghosts and basolateral membranes of the renal epithelium and enhances probe fluorescence in the suspension of luminal membranes. The constants of binding of diuretics to the biological membranes were calculated. The effects of diuretics on the tryptophan fluorescence of renal epithelial luminal and basolateral membranes were studied in one of the series of experiments. It is suggested that the conformational rearrangements in the renal epithelial basolateral and luminal membranes can occur with ethacrynic acid. Furosemide in a dose of 10(-3) M showed the same effect only against luminal membranes.

Anilino Naphthalenesulfonates↗
PubMed1986

High-affinity binding of ethacrynic acid is mediated by the two most important drug binding sites of human serum albumin.

The binding of ethacrynic acid to human serum albumin was investigated by means of circular dichroism and equilibrium dialysis measurements, using native human serum albumin and albumin derivatives with chemical modifications impairing specifically drug binding to the indole and benzodiazepine binding site or the azapropazone-warfarin binding area, respectively. The data presented indicate that the high-affinity binding of ethacrynic acid to human serum albumin is mediated by these two important drug binding sites. Accordingly, even at relatively low concentrations ethacrynic acid displaces other drugs from both binding sites.

Apazone↗
PubMed1978

Effects of ethacrynic acid and furosemide on respiration of isolated kidney tubules: the role of ion transport and the source of metabolic energy.

In order to investigate the mechanism of action of ethacrynic acid and furosemide, experiments were designed to determine whether these drugs directly inhibit active transport or energy metabolism. The effects of these diuretics on the respiration of tubule suspensions isolated from renal cortex (of rats and rabbits) and outer medulla (of rabbits) were measured. The respiration of tubules prepared from renal outer medulla was stimulated by the presence of chloride in the incubation medium, whereas the respiration of cortical tubules was unaffected by chloride. Both ethacrynic acid and furosemide produced the greatest inhibition of respiration on tubules from outer medulla suspended in chloride-containing media; this result suggests that the diuretics directly inhibit chloride transport. The source of metabolic energy for ion transport was varied by using substrates which donate electrons to the respiratory chain at different phosphorylation sites. Both ethacrynic acid and furosemide inhibit respiration supported by beta-hydroxybutyrate, but there was little or no inhibition of respiration with succinate or tetramethylphenylenediamine ascorbate. Similarly, ouabain inhibited respiration with beta-hydroxybutyrate, but not with the other substrates. Therefore, both diuretics inhibited respiration in a fashion similar to ouabain. It is concluded from both types of experiments that ethacrynic acid and furosemide may directly inhibit active chloride transport.

Animals↗
PubMed1977

Ethacrynic acid inhibitable Ca2+ and Mg2+-activated membrane adenosine triphosphatase in rat mast cells.

A crude plasma membrane fraction from the homogenate of purified rat mast cells demonstrates a high degree of Ca2+-dependent and Mg2+-dependent adenosine triphosphatase (ATPase) activity. The microsomal and mitochondrial fractions show negligible amounts of the Ca2+ and Mg2+-activated ATPases. The broad ATPase inhibitor, ethacrynic acid, effectively blocks the mast cell ATPase activity while ouabain demonstrates little inhibitory effect. Correspondingly, ethacrynic acid inhibits histamine release from antigen-challenged mast cells while ouabain does not. Both ATPase inhibition and histamine release inhibition by ethacrynic acid require the presence of the olefinic bond in the ethacrynic acid molecule.

Adenosine Triphosphatases↗
PubMed1992

Ethacrynic acid and sulphasalazine inhibit the generation of leukotriene C4 in rat stomachs: a possible gastric anti-ulcer mechanism in cold-restraint-stressed rats.

The role of gastric glandular mucosal leukotriene C4 in gastric ulceration, produced by restraint at 4 degrees C (stress) for 2 h in rats, was studied in relation to the ulcer-preventing effects of ethacrynic acid, sulphasalazine and its constituents (sulphapyridine and 5-aminosalicylic acid), AA-861 and ONO-1078. Stress itself significantly raised mucosal leukotriene C4 levels; pretreatment with ethacrynic acid, sulphasalazine, sulphapyridine or AA-861 antagonised these changes and reduced the severity of gastric ulceration. Mucosal mast cell degranulation was prevented by ethacrynic acid, sulphasalazine, 5-aminosalicylic acid, AA-861 or ONO-1078; the mucus-depleting effect of stress was also reversed by all these drugs, except for 5-aminosalicylic acid. The anti-ulcer effect of ethacrynic acid and sulphasalazine appears to be related to their influence on glandular mucosal leukotriene C4 levels.

Animals↗
PubMed1975

Cardiac effects of ethacrynic acid, a Na+, K+-ATPase inhibitor.

To test hypotheses relating positive inotropic effects of cardiac glycosides (CG) to inhibitory effects on Na,K-ATPase, cardiac actions of other inhibitors were examined. Ethacrynic acid was studied using microelectrode recordings of dog Purkinje fibers (DP) and cat papillary muscle (CP), and isometric recordings of CP at Lmax stimulated at 1/sec (36.5 degrees C). Results with all doses (20-200 gamma/ml) were similar, differing only in latency. Actions of ethacrynic acid on electrical activity of DP and CP were, chronologically: increase in duration of the action potential (AP), and decrease in dV/dt, overshoot, and resting potential. In CP an initial increase (2-5 min) in contractility (10-15 percent) was followed by decreased in active tension and dP/dt with parallel increases in resting tension and duration of contraction. ATP levels were unchanged, eliminating the possibility of ethacrynic acid acting as a metabolic poison. Simultaneous recording of contractions and AP in CP showed that the positive inotropic effect was always associated with a lengthening of the AP. In a series of CP, ouabain (2 gamma/ml) always increased contractility when ethacrynic acid had already reduced it by 75 percent. These results suggest that Na,K-ATPase inhibition is not responsible for the inotropic effects of CG.

Action Potentials↗
PubMed1996

Inhibition of glutathione S-transferase activity in human melanoma cells by alpha,beta-unsaturated carbonyl derivatives. Effects of acrolein, cinnamaldehyde, citral, crotonaldehyde, curcumin, ethacrynic acid, and trans-2-hexenal.

The glutathione S-transferase (GST) activity towards 1-chloro-2,4-dinitrobenzene in intact human IGR-39 melanoma cells was determined by the quantification by HPLC-analysis of the excreted glutathione (GSH) conjugate (S-(2,4-dinitrophenyl)glutathione; DNPSG). The major GST subunit expressed in these melanoma cells is the pi-class GST subunit P1. Using this system, the effect of exposure for 1 h to a series of alpha, beta-unsaturated carbonyl compounds at non-toxic concentrations was studied. Curcumin was the most potent inhibitor (96% inhibition at 25 microM), while 67 and 61% inhibition at 25 microM was observed for ethacrynic acid and trans-2-hexenal, respectively. Moderate inhibition was observed for cinnamaldehyde and crotonaldehyde, while no inhibition was found for citral. The reactive acrolein did not inhibit the DNPSG-excretion at 2.5 microM, the highest non-toxic concentration. Up to about 50% GSH-depletion was found after treatment with crotonaldehyde, curcumin and ethacrynic acid, however the consequences for GST conjugation are presumably small. Reversible inhibition of GST was the major mechanism of inhibition of DNPSG-excretion in melanoma cells, except in the cases of curcumin and ethacrynic acid, which compounds also inactivated GSTP1-1 by covalent modification. This was clear from the fact that depending on the dose between 30 and 80% inhibition was still observed after lysis of the cells, under which conditions reversible inhibition was is absent. Intracellular levels of DNPSG remained relatively high in the case of ethacrynic acid. It is possible that ethacrynic acid also inhibits the transport of DNPSG by inhibition of the multidrug resistance-associated protein gene encoding glutathione conjugate export pump (MRP/GS-X pump) in some way.

Acrolein↗
PubMed1979

Quantitative relationships of the ototoxic interaction of kanamycin and ethacrynic acid.

We determined the range of doses of kanamycin sulfate and ethacrynic acid that results in an ototoxic interaction in guinea pigs. In addition, we determined the time interval between the administration of the two drugs that is needed to produce this interaction. In all cases, the magnitude of the ototoxic lesion was determined by measuring the cochlea's ability to generate both the sensitivity and intensity functions of the ac cochlear potential. In addition, the cochlear pathologic conditions, as determined by counting the number of missing hair cells in the organ of Corti, was found to correlate highly with the ac cochlear potential data. The dosage range of ethacrynic acid during which the interaction occurs is very narrow, while the dose range of kanamycin is very large.

Animals↗
PubMed1976

The effects of ouabain and ethacrynic acid on the intracellular sodium and potassium concentrations in renal medullary slices incubated in cold potassium-free ringer solution and re-incubated at 37 degrees C in the presence of external potassium.

1. The cells in slices cut from the renal outer medulla of normally hydrated adult rats were loaded with Na and depleted of K by incubation for up to 100 min in cold iso-osmolal K-free Ringer containing 180 mM-Na. There was a continuous net cellular water loss during this time; an inverse linear relationship existed between water content and intracellular Na concentration. 2. The original intracellular Na and K concentration were restored following 60 min re-incubation in warm Ringer (37 degrees C) containing 5-9 mM-K. Restoration of cellular water content was incomplete after re-incubation for up to 120 min. 3. During incubation in cold K-free Ringer the presence of 1 mM ouabain did not affect cellular Na uptake or K and water loss. Ethacrynic acid, 1 mM, completely blocked cellular Na uptake and water loss, without affecting the intracellular K concentration at 100 min. When ouabain and ethacrynic acid were present together water loss was also prevented but intracellular Na concentration rose slightly by 100 min. 4. During re-incubation in warm K-containing Ringer 1 mM ouabain inhibited Na extrusion completely for up to 60 min while only partially preventing K uptake and further depressing the level of cellular hydration. Ouabain in the presence of 1 mM ethacrynic acid had similar effects on intracellular Na and K concentrations, but raised the level of intracellular water above that of cells in control slices. 5. Ethacrynic acid alone, 1 mM, did not interfere with Na extrusion or K uptake, but also raised intracellular water above control values. 6. The results obtained are discussed in relation to (a) the nature of the preparation used, (b) the possible membrane transport processes occurring and their known or suggested sensitivity to ouabain and ethacrynic acid, (c) the mechanisms which may be responsible for cell volume maintenance in the medulla.

Animals↗
PubMedDate not supplied

The relationship between the cytotoxicity of kanamycin and ethacrynic acid for mammalian cells in vitro and their ototoxicity in vivo.

Dose-effect curves for inhibition of growth of P388/P mouse lymphoma cells by ethacrynic acid and kanamycin used alone and in combination were determined in vitro. Ethacrynic acid was 600 times more potent than kanamycin and combinations of the drugs resulted in overall additive effects. These results were compared with known dose-effect data on the ototoxicity of these drugs in vivo. Kanamycin was highly selective in its toxicity for cochlear hair cells compared to cultured cells. The dose-effect data for ethacrynic acid was coincident with that reported for functional and biochemical effects on the cochlea following perilymphatic perfusion with the drug. The potentiation observed following the ototoxic interaction the two drugs in vivo was not observed following combinations of the drugs in vitro.

Animals↗
PubMedDate not supplied

Ethacrynic acid effects on the isolated inner ear: evaluation of the ototoxic potential in an organ culture system.

The ototoxic potential of ethacrynic acid, defined as causing morphologic damage to hair cells or adjacent supporting structures, was analyzed in an organ culture model exposing inner ear structures to concentrations attainable during clinical conditions (0.1 to 10 micrograms/ml). In low doses more) ethacrynic acid caused generalized toxic effects on the tissue morphology of many types of inner ear tissues and an arrest of tissue differentiation. Although by definition ethacrynic acid is an ototoxic agent, there is, at least in the in vitro system, a very narrow dose range between the selective hair cell damaging concentration and that causing generalized toxic effects.

Animals↗
PubMed1981

Ethacrynic acid inhibits transcellular NaCl reabsorption in dog kidneys in doses of 1 to 10 mg.kg-1 and proximal bicarbonate-dependent reabsorption at higher doses.

In anesthetized dogs, sodium reabsorption in the kidney tubule was continuously reduced with increasing dosage of ethacrynic acid until 59% of the filtered load was excreted with 25 mg.kg-1 at constant glomerular filtration rate. With 50 mg.kg-1, glomerular filtration rate fell, but fractional sodium reabsorption was further reduced by 7%. In the dosage range of 1 to 10 mg.kg-1, ethacrynic acid inhibited chloride but not bicarbonate reabsorption, and the ratio between reductions in sodium reabsorption and oxygen consumption (delta Na/delta O2) averaged 25.5 +/- 5.2. With doses of 25 and 50 mg.kg-1, ethacrynic acid further reduced chloride reabsorption, reduced fractional bicarbonate reabsorption by 17% and almost halved phosphate reabsorption, whereas delta Na/delta O2 rose significantly to 65.3 +/- 12.2. Renal cortical carbonic anhydrase activity was normal and the inhibitory effect of acetazolamide, a carbonic anhydrase inhibitor, on bicarbonate reabsorption was unimpaired. We conclude that ethacrynic acid in doses up to 10 mg.kg-1 exclusively inhibits transcellular NaCl reabsorption, but in higher doses interferes with bicarbonate reabsorption and bicarbonate-dependent passive reabsorption of NaCl in the proximal tubules without inhibiting carbonic anhydrase activity.

Absorption↗