ethacrynic acid

Summary

Summary: A compound that inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. This compound has been classified as a loop or high ceiling diuretic.

Top Publications

  1. Habdous M, Vincent Viry M, Visvikis S, Siest G. Rapid spectrophotometric method for serum glutathione S-transferases activity. Clin Chim Acta. 2002;326:131-42 pubmed
    ..This report describes a spectrophotometric assay for monitoring the serum GST activities in human. This method will be useful in examining the relationships between serum GST activities and the GST polymorphisms, especially pi-GST. ..
  2. Aizawa S, Ookawa K, Kudo T, Asano J, Hayakari M, Tsuchida S. Characterization of cell death induced by ethacrynic acid in a human colon cancer cell line DLD-1 and suppression by N-acetyl-L-cysteine. Cancer Sci. 2003;94:886-93 pubmed
    Since ethacrynic acid (EA), an SH modifier as well as glutathione S-transferase (GST) inhibitor, has been suggested to induce apoptosis in some cell lines, its effects on a human colon cancer cell line DLD-1 were examined...
  3. Bosher S. The nature of the negative endocochlear potentials produced by anoxia and ethacrynic acid in the rat and guinea-pig. J Physiol. 1979;293:329-45 pubmed
    ..v. ethacrynic acid and after i.v. ethacrynic acid alone...
  4. Yang X, Liu G, Li H, Zhang Y, Song D, Li C, et al. Novel oxadiazole analogues derived from ethacrynic acid: design, synthesis, and structure-activity relationships in inhibiting the activity of glutathione S-transferase P1-1 and cancer cell proliferation. J Med Chem. 2010;53:1015-22 pubmed publisher
    b>Ethacrynic acid (EA) is a glutathione S-transferase P1-1 (GST P1-1) inhibitor with weak antiproliferative ability in tumor cells...
  5. Lu D, Liu J, Endo T, Zhou H, Yao S, Willert K, et al. Ethacrynic acid exhibits selective toxicity to chronic lymphocytic leukemia cells by inhibition of the Wnt/beta-catenin pathway. PLoS ONE. 2009;4:e8294 pubmed publisher
    ..The diuretic agent ethacrynic acid (EA) was identified as a Wnt inhibitor using a cell-based Wnt reporter assay...
  6. Cameron A, Sinning I, L Hermite G, Olin B, Board P, Mannervik B, et al. Structural analysis of human alpha-class glutathione transferase A1-1 in the apo-form and in complexes with ethacrynic acid and its glutathione conjugate. Structure. 1995;3:717-27 pubmed
    ..of a human alpha-class GST, isoenzyme A1-1, both in the unliganded form and in complexes with the inhibitor ethacrynic acid and its glutathione conjugate. These structures have been refined to resolutions of 2.5 A, 2.7 A and 2...
  7. Shepherd R, Martin R. Onset of ototoxicity in the cat is related to onset of auditory function. Hear Res. 1995;92:131-42 pubmed
    ..ototoxicity and auditory development, we used a single administration of Kanamycin (KA) and the loop diuretic ethacrynic acid (EA), as the co-administration of these drugs is known to produce a rapid and profound hearing loss in adult ..
  8. Rao P, Shimazaki A, Ichikawa M, Franse Carman L, Alvarado J, Epstein D. Effects of novel ethacrynic acid derivatives on human trabecular meshwork cell shape, actin cytoskeletal organization, and transcellular fluid flow. Biol Pharm Bull. 2005;28:2189-96 pubmed
    To determine efficacy and therapeutic index in the context of ocular hypotensive activity of the new ethacrynic acid (ECA) derivatives of the series (SA8,248 and SA8,389), 9,000 series (SA9,000, SA9,622 and SA9,995) and ticrynafen, we ..
  9. Wang R, Li C, Song D, Zhao G, Zhao L, Jing Y. Ethacrynic acid butyl-ester induces apoptosis in leukemia cells through a hydrogen peroxide mediated pathway independent of glutathione S-transferase P1-1 inhibition. Cancer Res. 2007;67:7856-64 pubmed
    b>Ethacrynic acid (EA), a glutathione S-transferase inhibitor and diuretic agent, inhibits cell growth and induces apoptosis in cancer cells...

More Information

Publications84

  1. Lin C, Wang Y, Challa P, Epstein D, Yuan F. Transscleral diffusion of ethacrynic acid and sodium fluorescein. Mol Vis. 2007;13:243-51 pubmed
    ..To this end, we quantified ex vivo diffusion coefficient of a potential TM drug, ethacrynic acid (ECA), and investigated mechanisms of ECA transport in the sclera...
  2. Ding D, McFadden S, Browne R, Salvi R. Late dosing with ethacrynic acid can reduce gentamicin concentration in perilymph and protect cochlear hair cells. Hear Res. 2003;185:90-6 pubmed
    A key factor in the well-known interaction between ethacrynic acid (EA) and aminoglycoside antibiotics (AABs) is disruption of the blood-labyrinth barrier (BLB), leading to rapid entry of EA and AABs into the cochlear fluids...
  3. Wang Y, Challa P, Epstein D, Yuan F. Controlled release of ethacrynic acid from poly(lactide-co-glycolide) films for glaucoma treatment. Biomaterials. 2004;25:4279-85 pubmed
    b>Ethacrynic acid (ECA) is a potential glaucoma drug that can reduce intraocular pressure. However, conventional methods of ECA administration may cause toxicity to normal eye tissues and are inconvenient to patients...
  4. Wall G, Bigner D, Craig S. Ethacrynic acid and the sulfa-sensitive patient. Arch Intern Med. 2003;163:116-7 pubmed
  5. Rhodes T, Twentyman P. A study of ethacrynic acid as a potential modifier of melphalan and cisplatin sensitivity in human lung cancer parental and drug-resistant cell lines. Br J Cancer. 1992;65:684-90 pubmed
    ..We have also investigated the effects of ethacrynic acid, a putative inhibitor of GSTs, on levels of GSH and GST activity and on cellular sensitivity to melphalan and ..
  6. Nourski K, Miller C, Hu N, Abbas P. Co-administration of kanamycin and ethacrynic acid as a deafening method for acute animal experiments. Hear Res. 2004;187:131-3 pubmed
  7. Shimazaki A, Ichikawa M, Rao P, Kirihara T, Konomi K, Epstein D, et al. Effects of the new ethacrynic acid derivative SA9000 on intraocular pressure in cats and monkeys. Biol Pharm Bull. 2004;27:1019-24 pubmed
    To evaluate the pharmacological characteristics of the new ethacrynic acid (ECA) derivative SA9000, we examined its ocular hypotensive effects in cats and cynomolgus monkeys, its corneal toxicity in rabbits, and its binding affinities ..
  8. Cynkowska G, Cynkowski T, Al Ghananeem A, Al Ghananeem A, Guo H, Ashton P, et al. Novel antiglaucoma prodrugs and codrugs of ethacrynic acid. Bioorg Med Chem Lett. 2005;15:3524-7 pubmed
    The purpose of this study was to synthesize a novel prodrug of ethacrynic acid (ECA) with short chain polyethylene glycols (PEGs) and codrugs of ECA with the beta-adrenergic blocking agent atenolol (ATL) or timolol (TML) to overcome the ..
  9. Killeen M, Englert J, Stolz D, Song M, Han Y, Delude R, et al. The phase 2 enzyme inducers ethacrynic acid, DL-sulforaphane, and oltipraz inhibit lipopolysaccharide-induced high-mobility group box 1 secretion by RAW 264.7 cells. J Pharmacol Exp Ther. 2006;316:1070-9 pubmed
    The diuretic ethacrynic acid (EA) has been shown to inhibit signaling by the proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB)...
  10. Bowes T, Gupta R. Induction of mitochondrial fusion by cysteine-alkylators ethacrynic acid and N-ethylmaleimide. J Cell Physiol. 2005;202:796-804 pubmed
    ..We previously observed that ethacrynic acid (EA) induced mitochondrial fusion in cultured BSC-1 and CHO/wt cells...
  11. Ji B, Ito K, Sekine S, Tajima A, Horie T. Ethacrynic-acid-induced glutathione depletion and oxidative stress in normal and Mrp2-deficient rat liver. Free Radic Biol Med. 2004;37:1718-29 pubmed
    ..protein (Mrp) 2, a biliary transporter involved in bile-salt-independent bile flow, under ethacrynic acid (EA)-induced acute oxidative stress...
  12. Shimazaki A, Suhara H, Ichikawa M, Matsugi T, Konomi K, Takagi Y, et al. New ethacrynic acid derivatives as potent cytoskeletal modulators in trabecular meshwork cells. Biol Pharm Bull. 2004;27:846-50 pubmed
    A series of ethacrynic acid (ECA) derivatives were synthesized and examined for ocular hypotensive activity...
  13. Ding D, Jiang H, Salvi R. Mechanisms of rapid sensory hair-cell death following co-administration of gentamicin and ethacrynic acid. Hear Res. 2010;259:16-23 pubmed publisher
    Concurrent administration of a high dose of gentamicin (GM; 125mg/kg IM) and ethacrynic acid (EA; 40mg/kg IV) results in rapid destruction of virtually all cochlear hair cells; however, the cell death signaling pathways underlying this ..
  14. Seyfried J, Soldner F, Schulz J, Klockgether T, Kovar K, Wullner U. Differential effects of L-buthionine sulfoximine and ethacrynic acid on glutathione levels and mitochondrial function in PC12 cells. Neurosci Lett. 1999;264:1-4 pubmed
    ..Direct depletion of cellular GSH using ethacrynic acid (EA, 500 mM) resulted in a concentration-dependent generation of ROI and cell death within 24 h...
  15. Rizzardini M, Lupi M, Bernasconi S, Mangolini A, Cantoni L. Mitochondrial dysfunction and death in motor neurons exposed to the glutathione-depleting agent ethacrynic acid. J Neurol Sci. 2003;207:51-8 pubmed
    ..b>Ethacrynic acid (EA) (100 microM) was added to immortalized mouse motor neurons (NSC-34) to deplete both cytosolic and ..
  16. Schmidt M, Kim Y, Gast S, Endo T, Lu D, Carson D, et al. Increased in vivo efficacy of lenalidomide and thalidomide by addition of ethacrynic acid. In Vivo. 2011;25:325-33 pubmed
    It was recently confirmed that ethacrynic acid (EA) inhibits Wnt/beta catenin signalling in myeloma. This study investigated the antitumor effect of EA in vitro and in vivo in a murine myeloma model...
  17. Lin C, Yuan F. Numerical simulations of ethacrynic acid transport from precorneal region to trabecular meshwork. Ann Biomed Eng. 2010;38:935-44 pubmed publisher
    ..the drug delivery, a mathematical model was developed to numerically simulate the transport process of ethacrynic acid (ECA), a potential drug for glaucoma treatment, in the anterior segment of a typical human eye...
  18. Han Y, Englert J, Delude R, Fink M. Ethacrynic acid inhibits multiple steps in the NF-kappaB signaling pathway. Shock. 2005;23:45-53 pubmed
    b>Ethacrynic acid has been used as a safe and effective diuretic for more than 30 years...
  19. Su Y, Chiang L, Jeng K, Huang H, Chen J, Lin W, et al. Solution-phase parallel synthesis and screening of anti-tumor activities from fenbufen and ethacrynic acid libraries. Bioorg Med Chem Lett. 2011;21:1320-4 pubmed publisher
    The derivatives with fenbufen and ethacrynic acid core compounds was synthesized through a facial preparation of 1-amino-4-azidobutane. The subsequent coupling with 102 members of carboxylic acids afforded amide products...
  20. Jin G, Lu D, Yao S, Wu C, Liu J, Carson D, et al. Amide derivatives of ethacrynic acid: synthesis and evaluation as antagonists of Wnt/beta-catenin signaling and CLL cell survival. Bioorg Med Chem Lett. 2009;19:606-9 pubmed publisher
    A series of amides of ethacrynic acid was prepared and evaluated for their ability to inhibit Wnt signaling and decrease the survival of CLL cells. Several of the most potent derivatives were active in the low micromolar range...
  21. Li R, El Mallakh R. Differential response of bipolar and normal control lymphoblastoid cell sodium pump to ethacrynic acid. J Affect Disord. 2004;80:11-7 pubmed
    ..Previous work has demonstrated a reduced adaptive response of the sodium pump to ethacrynic acid in lymphocytes obtained from bipolar subjects compared to psychiatrically normal controls...
  22. Zaman G, Cnubben N, van Bladeren P, Evers R, Borst P. Transport of the glutathione conjugate of ethacrynic acid by the human multidrug resistance protein MRP. FEBS Lett. 1996;391:126-30 pubmed
    ..In this study we demonstrate that the glutathione S-conjugate of the diuretic drug ethacrynic acid, which is an efficient inhibitor of glutathione S-transferases, is a high-affinity substrate and inhibitor of ..
  23. Wang R, Liu C, Xia L, Zhao G, Gabrilove J, Waxman S, et al. Ethacrynic acid and a derivative enhance apoptosis in arsenic trioxide-treated myeloid leukemia and lymphoma cells: the role of glutathione S-transferase p1-1. Clin Cancer Res. 2012;18:6690-701 pubmed publisher
    ..We tested whether a combination with ethacrynic acid (EA), a glutathione S-transferase P1-1 (GSTP1-1) inhibitor, and a reactive oxygen species (ROS) inducer will ..
  24. Iersel M, Ploemen J, Struik I, van Amersfoort C, Keyzer A, Schefferlie J, et al. 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. Chem Biol Interact. 1996;102:117-32 pubmed
    ..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...
  25. Na Y, Han K, Park H, Yang E. Menadione and ethacrynic acid inhibit the hypoxia-inducible factor (HIF) pathway by disrupting HIF-1? interaction with p300. Biochem Biophys Res Commun. 2013;434:879-84 pubmed publisher
    ..Two small molecule inhibitors, menadione (MD) and ethacrynic acid (EA), were found to decrease expression of luciferase under the control of hypoxia-responsive elements in ..
  26. Ding D, Jiang H, Wang P, Salvi R. Cell death after co-administration of cisplatin and ethacrynic acid. Hear Res. 2007;226:129-39 pubmed
    b>Ethacrynic acid (EA) significantly enhances the ototoxic effects of cisplatin. To gain insights into the mechanisms underlying Cis/EA ototoxicity, cochleas were labeled with several apoptotic markers...
  27. Yamamoto K, Masubuchi Y, Narimatsu S, Kobayashi S, Horie T. Toxicity of ethacrynic acid in isolated rat hepatocytes. Toxicol In Vitro. 2002;16:151-8 pubmed
    b>Ethacrynic acid, a loop diuretic drug, caused lipid peroxidation in isolated rat hepatocytes...
  28. Walker R, O Brien E, Epstein D, Sheetz M. n-ethylmaleimide and ethacrynic acid inhibit kinesin binding to microtubules in a motility assay. Cell Motil Cytoskeleton. 1997;37:289-99 pubmed
    ..microtubule (MT) motor kinesin, the motor was treated with two SH reactive compounds, n-ethylmaleimide and ethacrynic acid, and its function was assayed by motility and co-sedimentation techniques...
  29. Oakley A, Rossjohn J, Lo Bello M, Caccuri A, Federici G, Parker M. The three-dimensional structure of the human Pi class glutathione transferase P1-1 in complex with the inhibitor ethacrynic acid and its glutathione conjugate. Biochemistry. 1997;36:576-85 pubmed
    The potent diuretic drug ethacrynic acid has been tested in clinical trials as an adjuvant in chemotherapy. Its target is the detoxifying enzyme glutathione transferase which is often found overexpressed in cancer tissues...
  30. Shamblin S, Hancock B, Pikal M. Coupling between chemical reactivity and structural relaxation in pharmaceutical glasses. Pharm Res. 2006;23:2254-68 pubmed
  31. Kulkarni A, Sajan M. Lipoxygenase-another pathway for glutathione conjugation of xenobiotics: A study with human term placental lipoxygenase and ethacrynic acid. Arch Biochem Biophys. 1999;371:220-7 pubmed
    ..ability of human term placental lipoxygenase (HTPLO) to catalyze glutathione (GSH) conjugate formation from ethacrynic acid (EA) in the presence of linoleic acid (LA) and GSH...
  32. Valdez B, Hassan M, Andersson B. Development of an assay for cellular efflux of pharmaceutically active agents and its relevance to understanding drug interactions. Exp Hematol. 2017;52:65-71 pubmed publisher
    ..We demonstrated that chlorambucil, 4-hydroperoxycyclophosphamide, ketoconazole, ethacrynic acid, everolimus, and sirolimus strongly inhibited 5-CF efflux in lymphoma and leukemia cell lines...
  33. Setlíková I, Wiegand C. Hepatic and branchial glutathione S-transferases of two fish species: substrate specificity and biotransformation of microcystin-LR. Comp Biochem Physiol C Toxicol Pharmacol. 2009;149:515-23 pubmed publisher
    ..for 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), 4-nitrobenzyl chloride (pNBC) and ethacrynic acid (ETHA). Biotransformation rate of MC-LR was determined by high performance liquid chromatography (HPLC)...
  34. Rodríguez M, Bisset J, Fernández D. [Determination in vivo of the role of esterase and glutathione transferase enzymes in pyrethroid resistance of Aedes aegypti (Diptera: Culicidae)]. Rev Cubana Med Trop. 2007;59:209-12 pubmed
    An in vivo study of two synergists, that is, Triphenil phosphate -specific esterase inhibitor- and ethacrynic acid -specific gluthation transferase inhibitor- was performed to determine if these enzymes were responsible for pyrethroid ..
  35. Perregaux D, Bhavsar K, Contillo L, Shi J, Gabel C. Antimicrobial peptides initiate IL-1 beta posttranslational processing: a novel role beyond innate immunity. J Immunol. 2002;168:3024-32 pubmed
    ..Thus, both processes were disrupted by a caspase inhibitor, both were sensitive to ethacrynic acid and CP-424,174, two pharmacological agents that suppress posttranslational processing, and both were negated ..
  36. Raphael Y, Kim Y, Osumi Y, Izumikawa M. Non-sensory cells in the deafened organ of Corti: approaches for repair. Int J Dev Biol. 2007;51:649-54 pubmed
    ..The mitotic potential of these cells should facilitate production of cells for therapies based on recapitulation of development or insertion of stem cells...
  37. Vivas L, Chiaraviglio E. Central effect of agents which alter sodium transport on water drinking in the rat. Brain Res Bull. 1989;22:201-6 pubmed
    The central effect of ouabain (OUA), ethacrynic acid (EA) and diphenylhydantoin (DPH) on water drinking was studied in rats...
  38. Messina C, Weiher H, Schmidt Wolf I. Targeting Prostate Cancer with a Combination of WNT Inhibitors and a Bi-functional Peptide. Anticancer Res. 2017;37:555-559 pubmed
    ..Two different WNT inhibitors were used, ethacrynic acid and ciclopiroxolamine. They were tested on prostate cancer cells using the WST-8 assay...
  39. Dia A, Guèye O, Niang E, Diédhiou S, Sy M, Konaté A, et al. Insecticide resistance in Anopheles arabiensis populations from Dakar and its suburbs: role of target site and metabolic resistance mechanisms. Malar J. 2018;17:116 pubmed publisher
    ..arabiensis populations for a suitable insecticide resistance management system to preserve core insecticide-based vector control tools in this flooded area. ..
  40. Donham R, Morin D, Tjeerdema R. Salinity effects on activity and expression of glutathione S-transferases in white sturgeon and Chinook salmon. Ecotoxicol Environ Saf. 2006;63:293-8 pubmed
    ..174; n = 10). GST activity of both sturgeon and salmon toward ethacrynic acid (ETHA) did not significantly change with elevated salinity (P = 0.516 with n = 3, and P = 0...
  41. Garg G, Cho C, Ogle C. Ethacrynic acid and sulphasalazine inhibit the generation of leukotriene C4 in rat stomachs: a possible gastric anti-ulcer mechanism in cold-restraint-stressed rats. Pharmacology. 1992;44:177-89 pubmed
    ..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...
  42. Myzak M, Karplus P, Chung F, Dashwood R. A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase. Cancer Res. 2004;64:5767-74 pubmed
    ..Collectively, these findings suggest that SFN may be effective as a tumor-suppressing agent and as a chemotherapeutic agent, alone or in combination with other HDAC inhibitors currently undergoing clinical trials. ..
  43. Bryant Z, Janser R, Jabarkhail M, Candelaria Lyons M, Romero B, Van Slambrouck S, et al. Inhibitory effects of ethacrynic acid analogues lacking the ?,?-unsaturated carbonyl unit and para-acylated phenols on human cancer cells. Bioorg Med Chem Lett. 2011;21:912-5 pubmed publisher
    A series of ethacrynic acid analogues, lacking the ?,?-unsaturated carbonyl unit, was synthesized and subsequently evaluated for their ability to inhibit the migration of human breast cancer cells, Hs578Ts(i)8 as well as of human ..
  44. Mockus L, Paul T, Pease N, Harper N, Basu P, Oslos E, et al. Quality by design in formulation and process development for a freeze-dried, small molecule parenteral product: a case study. Pharm Dev Technol. 2011;16:549-76 pubmed publisher
    ..The process design space is constructed to take into account limitations on the process imposed by the product and by equipment capability. ..
  45. Xia S, Feng C, Guo A. Multiple-phase model of memory consolidation confirmed by behavioral and pharmacological analyses of operant conditioning in Drosophila. Pharmacol Biochem Behav. 1998;60:809-16 pubmed
    ..min after training, and susceptible to disruption by the ATPase deactivating chemicals such as ouabain and ethacrynic acid (EA)...
  46. Colpaert E, Timmermans J, Lefebvre R. Influence of antioxidant depletion on nitrergic relaxation in the pig gastric fundus. Br J Pharmacol. 2002;135:917-26 pubmed
    ..5. Pharmacological depletion studies, corroborated by immunohistochemical data, thus suggest a role for Cu/Zn SOD but not for GSH in nitrergic neurotransmission in the porcine gastric fundus. ..
  47. Willett K, Gardinali P, Lienesch L, Di Giulio R. Comparative metabolism and excretion of benzo(a)pyrene in 2 species of ictalurid catfish. Toxicol Sci. 2000;58:68-76 pubmed
    ..BaP treatment had no significant effect on cytosolic 1-chloro-2,4-dinitrobenzene or ethacrynic acid (EA)-glutathione-S:- transferase (GST) and cis-stilbene oxide-microsomal epoxide hydrolase (EH) activities of ..
  48. McFadden S, Ding D, Jiang H, Woo J, Salvi R. Chinchilla models of selective cochlear hair cell loss. Hear Res. 2002;174:230-8 pubmed
    Although it is well known that ethacrynic acid (EA) can enhance gentamicin (GM) ototoxicity, there has been no systematic study of the relationship between dosing parameters and inner ear pathology...
  49. Yamasoba T, Kondo K, Miyajima C, Suzuki M. Changes in cell proliferation in rat and guinea pig cochlea after aminoglycoside-induced damage. Neurosci Lett. 2003;347:171-4 pubmed
    ..cochleae of guinea pigs and rats was investigated after systemic application of kanamycin sulfate (KM) and ethacrynic acid (EA)...
  50. Mukanganyama S, Widersten M, Naik Y, Mannervik B, Hasler J. Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer. 2002;97:700-5 pubmed
    ..Using the substrate ethacrynic acid, a diuretic drug also used as a modulator to overcome drug resistance in tumour cells, GST P1-1 activity was ..
  51. Zhang N, Jin G, Jin Z, Liu B, Peng B, Gao N, et al. [Combination of TLR7 agonist T7-ethacrynic acid conjugate with ROR1 has a stronger anti-breast cancer effect]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016;32:876-80 pubmed
    Objective To investigate the synergistic anti-breast cancer effect of Toll-like receptor 7 agonist T7-ethacrynic acid conjugate (T7-EA) in combination with receptor-tyrosine-kinase-like orphan receptor 1 (ROR1)...
  52. Qin G, Jia M, Liu T, Zhang X, Guo Y, Zhu K, et al. Characterization and functional analysis of four glutathione S-transferases from the migratory locust, Locusta migratoria. PLoS ONE. 2013;8:e58410 pubmed publisher
    ..The optimal pH of the locust GSTs ranged between 7.0 to 9.0. Ethacrynic acid and reactive blue effectively inhibited all four GSTs...
  53. Labrou N, Kotzia G, Clonis Y. Engineering the xenobiotic substrate specificity of maize glutathione S-transferase I. Protein Eng Des Sel. 2004;17:741-8 pubmed
    ..Thermodynamic analysis of the activity data showed that the activation energy increases at low temperatures, whereas the entropy change seems to be the main determinant that contributes to the rate-limiting step at high temperatures. ..
  54. Bowes T, Gupta R. Novel mitochondrial extensions provide evidence for a link between microtubule-directed movement and mitochondrial fission. Biochem Biophys Res Commun. 2008;376:40-5 pubmed publisher
    ..Previously, we reported that treatment of mammalian cells with the cysteine-alkylators, N-ethylmaleimide and ethacrynic acid, induced rapid mitochondrial fusion forming a large reticulum approximately 30 min after treatment...
  55. Beal A. The effect of transport-blocking drugs on secretion of fluid and electrolytes by the mandibular gland of red kangaroos, Macropus rufus. Arch Oral Biol. 1997;42:705-16 pubmed
    ..No evidence was found for fluid secretion being dependent on Cl transport involving Na/H and Cl/HCO3 antiports or on HCO3 synthesis involving carbonic anhydrase. ..
  56. McFadden S, Ding D, Jiang H, Salvi R. Time course of efferent fiber and spiral ganglion cell degeneration following complete hair cell loss in the chinchilla. Brain Res. 2004;997:40-51 pubmed
    b>Ethacrynic acid (EA) is known to interact with aminoglycoside antibiotics such as gentamicin (GM)...
  57. Frey H. Antiepileptic effect of loop diuretics? Comment to "Differential effects of cation-chloride co-transport-blocking diuretics in a rat hippocampal slice model of epilepsy" by Margineanu, Klitgaard, Epilepsy Res. 69 (2006) 93-99. Epilepsy Res. 2006;71:237-8; author reply 239-40 pubmed
  58. Reid K, Guo S, Iyer V. Agents which block potassium-chloride cotransport prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. Brain Res. 2000;864:134-7 pubmed
    The purpose of this study was to determine whether the loop diuretics furosemide, bumetanide and ethacrynic acid, which block the KCC1 potassium-chloride transporter in the kidney loop of Henle and the KCC2 potassium-chloride transporter ..
  59. Lin C, Gonzalez P, Yuan F. Cellular pharmacokinetic and pharmacodynamic analyses of ethacrynic acid: Implications in topical drug delivery in the eye. Mol Vis. 2011;17:2507-15 pubmed
    b>Ethacrynic acid (ECA) is a potential trabecular meshwork (TM) drug that has shown promising results in preclinical studies for treatment of primary open-angle glaucoma...
  60. Blackburn A, Tzeng H, Anders M, Board P. Discovery of a functional polymorphism in human glutathione transferase zeta by expressed sequence tag database analysis. Pharmacogenetics. 2000;10:49-57 pubmed
    ..6-fold higher activity towards dichloroacetate. This report demonstrates the discovery of a functional polymorphism by analysis of the EST database. ..
  61. Quesada Soriano I, Parker L, Primavera A, Wielens J, Holien J, Casas Solvas J, et al. Diuretic drug binding to human glutathione transferase P1-1: potential role of Cys-101 revealed in the double mutant C47S/Y108V. J Mol Recognit. 2011;24:220-34 pubmed publisher
    The diuretic drug ethacrynic acid (EA), both an inhibitor and substrate of pi class glutathione S-transferase (GST P1-1), has been tested in clinical trials as an adjuvant in chemotherapy...
  62. Smee D, Hurst B, Wong M. Lack of efficacy of aurintricarboxylic acid and ethacrynic acid against vaccinia virus respiratory infections in mice. Antivir Chem Chemother. 2010;20:201-5 pubmed publisher
    Aurintricarboxylic acid (ATA) and ethacrynic acid (ECA) have been reported to exhibit antiviral activity against vaccinia virus infections in cell culture by inhibiting early and late gene transcription, respectively...
  63. Khera S, Grillo M, Schnier P, Hollis S. Application of diffusion-edited NMR spectroscopy for the structural characterization of drug metabolites in mixtures. J Pharm Biomed Anal. 2010;51:164-9 pubmed publisher
    ..1)H, 1D NOESY-presaturation, and 1D diffusion-edited experiments run on 20 microg and 100 microg samples of ethacrynic acid glutathione thioether (EASG) and a previously unreported metabolite of mefenamic acid, mefenamic acid ..
  64. Zhan Y, Rule G. Glutathione induces helical formation in the carboxy terminus of human glutathione transferase A1-1. Biochemistry. 2004;43:7244-54 pubmed
    ..Addition of either GSH or the conjugate between GSH and ethacrynic acid (EASG) causes this segment to become a stable alpha-helix...
  65. Rejali D, Lee V, Abrashkin K, Humayun N, Swiderski D, Raphael Y. Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons. Hear Res. 2007;228:180-7 pubmed
    ..This protective effect decreased in the higher cochlear turns. The data demonstrate the feasibility of combining cochlear implant therapy with ex vivo gene transfer for enhancing spiral ganglion neuron survival. ..
  66. Ergun Y, Ogulener N. Selective modifiers of glutathione prevent restoration of photorelaxations in mouse gastric fundus. Fundam Clin Pharmacol. 2005;19:503-9 pubmed
    ..The second series of photorelaxations attenuated statistically when compared with those in the first series. Ethacrynic acid (1 microm), diamide (1 microm) and glutathione (1 microm) had no effect on the photorelaxations occurred in ..
  67. Slim H, Black H, Thompson P. Older blood pressure medications-do they still have a place?. Am J Cardiol. 2011;108:308-16 pubmed publisher
    ..drugs: sympatholytic agents such as reserpine, methyldopa, and clonidine; diuretics such as chlorthalidone, ethacrynic acid and spironolactone; the vasodilators hydralazine and minoxidil; and others...
  68. Perez Cornejo P, Arreola J, Law F, Schultz J, Knauf P. Volume-sensitive chloride channels do not mediate activation-induced chloride efflux in human neutrophils. J Immunol. 2004;172:6988-93 pubmed
    ..the number and affinity of beta(2) integrin surface adhesion molecules (up-regulation) are all inhibited by ethacrynic acid and certain aminomethyl phenols...
  69. Cuccarolo P, Viaggi S, Degan P. New insights into redox response modulation in Fanconi's anemia cells by hydrogen peroxide and glutathione depletors. FEBS J. 2012;279:2479-94 pubmed publisher
    ..Among the various GSH inhibitors employed, FA cells appear particularly resistant to menadione (5 ?m) and ethacrynic acid (ETA, 50 ?m), two drugs that specifically target mitochondria...
  70. Meredith M, Allman B. Early hearing-impairment results in crossmodal reorganization of ferret core auditory cortex. Neural Plast. 2012;2012:601591 pubmed publisher
    ..These data, along with similar observations from adult-deafened and adult hearing-impaired animals, support the recently proposed brainstem theory for crossmodal plasticity induced by hearing loss. ..
  71. Jozkowicz A, Was H, Taha H, Kotlinowski J, Mleczko K, Cisowski J, et al. 15d-PGJ2 upregulates synthesis of IL-8 in endothelial cells through induction of oxidative stress. Antioxid Redox Signal. 2008;10:2035-46 pubmed publisher
    ..In summary, we showed that 15d-PGJ(2), acting through oxidative stress, may exert proinflammatory effects. The upregulation of IL-8 is mostly associated with p38-mediated stabilization of mRNA. ..
  72. Triguero D, González Herreros M, Costa G, Garcia Pascual A. Localization and thiol dependancy of endogenous nitro compounds-mediating urethral photo-relaxation. Pflugers Arch. 2008;455:745-56 pubmed
    ..Moreover, when the mitochondrial pool was effectively reduced by incubation with ethacrynic acid, the responses to LS were further reduced until they disappeared after intensive LS...
  73. Shimazaki A, Kirihara T, Rao P, Tajima H, Matsugi T, Epstein D. Effects of the new ethacrynic acid oxime derivative SA12590 on intraocular pressure in cats and monkeys. Biol Pharm Bull. 2007;30:1445-9 pubmed
    To evaluate the pharmacological characteristics of SA12590, a new oxime-derivative of the ethacrynic acid (ECA) derivative SA9000, we examined both its ocular hypotensive effects (in ocular normotensive cats and cynomolgus monkeys) and ..
  74. Yu H, Klonowski Stumpe H. Ethacrynic acid inhibits pancreatic exocrine secretion. Acta Pharmacol Sin. 2001;22:961-5 pubmed
    The effect of ethacrynic acid on pancreatic exocrine secretion function and potential mechanisms of interference with the secretory process in pancreatic acinar cells were investigated...
  75. Richardson K, Gold Bouchot G, Schlenk D. The characterization of cytosolic glutathione transferase from four species of sea turtles: loggerhead (Caretta caretta), green (Chelonia mydas), olive ridley (Lepidochelys olivacea), and hawksbill (Eretmochelys imbricata). Comp Biochem Physiol C Toxicol Pharmacol. 2009;150:279-84 pubmed publisher
    ..GST from the herbivorous green sea turtle shows 3 fold higher activity with the substrate ethacrynic acid than the carnivorous olive ridley sea turtle...