L'Hermite 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, vol.
(a) Glutathione transferase A1-1 complexed with glutathione (left) ethacrynic acid (right) conjugate (PDB code: 1GSE).
Substrate Specific activity ([micro]mol/min/mg) GST1 GST2 Ethacrynic acid
24.91 [+ or -] 1.24 15.71 [+ or -] 2.53 Hydrogen peroxide 3.93 [+ or -] 0.38 nd 1-Chloro-2,4- 0.61 [+ or -] 0.122 0.542 [+ or -] 0.127 dinitrobenzene trans, trans-Hepta-2, 0.11 [+ or -] 0.02 0.084 [+ or -] 0.01 4-dienal 1,2-Dichloro-4- Nd nd nitrobenzene p-nitrophenyl chloride Nd nd Sulfobromophthalein Nd nd trans-4-Phenyl-3- Nd nd butene-2-one Cumene hydroperoxide Nd nd Dichloromethane Nd nd nd: not detected.
The statistical analyses showed that the adult possessed the highest [I.sub50] value toward ethacrynic acid (49.54 [micro]M).
minax were shown to be inhibited by various xenobiotic compounds (ethacrynic acid, bromosulfalein, diethyl maleate, disulfiram, and curcumin), and these compounds all had greater inhibitory effects on GSTs purified from larvae, pupae and adults with [I.sub.50] at micromolar levels.
Developmental stages Effector (I50) Larva Ethacrynic acid ([micro]M) 33.3 [+ or -] 0.70 a Bromosulfalein ([micro]M) 121.6 [+ or -] 24.5 b Diethyl maleate ([micro]M) 241.5 [+ or -] 2.06 b Disulfiram ([micro]M) 57.74 [+ or -] 10.50 a Developmental stages Effector (I50) Pupa Ethacrynic acid ([micro]M) 45.9 [+ or -] 0.47 a Bromosulfalein ([micro]M) 47.5 [+ or -] 9.10 a Diethyl maleate ([micro]M) 77.8 [+ or -] 1.03 a Disulfiram ([micro]M) 205.8 [+ or -] 1.52 b Developmental stages Effector (I50) Adult Ethacrynic acid ([micro]M) 161.7 [+ or -] 5.71 b Bromosulfalein ([micro]M) 99.3 [+ or -] 21.55 b Diethyl maleate ([micro]M) 201.3 [+ or -] 4.94 b Disulfiram ([micro]M) 182.1 [+ or -] 2.28 b Each value represents the mean (M [+ or -] SE) of three replications.
Studies of tissue taken from human eyes show that ethacrynic acid doubles or triples the permeability of the trabecufar meshwork, allowing more fluid to drain from the eye, Epstein says.
The researchers tested ethacrynic acid in four men and one woman with very severe open-angle glaucoma.
"In all five patients, reduction in intraocular pressure was observed after the infection of ethacrynic acid," the team writes in the May 1992 AMERICAN JOURNAL OF OPHTHALMOLOGY.
Tetracycline Antiseptics Acetic acid Alcohol Chlorhexidine Cresylate Gentian violet Vehicles Benzalkonium chloride Polyethylene glycol Propylene glycol Salicylates Nonsteroidal anti-inflammatory drugs Quinine Chemotherapeutic drugs Carboplatinum Cisplatinum Vinblastine Vincristine Loop diuretics Ethacrynic acid
Furosemide Table 2 Agents that protect against ototoxicity Alpha lipoic acid Antioxidants Calcium Fosfomycin Glutathione Iron chelators