Possible Interaction: Ethacrynic Acid and Glutathione

“ Ethacrynic acid inhibits the isoenzymes of GSH transferase with 50% inhibitory concentration values ranging from 0.3 to 6.0 microM and has been shown to restore sensitivity to alkylating agents in drug-resistant animal tumor models.”

“RESULTS The results revealed that EA (0.01-10 μM) significantly increased cell proliferation and GSH level, while decreased the levels of ROS, MDA, TNF-α, β-GAL and AGEs following DG-induced aging.”

“It is known that ethacrynic acid (EA) decreases the intracellular levels of glutathione.”

“ Glutathione (GSH) levels were dose-dependently increased in cells treated with EA and this increase was hardly affected by NAC addition.”

“This implies that ethacrynic acid may modulate drug resistance of tumor cells not only by inhibiting glutathione S-transferase activity, but also by inhibiting the export of drug conjugates from the cell by MRP.”

“ EA pretreatment resulted in a marked GSH depletion as well as GST activity inhibition in both of these cells.”

“Treatments with PNBC, IDM, and EA decreased GSH contents in guard cells.”

“Herein we show that ethacrynic acid EA ), which is able to increase cellular oxidative stress through glutathione depletion , induces TDP-43 C-terminal phosphorylation at serine 403/404 and 409/410, insolubilization, C-terminal fragmentation, and cytoplasmic distribution in NSC34 cells and primary cortical neurons.”

“In addition, glutathione (1 microm) reversed the prevention achieved by ethacrynic acid and diamide.”

“Diethyl maleate, ethacrynic acid and buthionine sulfoximine, three agents which significantly reduce glutathione levels , also decreased 99mTc-HMPAO retention in both astrocytes and in neurons.”