Mechanism of action of disulfiram and research advances in anti-glomerular basement membrane type glomerulonephritis

Abstract

Disulfiram is widely applied for treating chronic alcoholism. In recent years, researchers have proposed specific anti-cancer mechanisms by disulfiram, such as arresting the activity of acetaldehyde dehydrogenase （ALDH） and boosting intracellular reactive oxygen species （ROS）（reactive oxygen species）. A higher concentration of ROS suppressed the activity of nuclear factor kappa-B （NF-κB） and promoted the conjugation between ROS and nuclear protein localization protein 4 （nuclear protein localization protein 4）. Conjugation of NPL4, an inhibition of FROUNT protein and anti-cancer activity of disulfiram have been demonstrated in various cancer models. Anti-glomerular basement membrane glomerulonephritis is one type of acute glomerulonephritis. Upon a definite diagnosis, it should be promptly treated for relieving symptoms and improving outcomes. Disulfiram could antagonize C-C chemokine receptor type 2 and C-C chemokine receptor type 5 through suppressing C-C chemokine receptor type 2/C-C chemokine receptor type 5, CCR-2/CCR-5） and FROUNT protein interacted to suppress the migration, aggregation and activation of macrophages for alleviating anti-glomerular basement membrane type glomerulonephritis. It indicated that disulfiram had some potential therapeutic value. This review focused upon the molecular mechanism of disulfiram. And disulfiram may become a new agent for anti-glomerular basement membrane glomerulonephritis.

Keywords

• disulfiram
• anti-glomerular basement membrane glomerulonephritis
• macrophage