The Relevance of Glutathione Reductase Inhibition by Fluoxetine to Human Health and Disease: Insights Derived from a Combined Kinetic and Docking Study.

Glutathione reductase (GR) is a homodimeric enzyme playing an important role in the regeneration of the central antioxidant molecule reduced glutathione (GSH) from oxidized glutathione (GSSG) at the expense of a molecule of NADPH. GSH scavenges and eliminates superoxide and hydroxyl radicals non-enzymatically or serves as an electron donor for several enzymes. Fluoxetine (FLU), a selective serotonin reuptake inhibitor, is widely prescribed in the treatment of major depressive disorder.

Computational and experimental studies on the interaction between butyrylcholinesterase and fluoxetine: implications in health and disease.

Butyrylcholinesterase (BChE) is a serine esterase that plays a role in the detoxification of natural as well as synthetic ester-bond-containing compounds. Alterations in BChE activity are associated with a number of diseases. Cholinergic system abnormalities in particular are correlated with the formation of senile plaques in Alzheimer's disease (AD), and administration of cholinesterase inhibitors is a common therapeutic approach used to treat AD.

Purification of Glutathione S-Transferase pi from Erythrocytes and Evaluation of the Inhibitory Effect of Hypericin.

Hypericin is a photosensitizer compound used in the photodynamic therapy (PDT). PDT is an alternative cancer treatment strategy whose function is dependent on the photosensitizers accumulating selectively in tumor cells and following visible or infra-red light induced activation lead to the apoptosis/necrosis of the tumor cells via the formation of reactive oxygen species. Thus, the cellular redox balance is essential for the efficacy of PDT.

Amitriptyline may have a supportive role in cancer treatment by inhibiting glutathione S-transferase pi (GST-π) and alpha (GST-α).

A tricyclic anti-depressant, amitriptyline, is a highly prescribed drug for cancer patients for mood elevation but there are limited studies about the interaction of amitriptyline with glutathione S-transferases pi (GST-π) and glutathione S-transferases alpha (GST-α). GST isozymes have been implicated in chemotherapeutic drug resistance. We demonstrated that the concentration dependent inhibition of GST-π and GST-α by amitriptyline followed inverse hyperbolic inhibition curves with IC(50) values of 5.

Inhibition characteristics of hypericin on rat small intestine glutathione-S-transferases.

Glutathione-S-transferases constitute a family of enzymes involving in the detoxification of xenobiotics, signalling cascades and serving as ligandins or/and catalyzing the conjugation of various chemicals and drugs. The widely expressed cytosolic GST-pi is a marker protein in various cancers and its increased concentration is linked to drug resistance. GST-pi is autoregulated by S-glutathionylation and it catalyzes the S-glutathionylation of other proteins in response to oxidative or nitrosative stress.