Cellular and Biochemical Alterations Caused by Artificial Depletion of Glutathione

N.   Tolosa de   Talamoni; A.      Marchionatti; G.   Diaz de   Barboza; A.      Perez

Abstract

This review will focus on glutathione depletion performed in different biological systems to elucidate molecular implications of this tripeptide on physiological and pathological processes. Cellular and molecular changes produced in liver, brain and kidney by glutathione depleting drugs, such as D,Lbuthionine- S,R-sulfoximine, menadione and acetaminophen, will be described. Special attention will be given to the inhibitory mechanisms produced by those drugs on intestinal calcium absorption and alkaline phosphatase activity. The role of DL-buthionine-S,R-sulfoximine and menadione on mechanisms of apoptosis, reactive oxygen species production and mitochondrial function from mammalian breast cancer cells will be analyzed. Finally, reversion or prevention of some of the previous effects by administration of lipoic acid, glutathione monoester, KR31378 and 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid will be discussed.

Keywords: glutathione, menadione, buthionine, sulfoximine, acetominophen, vitamin d, mcf cells, enterocytes, glutathione monoester, calcium absorption