Methods for reducing oxidative stress in a cell with a sulfhydryl protected glutathione prodrug

Abstract

The present invention relates to compositions and methods for reducing oxidative stress in a cell, increasing glutathione levels in a cell, increasing L-cysteine levels in a cell and reducing hepatocytotoxicity by contacting a cell with a sulfhydryl protected glutathione prodrug or a sulfhydryl protected cysteine prodrug.

1 . A method for reducing oxidative stress in a cell of a subject comprising contacting the cell with a sulfhydryl protected glutathione prodrug so as to reduce oxidative stress in a cell.  
     
     
         2 . The method of  claim 1 , wherein oxidative stress is caused by a toxic substance, a pathogen, ultraviolet light, physical injury and/or genetic disease.  
     
     
         3 . The method of  claim 2 , wherein the toxic substance is a drug, alcohol, metal ion, ultraviolet light or radiation.  
     
     
         4 . The method of  claim 3 , wherein the drug is acetominophen, aminoglycoside antibiotic or a chemotherapeutic drug.  
     
     
         5 . CANCELLED  
     
     
         6 . CANCELLED  
     
     
         7 . The method of  claim 1 , wherein the sulfhydryl protected glutathione prodrug is L-CySSG, GSSMA, GSSME, S-Ac-GSH-OEt, a derivative thereof or a pharmaceutically acceptable salt thereof.  
     
     
         8 . CANCELLED  
     
     
         9 . A method for prolonging drug therapy by decreasing the toxicity of a drug by the method of  claim 1 .  
     
     
         10 . A method for increasing a therapeutic dosage of a drug by decreasing the toxicity of the drug by the method of  claim 1 .  
     
     
         11 - 19 . CANCELLED  
     
     
         20 . A method for increasing glutathione levels in a cell comprising administering to a subject a sulfhydryl protected glutathione prodrug so as to increase glutathione levels in a cell.  
     
     
         21 . The method of  claim 20 , wherein increasing glutathione levels reduces injury caused by an infection, cardiovascular disease, genetic disease, physical injury, ophthalmic disease, cancer, inflammation, neuropathy, acute respiratory distress syndrome (ARDS), exposure to a toxic substance, exposure to ultraviolet light, exposure to radiation and/or decreased levels of glutathione.  
     
     
         22 . The method of  claim 20 , wherein the sulfhydryl protected glutathione prodrug is L-CySSG, GSSMA, GSSME, S-Ac-GSH-OEt, a derivative thereof or a pharmaceutically acceptable salt thereof.  
     
     
         23 . CANCELLED  
     
     
         24 . CANCELLED  
     
     
         25 . A method for prolonging drug therapy by decreasing the toxicity of a drug by the method of  claim 20 .  
     
     
         26 . A method for increasing a therapeutic dosage of a drug by decreasing the toxicity of the drug by the method of  claim 20 .  
     
     
         27 - 32 . CANCELLED  
     
     
         33 . A method for increasing L-cysteine levels in a cell comprising administering to a subject a sulfhydryl protected glutathione prodrug so as to increase L-cysteine levels in a cell.  
     
     
         34 . The method of  claim 33 , wherein increasing L-cysteine levels reduces injury caused by an infection, cardiovascular disease, genetic disease, physical injury, ophthalmic disease, cancer, inflammation, neuropathy, exposure to a toxic substance, exposure to ultraviolet light, acute respiratory distress syndrome (ARDS), exposure to radiation and/or decreased levels of glutathione.  
     
     
         35 . The method of  claim 33 , wherein the sulfhydryl protected glutathione prodrug is L-CySSG, GSSMA, GSSME, S-Ac-GSH-OEt, a derivative thereof or a pharmaceutically acceptable salt thereof.  
     
     
         36 . CANCELLED  
     
     
         37 . CANCELLED  
     
     
         38 . A method for prolonging drug therapy by decreasing the toxicity of a drug by the method of  claim 33 .  
     
     
         39 . A method for increasing a therapeutic dosage of a drug by decreasing the toxicity of the drug by the method of  claim 33 .  
     
     
         40 - 45 . CANCELLED  
     
     
         46 . A method for reducing hepatotoxicity comprising administering to a subject a sulfhydryl protected glutathione prodrug so as to reduce hepatotoxicity.  
     
     
         47 . The method of  claim 46 , wherein the sulfhydryl protected glutathione prodrug is L-CySSG, GSSMA, GSSME, S-Ac-GSH-OEt, a derivative thereof or a pharmaceutically acceptable salt thereof.  
     
     
         48 . CANCELLED  
     
     
         49 . CANCELLED  
     
     
         50 . A method for prolonging drug therapy by decreasing the toxicity of a drug by the method of  claim 46 .  
     
     
         51 . A method for increasing a therapeutic dosage of a drug by decreasing the toxicity of the drug by the method of  claim 46 .  
     
     
         52 - 104 . CANCELLED