Altering expression level of glutathione s-transferase genes by treating a human subject with a nitroxide

Abstract

A method of treatment is disclosed. The method comprises administering to a human subject, known to have decreased glutathione activity, an effective amount of a nitroxide antioxidant, wherein the nitroxide antioxidant increases an expression level of one or more genes encoding glutathione S-transferase enzymes, thereby increasing glutathione activity.

1 . A method of upregulating an expression level of one or more glutathione S-transferase (GST) genes, the method comprising:
 administering an effective amount of a nitroxide antioxidant to an individual known to have or suspected to have oxidative stress, whereby the expression level of at least one gene encoding the GST gene is upregulated,   the oxidative stress caused by a disease or condition selected from the group consisting of lung disease, lung injury, liver fibrosis, liver disease or injury, viral infection, bacterial infection, intraocular melanoma, ataxia, and ischemia-reperfusion injury.   
     
     
         2 . (canceled) 
     
     
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         5 . The method of  claim 1 , wherein the at least one gene is selected from a group consisting of Gstm3, Gstm6, Gsta3, Gstt1, Gsta4, Gstm1, Gstm4, Gstt2, Gstp1, and Gstk1. 
     
     
         6 . A method for increasing the expression level of a gene in a human subject in need thereof, comprising:
 identifying a human subject having a decreased expression level of a gene associated with glutathione S-transferase (GST) activity, wherein the gene is selected from the group consisting of Gstm3, Gstm6, Gsta3, Gstt1, Gsta4, Gstm1, Gstm4, Gstt2, Gstp1, and Gstk1; and   administering to the human subject an effective amount of a nitroxide antioxidant to increase the level of expression of the gene associated with the GST activity.   
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . A method for increasing an expression level, in a eukaryotic cell, of one or more genes encoding one or more GST enzymes by administering a nitroxide antioxidant to eukaryotic cell. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . A method for treating or preventing xenobiotic induced oxidative stress comprising:
 administering an effective amount of a nitroxide antioxidant to an individual having xenobiotic induced oxidative stress, whereby an expression level of one or more GST genes is upregulated.   
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the nitroxide antioxidant is selected from the group consisting of 2-ethyl-2,5,5-trimethyl-3-oxazolidine-1-oxyl (OXANO), 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), 4-amino-2,2,6,6-tetramethyl-1-piperidinyloxy (Tempamine), 3-Aminomethyl-PROXYL, 3-Cyano-PROXYL, 3-Carbamoyl-PROXYL, 3-Carboxy-PROXYL, 4-Oxo-TEMPO, 4-amino-TEMPO, 4-(2-bromoacetamido)-TEMPO, 4-ethoxyfluorophosphonyloxy-TEMPO, 4-hydroxy-TEMPO, 4-(2-iodoacetamido)-TEMPO, 4-isothiocyanato-TEMPO, 4-maleimido-TEMPO, 4-(4-nitrobenzoyloxyl)-TEMPO, or 4-phosphonooxy-TEMPO. 
     
     
         22 . The method of  claim 21 , wherein the GST gene is selected from the group consisting of Gstm3, Gstm6, Gsta3, Gstt1, Gsta4, Gstm1, Gstm4, Gstt2, Gstp1, and Gstk1. 
     
     
         23 . The method of  claim 21 , wherein the nitroxide antioxidant is 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL). 
     
     
         24 . The method of  claim 21 , further comprising administering to the individual to a xenobiotic prior to administering to the individual the effective amount of the nitroxide antioxidant. 
     
     
         25 . The method of  claim 21 , wherein the effective amount is from 0.01 mg/kg to 300 mg/kg. 
     
     
         26 . The method of  claim 21 , wherein the oxidative stress caused by lung disease. 
     
     
         27 . The method of  claim 21 , wherein the oxidative stress caused by liver fibrosis. 
     
     
         28 . The method of  claim 21 , wherein the oxidative stress caused by liver disease or injury. 
     
     
         29 . The method of  claim 21 , wherein the oxidative stress caused by inflammatory bowel disease viral infection. 
     
     
         30 . The method of  claim 21 , wherein the oxidative stress caused by bacterial infection. 
     
     
         31 . The method of  claim 21 , wherein the oxidative stress caused by intraocular melanoma. 
     
     
         32 . The method of  claim 21 , wherein the oxidative stress caused by ischemia-reperfusion injury. 
     
     
         33 . The method of  claim 21 , the oxidative stress caused by ataxia. 
     
     
         34 . The method of  claim 33 , wherein the ataxia includes Friedreich's ataxia.