Altering expression level of glutathione S-transferase genes by treating a human subject with a nitroxide
View Patent ↗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 the GST gene is upregulated,
the oxidative stress caused by a disease or condition selected from the group consisting of cancer, rheumatoid/osteoid arthritis, systemic lupus erythematosus (SLE), inflammatory bowel disease, Alzheimer's disease, multiple sclerosis, atherosclerosis, cardiovascular disease, cataracts, dementia, osteoporosis, type 2 diabetes, chemotherapy, radiation therapy and hypertension, and
the nitroxide antioxidant 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.
2. The method of claim 1 , wherein the GST gene is selected from the group consisting of Gstm3, Gstm6, Gsta3, Gstt1, Gsta4, Gstm1, Gstm4, Gstt2, Gstp1, and Gstk1.
3. The method of claim 2 , wherein the nitroxide antioxidant is 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL).
4. The method of claim 1 , wherein the individual has been administered a chemotherapeutic agent.
5. The method of claim 1 , wherein the nitroxide antioxidant is chemically attached to one or more bioeffector molecules.
6. The method of claim 1 , further comprising administering to the individual a xenobiotic prior to administering to the individual the effective amount of the nitroxide antioxidant.
7. The method of claim 1 , wherein the effective amount of the nitroxide antioxidant comprises about 5 mg/g of food.
8. The method of claim 1 , wherein the effective amount of the nitroxide antioxidant comprises about 500-1500 mg/g.
9. The method of claim 3 , wherein the oxidative stress caused by cancer.
10. The method of claim 3 , wherein the oxidative stress caused by rheumatoid/osteoid arthritis.
11. The method of claim 3 , wherein the oxidative stress caused by systemic lupus erythematosus (SLE).
12. The method of claim 3 , wherein the oxidative stress caused by inflammatory bowel disease.
13. The method of claim 3 , wherein the oxidative stress caused by Alzheimer's disease.
14. The method of claim 3 , wherein the oxidative stress caused by multiple sclerosis.
15. The method of claim 3 , wherein the oxidative stress caused by atherosclerosis.
16. The method of claim 3 , wherein the oxidative stress caused by cardiovascular disease.
17. The method of claim 3 , wherein the oxidative stress caused by cataracts.
18. The method of claim 3 , wherein the oxidative stress caused by dementia.
19. The method of claim 3 , wherein the oxidative stress caused by osteoporosis.
20. The method of claim 3 , wherein the oxidative stress caused by type 2 diabetes.
21. The method of claim 3 , wherein the oxidative stress caused by chemotherapy.
22. The method of claim 3 , wherein the oxidative stress caused by radiation therapy.
23. The method of claim 3 , wherein the oxidative stress caused by hypertension.