# US 10,441,578 B2 · Altering expression level of glutathione S-transferase genes by treating a human subject with a nitroxide

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- Number: US 10,441,578 B2
- Document ID: US10441578B2
- Status: Granted
- Kind: B2
- Application number: 15/875,872
- Filed: 2018-01-19
- Published: 2019-07-25
- Granted: 2019-10-15
- Earliest claimed: 2018-01-19
- Applicants: Louis Habash
- Inventors: Louis Habash
- Web page: https://patentgrep.com/patent/US10441578B2

## CPC

- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 2)

The method of claim 2, wherein the nitroxide antioxidant is 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL).

### Claim 4 (depends on 1)

The method of claim 1, wherein the individual has been administered a chemotherapeutic agent.

### Claim 5 (depends on 1)

The method of claim 1, wherein the nitroxide antioxidant is chemically attached to one or more bioeffector molecules.

### Claim 6 (depends on 1)

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.

### Claim 7 (depends on 1)

The method of claim 1, wherein the effective amount of the nitroxide antioxidant comprises about 5 mg/g of food.

### Claim 8 (depends on 1)

The method of claim 1, wherein the effective amount of the nitroxide antioxidant comprises about 500-1500 mg/g.

### Claim 9 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by cancer.

### Claim 10 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by rheumatoid/osteoid arthritis.

### Claim 11 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by systemic lupus erythematosus (SLE).

### Claim 12 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by inflammatory bowel disease.

### Claim 13 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by Alzheimer's disease.

### Claim 14 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by multiple sclerosis.

### Claim 15 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by atherosclerosis.

### Claim 16 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by cardiovascular disease.

### Claim 17 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by cataracts.

### Claim 18 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by dementia.

### Claim 19 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by osteoporosis.

### Claim 20 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by type 2 diabetes.

### Claim 21 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by chemotherapy.

### Claim 22 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by radiation therapy.

### Claim 23 (depends on 3)

The method of claim 3, wherein the oxidative stress caused by hypertension.
