TREATMENT OF OXIDATIVE STRESS DISORDERS INCLUDING CONTRAST NEPHROPATHY, RADIATION DAMAGE AND DISRUPTIONS IN THE FUNCTION OF RED CELLS

1 . A method for reducing, preventing or treating an oxidative stress disorder in a mammal having or prone to having an oxidative stress disorder said method comprising administering to the mammal a therapeutically effective amount of a redox-active therapeutic, wherein the redox-active therapeutic is selected from the group consisting of:

(a) compounds of Formula I:

wherein,

the bonds indicated with a dashed line are all single or all double, R 1 , R 2 , and R 3 are independently selected from the group consisting of H, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-haloalkyl, CN, F, Cl, Br, and I; and

R 4 and R 5 are independently selected from the group consisting of hydroxy and (C 1 -C 4 )-alkyl, and R 6 is hydrogen; or

R 4 is (C 1 -C 4 )-alkyl, and R 5 and R 6 are hydrogen; or

R 4 is (C 1 -C 4 )-alkyl, and R 5 and R 6 together form a double bond;

or a stereoisomer, or a mixture of stereoisomers thereof;

(b) compounds of Formula II:

wherein,

R 21 , R 22 , and R 23 are independently selected from the group consisting of H, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-haloalkyl, CN, F, Cl, Br, and I:,

R 24 is independently selected from the group consisting of (C 1 -C 20 )-alkyl, (C 2 -C 20 )-alkenyl, (C 2 -C 20 )-alkynyl, and (C 4 -C 20 ) containing at least one double bond and at least one triple bond;

or a stereoisomer, or a mixture of stereoisomers thereof; and

(c) compounds of Formula V:

wherein,

R 51 , R 52 , and R 53 are independently selected from the group consisting of hydrogen and (C 1 -C 6 )-alkyl;

R 54 is (C 1 -C 6 )-alkyl;

R 55 and R 56 are independently selected from the group consisting of hydrogen, hydroxy, alkoxy, (C 1 -C 40 )-alkyl, (C 2 -C 40 )-alkenyl, (C 2 -C 40 )-alkenyl, and aryl; where the alkyl, alkenyl, alkenyl and aryl groups are optionally substituted with

—OR 501 , —S(O) 0-2 R 501 , —CN, —F, —Cl, —Br, —I, —NR 501 R 502 , oxo, (C 3 -C 6 )-cycloalkyl, aryl, aryl (C 1 -C6)-alkyl, heteroaryl, heterocyclyl, —C(═O)—R 503 , —C(═O)—(C 0 -C 6 )-alkyl-aryl, —C(═O)—O-R 503 , —C(═O)—O—(C 0 -C 6 )-alkyl-aryl, —C(═O)—N—R 503 R 504 , —C(═O)—NH—(C 0 -C 6 )-alkyl-aryl, —NH—C(═O)—R 503 , —NH—C(═O)—(C 0 -C 6 )-alkyl-aryl; where the aryl, heteroaryl and heterocyclyl ring substituents may be further substituted with (C 1 -C 6 )-alkyl, (C 1 -C 6 )-haloalkyl, oxo, hydroxy, (C 1 -C 6 )-alkoxy, —C(═O)—(C 1 -C 6 )-alkyl, or —C(═O)—O—(C 1 -C 6 )-alkyl; and where one of the carbons of the alkyl, alkenyl, or alkynyl groups is optionally replaced with a heteroatom selected from the group consisting of 0, N and S; or

R 55 and R 56 together with the nitrogen atom to which they are attached form a saturated or unsaturated 3-8 membered ring, optionally incorporating one or more additional heteroatoms which are independently N, O, or S, and optionally substituted with oxo, —OR 501 , —SR 501 , —CN, —F, —Cl, —Br, —NR 501 R 502 , (C 1 -C 6 )-alkyl, (C 1 -C 6 )-haloalkyl, hydroxy-(C 1 -C 6 )-alkyl-, —C(═O)—H, —C(═O)—(C 1 -C 6 )-alkyl, —C(═O)-aryl, —C(═O)—OH, or —C(═O)—O—(C 1 -C 6 )-alkyl;

or a pharmaceutically acceptable salt, a stereoisomer, or a mixture of stereoisomers thereof; and

wherein the oxidative stress disorder induces renal damage in the mammal due to the administration, ingestion, absorption of, or exposure to a nephrotoxic agent or wherein the oxidative stress is induced by exposure to radiation; or wherein the oxidative stress disorder is selected from the group consisting of hemoglobinopathy, sickle cell anemia, and thalassemia.

2 - 6 . (canceled)

7 . The method according to claim 1 , wherein the oxidative stress disorder induces renal damage in the mammal due to the administration, ingestion, absorption of, or exposure to a nephrotoxic agent.

8 . The method according to claim 7 , wherein the nephrotoxic agent is a contrast agent.

9 . The method according to claim 8 , wherein the nephrotoxic agent is an iodinated, brominated, barium-containing, or gadolinium-containing contrast agent.

10 . The method according to claim 8 , where the nephrotoxic agent is selected from the group of a non-steroidal anti-inflammatory drug, cisplatin, methotrexate, acyclovir, gentamicin, and an ACE inhibitor.

11 . The method according to claim 1 , where the oxidative stress is induced by exposure to radiation.

12 . The method according to claim 11 , where the radiation is selected from the group consisting of diagnostic X-rays, radiation therapy in cancer treatment, CAT-scans, mammograms, radionuclide scans, interventional radiological procedures under computed tomography or fluoroscopy guidance, tissue-incorporated radionuclides from ingestion of contaminated food or water, and uncontrolled exposure to ionizing radiation from nuclear weapons, radioactive spills, or cosmic radiation.

13 . The method according to claim 1 , for preventing death of radiation-injured or radiation-damaged non-cancerous cells, comprising administering to a mammal in need thereof, prior to an exposure to radiation, a therapeutically effective amount of the redox-active therapeutic.

14 . The method according to claim 1 , for reducing an effect of radiation on normal cells in a mammal at risk for incurring exposure to radiation, comprising administering to the mammal prior to an exposure to radiation, a therapeutically effective amount of the redox-active therapeutic.

15 . The method according to claim 1 , for reducing an effect of radiation on normal cells in a mammal exposed to ionizing radiation, comprising administering to the mammal subsequent to an accidental or intentional release of radioactive materials, a therapeutically effective amount of [[a]] the redox-active therapeutic.

16 . The method according to claim 1 , for protecting non-cancerous cells against radiation therapy, comprising administering to the mammal prior to an exposure to radiation therapy, a therapeutically effective amount of the redox-active therapeutic.

17 . The method according to claim 1 , where the method is an improved radiotherapy for treatment of cancer, comprising administering the mammal a therapeutically effective amount of the redox-active therapeutic, and then administering to the mammal an effective amount of radiation, such that radiation injury to normal cells is decreased or eliminated.

18 . The method according to claim 1 , wherein the redox-active therapeutic comprises a compound of Formula I

or a stereoisomer, or a mixture of stereoisomers thereof.

19 . The method according to claim 18 , wherein the redox-active therapeutic comprises the compound of Formula I wherein,

the bonds indicated with a dashed line are all single or all double;

R 1 , R 2 , and R 3 are independently selected from (C 1 -C 4 )-alkyl;

R 4 is hydroxy;

R 5 is (C 1 -C4)-alkyl, and

R 6 is hydrogen;

or a stereoisomer, or a mixture of stereoisomers thereof

20 . The method according to claim 1 , wherein the redox-active therapeutic comprises a compound of Formula II

or a stereoisomer, or a mixture of stereoisomers thereof.

21 - 22 . (canceled)

23 . The method according to claim 1 , wherein the redox-active therapeutic comprises a compound of Formula V;

or a pharmaceutically acceptable salt, a stereoisomer, or a mixture of stereoisomers thereof.

24 . (canceled)

25 . The method according to claim 1 , wherein the redox-active therapeutic is alpha-tocopherol quinone.

26 . The method according to claim 1 , wherein the redox-active therapeutic is alpha-tocotrienol quinone.

27 . The method according to claim 1 , wherein the redox-active therapeutic is 2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide.