Treatment of oxidative stress disorders including contrast nephropathy, radiation damage and disruptions in the function of red cells

Abstract

Methods of treating or suppressing oxidative stress diseases and symptoms related to oxidative stress affecting normal electron flow in the cells or caused by reactive oxygen species with redox-active therapeutics. Use of redox-active therapeutics for the reduction, suppression or treatment of oxidative stress induced by chemical agents such as contrast agents and other nephrotoxic agents, by radiation exposure, and by disruptions in the transport of oxygen to tissues, is disclosed.

1 . A method for treating an oxidative stress disorder in a mammal 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:
 compounds of Formula II:   
       
         
           
           
               
               
           
         
         and the hydroquinone forms thereof; 
         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 
         wherein the oxidative stress disorder is a hemoglobinopathy. 
       
     
     
         2 - 19 . (canceled) 
     
     
         20 . The method according to  claim 1 , wherein the redox-active therapeutic is a compound of Formula II 
       or a stereoisomer, or a mixture of stereoisomers thereof. 
     
     
         21 - 24 . (canceled) 
     
     
         25 . The method according to  claim 1 , wherein the redox-active therapeutic is the hydroquinone form of a compound of Formula II or a stereoisomer, or a mixture of stereoisomers thereof. 
     
     
         26 . The method according to  claim 1 , wherein R 21 , R 22 , and R 23  are independently selected from the group consisting of (C 1 -C 4 )-alkyl. 
     
     
         27 . The method according to  claim 1 , wherein R 24  is selected from the group consisting of (C 1 -C 20 )-alkyl. 
     
     
         28 . The method according to  claim 20 , wherein R 21 , R 22 , and R 23  are independently selected from the group consisting of (C 1 -C 4 )-alkyl. 
     
     
         29 . The method according to  claim 20 , wherein R 24  is selected from the group consisting of (C 1 -C 20 )-alkyl. 
     
     
         30 . The method according to  claim 1 , wherein the redox-active therapeutic is selected from the group consisting of: 2-octyl-3,5,6-trimethyl-[1,4]benzoquinone, 2-hexyl-3,5,6-trimethyl-[1,4]benzoquinone, and the hydroquinone forms thereof. 
     
     
         31 . The method according to  claim 1 , wherein the hemoglobinopathy is sickle-cell disease. 
     
     
         32 . The method according to  claim 29 , wherein the hemoglobinopathy is sickle-cell disease. 
     
     
         33 . The method according to  claim 30 , wherein the hemoglobinopathy is sickle-cell disease. 
     
     
         34 . The method according to  claim 1 , wherein the hemoglobinopathy is a thalassemia. 
     
     
         35 . The method according to  claim 34 , wherein the thalassemia is alpha-thalassemia. 
     
     
         36 . The method according to  claim 34 , wherein the thalassemia is beta-thalassemia. 
     
     
         37 . The method according to  claim 34 , wherein the thalassemia is beta-thalassemia major. 
     
     
         38 . The method according to  claim 1 , wherein the redox-active therapeutic is administered in a pharmaceutical composition comprising the redox-active therapeutic and a pharmaceutically acceptable excipient, pharmaceutically acceptable carrier, or pharmaceutically acceptable vehicle.