Methods for treating injury associated with exposure to an alkylating species

Abstract

Compounds may be administered to prevent or rescue organ injury following exposure to alkylating agents, such as sulfur mustards. The compounds may be substituted metalloporphyrins.

1 . A method of treating an injury associated with exposure to an alkylating agent in a subject, wherein the alkylating agent is phosgene, said method comprising the step of:
 administering to a subject in need thereof an effective amount of a compound of formula   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the compound is bound to a metal. 
     
     
         3 . The method of  claim 2 , wherein the metal is selected from the group consisting of manganese, iron, cobalt, copper, nickel, and zinc. 
     
     
         4 . The method of  claim 3 , wherein the compound is bound to manganese. 
     
     
         5 .- 8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         10 .- 11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the injury is an injury to an organ in the subject. 
     
     
         13 . The method of  claim 12 , wherein the organ is skin, lungs, nose, esophagus, trachea, or bronchi. 
     
     
         14 .- 15 . (canceled) 
     
     
         16 . The method of  claim 1 , wherein said administration is selected from the group consisting of inhalation administration, topical administration, intravenous administration, subcutaneous administration, intraperitonal administration, and intramuscular administration. 
     
     
         17 . The method of  claim 1 , wherein exposure to the alkylating agent produces mitochondrial dysfunction. 
     
     
         18 . The method of  claim 17 , wherein the mitochondrial dysfunction causes an increase in reactive oxygen species production or oxidative stress. 
     
     
         19 . The method of  claim 1 , wherein the exposure to the alkylating agent relative to non-exposure to the alkylating agent, causes an increase in lactate dehydrogenase (LDH) levels, an increase in IgM levels, a decrease of glutathione levels, and an increase in myleperoxidase levels. 
     
     
         20 . The method of  claim 1 , wherein the compound is administered to the subject within about 0.5 hours to about 48 hours after exposure to the alkylating agent. 
     
     
         21 . The method of  claim 1 , wherein the compound is administered to the subject within about 1 hour to about 10 hours after exposure to the alkylating agent. 
     
     
         22 .- 32 . (canceled)