Compositions for anti-inflammatory, antioxidant effects and improved respiratory function by specific histone deacetylase inhibition

Abstract

Compositions comprising LSF compositions and treatment regiments comprising administration of LSF containing compositions are disclosed. Compositions and/or regiments may optionally include the administration of vitamins, minerals, and anti-oxidants. Methods for using these compositions and treatment regimens for treating subjects for diseases, including diseases associated with inflammation and/or oxidative stress, are provided. Various methods for use of the LSF compositions for inhibition of histone deacetylases (HDACs) in various cells, tissues, and/or conditions are also provided.

1 - 20 . (canceled) 
     
     
         21 . A method for protecting cardiac myocytes in a cell, tissue or animal, comprising selecting a cell, tissue or animal comprising cardiac myocytes that has been contacted with doxorubicin and contacting said cell, tissue or animal with a composition comprising L-sulforaphane (LSF), an LSF derived and/or substituted compound, and/or an LSF analogue, wherein the LSF, LSF derived and/or substituted compound, and/or an LSF analogue has the following formula: 
       
         
           
           
               
               
           
         
       
       wherein R is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted acyl, ORa, SRa, SORa, SO2Ra, OSO2Ra, OSO3Ra, NO2, NHRa, N(Ra)2, ═N—Ra, N(Ra)CORa, N(CORa)2, N(Ra)SO2R′, N(Ra)C(═NRa)N(Ra)Ra, CN, halogen, CORa, COORa, OCORa, OCOORa, OCONHRa, OCON(Ra)2, CONHRa, CON(Ra)2, CON(Ra)ORa, CON(Ra)SO2Ra, PO(ORa)2, PO(ORa)Ra, PO(ORa)(N(Ra)Ra) and amino acid ester having inhibitory efficacy against the LSD1 protein; and further wherein each of the Ra groups is independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl, substituted or unsubstituted acyl; and further wherein each of the substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and/or acyl groups are C1-28 (including all ranges therein), and protecting said cardiac myocytes in said cell, tissue or animal by reducing doxorubicin-induced DNA damage compared to a cell, tissue or animal contacted with doxorubicin and not contacted with said composition. 
     
     
         22 . The method of  claim 21 , further comprising contacting said cell, tissue or animal with one or more of hydroxytyrosol, oleuropein, N-acetylcysteine, L-proline, glycine, and taurine. 
     
     
         23 . The method of  claim 21 , wherein γH2AX in said cell, tissue or animal is decreased after contact with said composition. 
     
     
         24 . The method of  claim 21 , wherein said reduction in doxorubicin-induced DNA damage improves viability of said cell, tissue or animal. 
     
     
         25 . The method of  claim 21 , wherein said LSF, LSF derived and/or substituted compound, and/or an LSF analogue has the following formula: 
       
         
           
           
               
               
           
         
       
     
     
         26 . The method of  claim 21 , wherein said composition comprises an amount of said LSF, LSF derived and/or substituted compound, and/or an LSF analogue that said composition if delivered to an animal comprises about 0.01 micrograms per kilogram of body weight to about 1000 micrograms per kilogram of body weight of said LSF, LSF derived and/or substituted compound, and/or an LSF analogue. 
     
     
         27 . The method of  claim 21 , wherein said composition comprises an amount of said LSF, LSF derived and/or substituted compound, and/or an LSF analogue that said composition if delivered to an animal comprises about 0.01 micrograms per kilogram of body weight to about 100 milligrams per kilogram of body weight of said LSF, LSF derived and/or substituted compound, and/or an LSF analogue. 
     
     
         28 . The method of  claim 21 , wherein said composition comprises an amount of said LSF, LSF derived and/or substituted compound, and/or an LSF analogue that said composition if delivered to an animal comprises about 5 to about 50 micrograms per kilogram of body weight of said LSF, LSF derived and/or substituted compound, and/or an LSF analogue. 
     
     
         29 . The method of  claim 21 , wherein about 0.01 to 100 milligrams of said LSF, LSF derived and/or substituted compound, and/or an LSF analogue is administered to said animal. 
     
     
         30 . The method of  claim 21 , wherein at least about 1 μM to about 100 μM LSF, LSF derived and/or substituted compound, and/or an LSF analogue is administered to said animal.