Treatment and prevention of reactive oxygen metabolite-mediated cellular damage

Abstract

The present invention relates to a method for preventing and/or reducing cellular and tissue damage caused by reactive oxygen metabolites (ROMs) released by phagocytic or endothelial cells in response to various disease states or pathologies. The methods of the present invention are useful in preventing and treating a variety of disease states or pathological situations in which ROMs are produced and released. The methods of the present invention contemplate reducing ROM-mediated damage by reducing the production and release of ROMs.

What is claimed is:  
     
         1 . A kit for the treatment of a condition caused or exacerbated by ROM-mediated damage, comprising: 
 an infusion device; and    a compound effective to inhibit the production or release of the ROMs, wherein the ROM production or release compound is selected from the group consisting of histamine, histamine phosphate, histamine dihydrochloride, and H 2  receptor agonists.    
     
     
         2 . The kit of  claim 1 , wherein the infusion device is adapted to administer the compound by a method selected from the group consisting of injection, implantation infusion device, inhalation, ingestion, diffusion and by suppository.  
     
     
         3 . The kit of  claim 1 , wherein the infusion device is selected from the group consisting of pre-loaded syringes, syringe pumps, auto injector systems and minipumps.  
     
     
         4 . The kit of  claim 2 , wherein the injection method is selected from the group consisting of subcutaneous injection, intramuscular injection and intravenous injection.  
     
     
         5 . The kit of  claim 2 , wherein the diffusion method is selected from the group consisting of transdermal diffusion and transmucosal diffusion.  
     
     
         6 . The kit of  claim 1 , further comprising an effective amount of a ROM scavenger.  
     
     
         7 . The kit of  claim 6 , wherein the ROM scavenger is selected from the group consisting of catalase, glutathione peroxidase, ascorbate peroxidase, superoxide dismutase, glutathione peroxidase, ascorbate peroxidase, vitamin A, vitamin E, and vitamin C.  
     
     
         8 . The kit of  claim 6 , wherein the infusion device is adapted to administer the compound by a method selected from the group consisting of injection, implantation infusion device, inhalation, ingestion, diffusion and by suppository.  
     
     
         9 . The kit of  claim 1 , further comprising an analgesic, an anesthetic or an anxiolytic compound.  
     
     
         10 . The kit of  claim 1 , further comprising IL-3, a retinoid, an allergen, a 5HT agonist, serotonin, and diphenyleneiodonium.  
     
     
         11 . The kit of  claim 1 , wherein said condition is radiation injury.  
     
     
         12 . A pre-loaded delivery device, comprising a compound effective to inhibit the production or release of the ROMs, wherein the ROM production or release compound is selected from the group consisting of histamine, histamine phosphate, histamine dihydrochloride, and H 2  receptor agonists, and a compound effective for the scavenging of ROMs.  
     
     
         13 . The pre-loaded delivery device of  claim 12 , wherein said delivery device is a syringe.  
     
     
         14 . The pre-loaded delivery device of  claim 12 , wherein said compound effective for the scavenging of ROMs is selected from the group consisting of catalase, glutathione peroxidase, ascorbate peroxidase, superoxide dismutase, glutathione peroxidase, ascorbate peroxidase, vitamin A, vitamin E, and vitamin C.  
     
     
         15 . The pre-loaded delivery device of  claim 12 , wherein said device comprises 0.4 mg to 10 mg of histamine.  
     
     
         16 . The pre-loaded delivery device of  claim 12 , wherein said device comprises 0.1 to 10 mg of an enzymatic ROM scavenger.  
     
     
         17 . The pre-loaded delivery device of  claim 12 , wherein said device comprises 1.0 picogram to 1 mg of a mineral non-enzymatic ROM scavenger.  
     
     
         18 . The pre-loaded delivery device of  claim 12 , wherein said composition comprises 1 to 5000 IU of a non-enzymatic ROM scavenger selected from the group consisting of vitamin A and vitamin E.  
     
     
         19 . A method for treating a subject suffering from radiation injury, comprising: 
 identifying a subject presenting the symptoms of radiation injury caused or exacerbated by release of reactive oxygen metabolites (“ROMs”) from phagocytic cells resulting in ROM-mediated oxidative damage; and    administering a compound effective to inhibit the production or release of the ROMs and a compound effective for the scavenging of ROMs with the pre-loaded delivery device of  claim 12.