Method to enhance delivery of glutathione and ATP levels in cells

Abstract

A therapeutic method is provided comprising treating a mammal subject to hypoxia with an amount of 2(R,S)-D-ribo-(1′,2′,3′,4′-tetrahydroxybutyl)thiazolidine-4(R)-carboxylic acid (RibCys) or a pharmaceutically acceptable salt thereof effective to both maintain, restore or increase both the ATP levels and the glutathione (GSH) levels in said tissue.

1 . A therapeutic method comprising treating a mammal subject to hypoxia with an amount of 2(R,S)-D-ribo-(1′, 2′, 3′, 4′-tetrahydroxybutyl)thiazolidine-4(R)- carboxylic acid (RibCys) or a pharmaceutically acceptable salt thereof effective to both maintain, restore or increase both the ATP levels and the glutathione (GSH) levels in said tissue.  
   
   
       2 . The method of  claim 1  wherein the mammal is a human.  
   
   
       3 . The method of claims  1  or  2  wherein the RibCys is administered orally.  
   
   
       4 . The method of claims  1  or  2  wherein the RibCys is administered parenterally.  
   
   
       5 . The method of  claim 4  wherein the RibCys is administered intravenously or intraperitoneally.  
   
   
       6 . The method of claims  1  or  2  wherein the mammal was, is or will be subjected to ischemia insult.  
   
   
       7 . The method of  claim 6  wherein the tissue is cardiovascular tissue.  
   
   
       8 . The method of  claim 7  wherein the tissue is myocardial tissue.  
   
   
       9 . The method of  claim 6  wherein said ischemic insult is produced during heart surgery, organ transplantation, angioplasty or stenting.  
   
   
       10 . The method of  claim 9  wherein the RibCys solution is infused directly into a chamber of the heart or is infused intravenously.  
   
   
       11 . The method of  claim 6  wherein the ischemia is due to cardiovascular disease, cardiomyopathy, myocardial stunning, peripheral vascular disease, intermittent claudication, tachycardia or ischemia-reperfusion.  
   
   
       12 . The method of claims  1  or  2  wherein the hypoxia is due to an aesthesia, physical body weight pressure, septicemia, stroke, a surgical procedure, burn, pulmonary dysfunction, physical exertion or chronic illness.  
   
   
       13 . The method of  claim 12  wherein the body weight pressure causes pressure ulcers.  
   
   
       14 . The method of  claim 13  wherein the chronic illness is due to viral infection.  
   
   
       15 . The method of  claim 14  wherein the viral infection is due to HCMV, HIV or EBV.  
   
   
       16 . The method of  claim 13  wherein the chronic illness is due to bacterial infection.  
   
   
       17 . The method of  claim 13  wherein the chronic illness is cancer.  
   
   
       18 . A therapeutic method comprising administering RibCys to a mammal in an effective amount to increase the tolerance of the mammal to hypoxia so that ribose and cysteine are elevated in the tissue of the mammal during the hypoxic event.  
   
   
       19 . The method of  claim 18  wherein the mammal is a human.  
   
   
       20 . The method of claims  1 ,  2 ,  18  or  19  wherein RibCys is administered in a dosage of about 10 to 150 grams.  
   
   
       21 . The method of  claim 18  wherein the RibCys is administered at least five minutes prior to the occurrence of the hypoxic event.  
   
   
       22 . The method of claims  1 ,  2 ,  18  or  19  wherein the RibCys is administered in a liquid vehicle comprising an amount of free ribose effective to inhibit in vitro dissociation of RibCys prior to administration.