Acid mucopolysaccharide metabolism in leprosy. 3. Hyaluronic acid mycobacterial growth enhancement, and growth suppression by saccharic acid and vitamin C as inhibitors of beta-glucuronidase.
A series of pilot studies are presented utilizing mouse and human infections with M. leprae and mouse infections with M. lepraemurium relating to the previously reported finding that hyaluronic acid seems to be a major nutrient substrate for these bacilli. The "feeding" of hyaluronic acid to the bacilli enhanced the growth of M. leprae in mouse abdominal walls and increased the Morphologic Index of M. lepraemurium infection. Saccharic acid, an inhibitor of beta-glucuronidase previously reported as present in these leprosy bacilli, caused marked regression of advanced M. lepraemurium infection, inhii. Ascorbic acid (vitamin C), also an inhibitor of beta-glucuronidase, given at a level of 1.5 gm/day for 4.5 months to one lepromatous patient without other treatment and for up to 24 months to four other lepromatous patients receiving DDS, was accompanied by lesion regression and changes in bacillary morphology similar to those seen in the inhibitor treated mice. If these observations are confirmed the possible use of beta-glucuronidase inhibitors as a useful adjunct to other leprosy therapy is raised as is also the likelihood of developing new therapies.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D003622:Dapsone / Q000627:therapeutic use; D003864:Depression, Chemical; D005260:Female; D005937:Glucaric Acid / Q000494:pharmacology / Q000627:therapeutic use*; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology*; D007918:Leprosy / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009164:Mycobacterium Infections / Q000188:drug therapy / Q000378:metabolism*; D009166:Mycobacterium leprae / Q000187:drug effects / Q000254:growth & development*; D009167:Mycobacterium lepraemurium / Q000187:drug effects / Q000254:growth & development*; D013268:Stimulation, Chemical; D013400:Sugar Acids / Q000627:therapeutic use*
D013400:Sugar Acids; D003622:Dapsone; D006820:Hyaluronic Acid; D005966:Glucuronidase; D001205:Ascorbic Acid; D005937:Glucaric Acid