ROLE OF INTRACELLULAR 2ND MESSENGERS AND REACTIVE OXYGEN SPECIES IN THE PATHOPHYSIOLOGY OF V-CHOLERA O139 TREATED RABBIT ILEUM

Vibrio cholerae O139 has pandemic potential and it produces copious am ounts of fluid secretion. The levels of various second messengers (int racellular Ca2+, cAMP, IP3, PKC) were measured to determine the cause of fluid secretion produced by this strain of V. cholerae. There was a significant increase in the levels of these second messengers in V. c holer ae O139 treated ileum as compared to control ileum (enterocytes) . Levels of these second messengers were also assessed in V. cholerae 569B induced fluid secretion in rabbit ileum and it was found that the levels were raised more in V. cholerae O139 treated ileum than in V. cholerae 569B treated rabbit ileum. The intestinal damage was assessed by measuring changes in the extent of lipid peroxidation of the enter ocytes. Intracellular second messengers are known to raise the extent of lipid peroxidation. In V. cholerae O139 treated loops calcium ionop hore A23187 enhanced the extent of lipid peroxidation whereas L-verapa mil could only marginally decrease the lipid peroxidation. Dantrolene and H-7 significantly decreased the extent of lipid peroxidation of en terocytes in V. cholerae O139 treated rabbit ileum. However: PMA could not enhance further the extent of lipid peroxidation in V. cholerae O 139 treated rabbit ileum. So intracellular calcium and protein kinase C appear to be involved in intestinal damage caused by V. cholerae O13 9. Reactive oxygen species are responsible for causing tissue damage a nd the extent of oxidative damage depends on the balance between the p ro-oxidants and the anti-oxidants. So the changes in the enterocytes' antioxidant level during V. cholerae O139 mediated intestinal infectio n was estimated. There was a significant decrease in the enterocyte le vel of the antioxidant enzymes SOD, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase and glucose-6-phosphate dehydrogenase in V. cholerae O139 mediated intestinal infection. So a significant decrease in the levels of antioxidant defenses and a sign ificant increase in the levels of second messengers appear to be impor tant in mediating V. cholerae O139 induced lipid peroxidation which co ntributes to the changes in membrane permeability and thus to fluid se cretion. (C) 1998 Elsevier Science B.V. All rights reserved.