CYCLOSPORINE-A REDUCES THE SEVERITY OF COLD-RESTRAINT-INDUCED GASTRIC-LESIONS - ROLE OF LEUKOCYTES

The objective of this study was to determine the role of cyclosporin A (CsA) on cold-restraint-induced gastric lesions. Animals were subject ed to 3 h immobilization at 4 degrees C in plastic restraining devices following a starvation period of 48 h. Gastric samples were obtained for the measurement of myeloperoxidase (MPO) activity, an index of num ber of peroxidase positive cells and thiobarbituric acid-reactive subs tances (TBARS; lipid peroxidation). Animals were pretreated with CsA w hich is a potent immunosuppressant and inhibits ischemia/reperfusion-i nduced polymorphonuclear leukocyte (PMN) infiltration. Cold-restraint administration significantly elevated the tissue MPO activity and TEAR S formation. CsA pretreatment significantly reduced the severity of co ld-restraint-induced gastric lesions while attenuating the elevated MP O measurements observed during cold-restraint administration. Animals rendered neutropenic with antineutrophil serum (ANS) exhibited signifi cantly less gastric mucosal injury normally observed after cold-restra int stress. Neither CsA nor ANS treatment effected the elevated TEAR l evels, indicating that PMNs are not involved in the lipid peroxidation process observed after cold-restraint stress. In conclusion, the resu lts of this study indicate that CsA is capable of inhibiting cold-rest raint-induced gastric mucosal injury and can attenuate the cold-restra int-induced increases in gastric MPO measurements. Our results also in dicate that PMNs may be the important mediators of cold-restraint-indu ced gastric lesions.