Cyclosporin 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 subjected 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 number of peroxidase positive cells and thiobarbituric acid-reactive substances (TBARS; lipid peroxidation). Animals were pretreated with CsA which is a potent immunosuppressant and inhibits ischemia/reperfusion-induced polymorphonuclear leukocyte (PMN) infiltration. Cold-restraint administration significantly elevated the tissue MPO activity and TBARS formation. CsA pretreatment significantly reduced the severity of cold-restraint-induced gastric lesions while attenuating the elevated MPO measurements observed during cold-restraint administration. Animals rendered neutropenic with antineutrophil serum (ANS) exhibited significantly less gastric mucosal injury normally observed after cold-restraint stress. Neither CsA nor ANS treatment effected the elevated TBAR levels, indicating that PMNs are not involved in the lipid peroxidation process observed after cold-restraint stress. In conclusion, the results of this study indicate that CsA is capable of inhibiting cold-restraint-induced gastric mucosal injury and can attenuate the cold-restraint-induced increases in gastric MPO measurements. Our results also indicate that PMNs may be the important mediators of cold-restraint-induced gastric lesions.
Coşkun
T
T
Department of Physiology, Marmara University School of Medicine, Istanbul, Turkey.
Alican
I
I
Yeğen
B C
BC
San
T
T
Cetinel
S
S
Kurtel
H
H
D000818:Animals; D003080:Cold Temperature / Q000009:adverse effects; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D007106:Immune Sera / Q000494:pharmacology; D008297:Male; D008855:Microscopy, Electron, Scanning; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000009:adverse effects; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control*; D013312:Stress, Physiological / Q000150:complications*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D007106:Immune Sera; D017392:Thiobarbituric Acid Reactive Substances; D016572:Cyclosporine; D009195:Peroxidase