Nitric oxide donors retard wound healing in cultured rabbit gastric epithelial cell monolayers.
Effects of nitric oxide (NO) on gastric wound healing were investigated in primary rabbit gastric epithelial cell cultures. We analyzed the speed of cell migration, proliferation, and apoptosis after creating a round wound on the cell cultures. The monolayers were incubated with or without the NO donor sodium nitroprusside, oxatriazolimine 1,2,3,4-oxatriazolium, 5amino-3-(3,4-dichlorophenylchloride), or the peroxynitrite generator 3-morpholinosydnomine-N-ethylcarbamide. The possible role of cGMP as a second messenger of NO was investigated with 8-bromo-cGMP. The role of O2(-*) was evaluated using diethyldithiocarbamate and pyrogallol. The effects of superoxide dismutase and allopurinol were also investigated. NO inhibited the speed of cell migration and proliferation and induced cell apoptosis in a dose- and time-dependent manner. The effects were augmented with O2(-*) generators and ameliorated by O2-(8) scavengers, whereas cGMP had no significant effect on wound healing. NO donors retard gastric wound healing by inhibiting migration and proliferation and inducing cell apoptosis. These effects do not seem to be mediated via cGMP, but O2(-*). or peroxynitrites may be involved.
Kiviluoto
T
T
Department of Surgery, Helsinki University Central Hospital, 00029 Helsinki, Finland. tuula.kiviluoto@hus.fi
Watanabe
S
S
Hirose
M
M
Sato
N
N
Mustonen
H
H
Puolakkainen
P
P
Rönty
M
M
Ranta-Knuuttila
T
T
Kivilaakso
E
E
D000818:Animals; D002478:Cells, Cultured; D004050:Ditiocarb; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005753:Gastric Mucosa / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000494:pharmacology; D011748:Pyrogallol / Q000494:pharmacology; D011817:Rabbits; D014945:Wound Healing / Q000187:drug effects*
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D011748:Pyrogallol; D030421:Peroxynitrous Acid; D009599:Nitroprusside; D004050:Ditiocarb; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester