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Reduced cell death in skin flaps in rats treated with difluoromethylornithine
Author(s) -
Gelman Jack,
Bartolome Jorge V.,
Jenkins Scott,
Serafin Donald,
Schanberg Saul M.,
Klitzman Bruce
Publication year - 1987
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.1.6.3119414
Subject(s) - medicine , programmed cell death , chemistry , apoptosis , biochemistry
The beneficial effects of α‐difluoromethylornithine (DFMO) were assessed in a model of peripheral ischemia. DFMO is an irreversible inhibitor of ornithine decarboxylase (ODC), the initial enzyme in the production of polyamines. A 7 times 7 cm rat abdominal skin flap was surgically raised based on two inferior epigastric nerve, artery, and vein pedicles. One of the pedicles was then ligated and the skin was sutured back in place. Necrosis of skin was assessed 2 and 7 days after surgery. The rats were divided into four groups: control, DFMO, DFMO + polyamines, and polyamines alone. DFMO was administered in drinking water at 0.2%. Polyamines (putrescine, spermidine, and spermine) were each administered by daily i.p. injection at a dose of 10 mg/kg. The percentage of necrosis of the area of skin at risk in controls was 65 ± 2% (mean ± sem ). Necrosis was significantly reduced with DFMO (19 ± 1%), with DFMO plus polyamines (37 ± 3%), or with polyamines alone (41 ± 2%). Protein synthesis and ornithine decarboxylase activity in the skin were both significantly decreased by DFMO. These studies demonstrate that DFMO protects skin from ischemic damage at least in part through actions on polyamine metabolism.— G elman , J.; B artolome , J. V.; J enkins , S.; S erafin , D; S chanberg , S. M.; K litzman , B. Reduced cell death in skin flaps in rats treated with difluoromethylornithine. FASEB J. 1: 474‐477; 1987.