Cigarette smoke extracts delay wound healing in the stomach: involvement of polyamine synthesis

The association between cigarette smoking and peptic ulcer diseases has been well established. Ornithine decarboxylase (ODC) is crucial for the gastroprotective and mucosal growth promoting effects in gastric ulcer healing. The aim of this study is to elucidate the possible mechanism of how inhibition of ODC activity is involved in the delay of ulcer healing, if any, by cigarette smoke extracts (CSE). CSE were fractionated into chloroform extract (CE) and ethanol extract (EE). In in vivo study, rats with acetic acid-induced ulcers were given CE or EE intragastrically (2.5 or 5 mg/kg) once daily for 3 days. Ulcer sizes were significantly larger after CE or EE administration, followed by an increase in myeloperoxidase activity and a reduction in cell proliferation. However, both CSE stimulated the number of microvessels following the increase of basic fibroblast growth factor. In in vitro studies, the effect of CE or EE (10, 40, or 100 microg/ml) on cell migration and cell proliferation were measured using an in vitro wound model and [(3)H]-thymidine incorporation assay, respectively. Both CSE delayed cell migration and decreased cell proliferation, which were accompanied with a reduction in ODC activity. Exogenous spermidine (5 or 10 microM) could reverse the inhibitory action on cell proliferation and ODC activity induced by CSE. In conclusion, both CSE significantly delayed ulcer healing as a result of reduction in cell proliferation and cell migration. All these effects are, in part, related to the reduction of polyamine synthesis.