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. 2000 Aug;47(2):170–177. doi: 10.1136/gut.47.2.170

The role of polyamines in gastric mucus synthesis inhibited by cigarette smoke or its extract

L Ma 1, W Wang 1, J Chow 1, S Lam 1, C Cho 1
PMCID: PMC1728002  PMID: 10896906

Abstract

BACKGROUND—Cigarette smoking was shown to delay gastric ulcer healing and reduce synthesis of mucus, which is important for gastric ulcer protection and healing. Polyamines are important in these processes.
AIMS—To study the effects of cigarette smoking on the synthesis of mucus and to investigate if such an effect is acting by interference with the polyamine pathway.
METHODS—Gastric mucosal ornithine decarboxylase activity, mucous secreting layer thickness, and ulcer size were determined after different concentrations of cigarette smoke exposure (0, 2, or 4%) in intact animals and animals with ulcers. Synthesis of mucus and ornithine decarboxylase activity and mRNA expression were also assessed in cigarette smoke extract treated MKN-28 cells.
RESULTS—Exposure to cigarette smoke significantly reduced the thickness of the mucous secreting layer and gastric mucosal ornithine decarboxylase activity in animals with or without ulcers. Spermidine not only reversed inhibition of mucus synthesis in both intact and ulcer bearing animals but also reversed the delay in ulcer healing. Cigarette smoke extract significantly reduced mucus synthesis and ornithine decarboxylase activity but not its mRNA expression in MKN-28 cells. The reduction in mucus synthesis was restored by spermidine. 
CONCLUSIONS—Cigarette smoke and its extract repress mucus synthesis in vivo and in vitro, respectively. Reduction of ornithine decarboxylase activity in gastric mucosa is closely associated with this effect.


Keywords: mucus; ornithine decarboxylase; cigarette smoking; ulcers

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Figure 1  .

Figure 1  

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Effect of exposure to cigarette smoke on the mucous secreting layer in intact rats. Rats were exposed to cigarette smoke (0, 2, or 4%) for one hour each day for three, six, or nine days. Values are mean (SEM) of 7-8 rats. **p<0.01, ***p<0.001 v 0% exposure.

Figure 2  .

Figure 2  

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Effect of exposure to cigarette smoke on gastric mucosal ornithine decarboxylase (ODC) activity in (A) intact and (B) ulcerated rats. ODC activity was determined by the amount of 14CO2 liberated. Both intact and ulcerated rats (24 hours after ulcer induction) were exposed to cigarette smoke (0, 2, or 4%) for one hour each day for three or six days. ODC activity was measured in the gastric mucosa. Values are mean (SEM) of 7-8 rats. *p<0.05, **p<0.01 v 0% exposure.

Figure 3  .

Figure 3  

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Effect of exposure to cigarette smoke on the mucous secreting layer in rats, four (A) and seven (B) days after ulcer induction. Twenty four hours after ulcer induction, rats were exposed to cigarette smoke (0, 2, or 4%) for one hour each day for three or six days. Values are mean (SEM) of 10-12 rats. *p<0.05, **p<0.01, ***p<0.001 v 0% exposure.

Figure 4  .

Figure 4  

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Effects of cigarette smoke extract and DL-α-difluoromethyl-ornithine (DFMO) on mucus synthesis in MKN-28 cells. Cells were incubated with cigarette smoke extract, DFMO, or vehicle for six hours. Mucus synthesis was determined by the amount of [3H] glucosamine incorporation. Values are mean (SEM) of six samples. ***p<0.001 v vehicle.

Figure 5  .

Figure 5  

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Effect of cigarette smoke extract on ornithine decarboxylase (ODC) activity in MKN-28 cells. Cells were incubated with cigarette smoke extract or vehicle for six hours. ODC activity was determined by the amount of 14CO2 liberated. Values are mean (SEM) of six samples. **p<0.01, ***p<0.001 v vehicle.

Figure 6  .

Figure 6  

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Effects of polyamines on mucus synthesis in MKN-28 cells in the absence (A) and presence (B) of cigarette smoke extract. Cells were incubated with vehicle, polyamines, cigarette smoke extract, or a combination of spermidine and smoke extract for six hours. Mucus synthesis was determined by the amount of [3H] glucosamine incorporation. Values are mean (SEM) of six samples. **p<0.01, **p<0.001 v vehicle; †††p <0.001 v cigarette smoke extract alone.

Figure 7  .

Figure 7  

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Effect of spermidine on inhibition of the mucous secreting layer induced by cigarette smoking in intact (A) and ulcerated (B) rats. Both intact and ulcerated rats (24 hours after ulcer induction) were exposed to cigarette smoke (0, 2, or 4%) for one hour each day for three days. Spermidine was administered intragastrically (100 mg/kg) before each exposure to cigarette smoke. Values are mean (SEM) of 7-8 rats. **p<0.01 v 0% exposure; ††p<0.01 v 4% alone.

Figure 8  .

Figure 8  

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Effect of spermidine on the delay in ulcer healing induced by cigarette smoking, four days after ulcer induction. Twenty four hours after ulcer induction rats were exposed to cigarette smoke (0, 2, or 4%) for one hour each day for three days. Spermidine was administered intragastrically (100 mg/kg) before each exposure. Values are mean (SEM) of 7-8 rats. **p<0.01 v 0% exposure; ††p<0.01 v 4% alone.

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