Insulin-Like Growth Factor I Accelerates Gastric Ulcer Healing by Stimulating Cell Proliferation and by Inhibiting Gastric Acid Secretion

Nonsteroidal anti-inflammatory drugs elevate gastric acid secretion, possibly contributing to their ability to interfere with gastric ulcer healing. Inhibitors of cyclooxygenase-2 have been shown to delay experimental gastric ulcer healing. In the present study, we tested the hypothesis that cyclooxygenase-2-derived prostaglandins modulate gastric acid secretion. Studies were performed in normal rats and in rats with iodoacetamide-induced gastritis. Inflammation in the latter group was confirmed histologically and by a threefold increase in tissue levels of the granulocyte marker myeloperoxidase and was also associated with overexpression of cyclooxygenase-2 in the stomach. Basal acid secretion in both groups of rats was not affected by pretreatment with DuP-697, a selective inhibitor of cyclooxygenase-2. A nonselective cyclooxygenase inhibitor, indomethacin, had no effect on acid secretion in normal rats but caused a doubling of acid secretion in the rats with gastritis. DuP-697 had no effect on pentagastrin-induced secretion in either group of rats. Gastritis itself was associated with significantly increased pentagastrin-induced acid secretion, and this was further increased in rats pretreated with indomethacin. These results suggest that in a setting of gastric inflammation, prostaglandins derived from cyclooxygenase-1, not cyclooxygenase-2, exert inhibitory effects on acid secretion.

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Reduction of EGF is associated with the delay of ulcer healing by cigarette smoking

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2000.278.1.g10 ◽

2000 ◽

Vol 278 (1) ◽

pp. G10-G17 ◽

Cited By ~ 28

Author(s):

L. Ma ◽

W. P. Wang ◽

J. Y. C. Chow ◽

S. T. Yuen ◽

C. H. Cho

Keyword(s):

Cell Proliferation ◽

Gastric Ulcer ◽

Growth Factor ◽

Gastric Mucosa ◽

Cigarette Smoking ◽

Mrna Expression ◽

Salivary Glands ◽

Cigarette Smoke ◽

Ulcer Healing ◽

Gastric Ulcer Healing

Cigarette smoking is associated with peptic ulcer diseases. Smokers have lower levels of salivary epidermal growth factor (EGF) than nonsmokers. We investigated whether reduction of EGF is involved in the delay of gastric ulcer healing by cigarette smoking. Rats with acetic acid-induced ulcers were exposed to cigarette smoke (0, 2, or 4% vol/vol) 1 day after ulcer induction. EGF level was elevated 1 day after ulcer induction in salivary glands and serum, and 4 days after ulcer induction in the gastric mucosa. However, cigarette smoke depressed these beneficial effects and EGF mRNA expression in salivary glands and gastric mucosa. Cigarette smoke delayed gastric ulcer healing and reduced cell proliferation, angiogenesis, and mucus synthesis. Exogenous EGF (10 and 20 μg/kg iv) before smoke exposure reversed the adverse effects of cigarette smoke, whereas vascular endothelial growth factor level and nitric oxide synthase activity were unaffected. It is concluded that the detrimental effect of cigarette smoke on ulcer healing is a consequence of reduction of angiogenesis, cell proliferation, and mucus secretion through the depressive action on EGF biosynthesis and its mRNA expression in salivary glands and gastric mucosa.

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Accelerated gastric ulcer healing in thyroxine-treated rats: roles of gastric acid, mucus, and inflammatory response

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2017-0399 ◽

2018 ◽

Vol 96 (6) ◽

pp. 597-602 ◽

Cited By ~ 4

Author(s):

Olasupo S. Adeniyi ◽

Benjamin O. Emikpe ◽

Samuel B. Olaleye

Keyword(s):

Gastric Ulcer ◽

Acid Secretion ◽

Gastric Acid ◽

Ulcer Healing ◽

Gastric Mucus ◽

Gastric Ulcer Healing ◽

Neutrophil Lymphocyte Ratio ◽

Ulcer Area ◽

Thyroxine Treatment ◽

Male Wistar Rats

The roles of gastric acid, mucus, and inflammation on the pro-ulcer-healing effect of thyroid hormone were investigated. Male Wistar rats were randomly divided into four groups: control, thyroidectomised, thyroidectomised with thyroxine treatment (100 μg·kg–1·day–1), and sham-operated animals treated with thyroxine. Thirty-five days after thyroidectomy, sham surgery, or thyroxine treatment, an ulcer was experimentally induced. Healing was assessed 3, 7, and 10 days post-ulceration by measurement of the ulcer area, gastric mucus and acid secretion, and neutrophil lymphocyte ratio (NLR) as an index of inflammation. By day 10, the ulcer area had decreased in all groups. Recovery was significantly greater (P < 0.05) in thyroxine-treated rats (78.5% ± 1.6% reduction in ulcer area) than in controls (72.3% ± 1.2% reduction) or thyroidectomised rats (63.3% ± 1.9% reduction). Thyroxine-treated animals also had the highest reduction in NLR (65.0% ± 2.5%). Mucus secretion was significantly lower (P < 0.05) in thyroidectomised rats by days 3 and 7. Furthermore, by day 10, the concentration of basal acid decreased by 77.4% ± 2.6% in thyroxine-treated, 65.0% ± 0.0% in control, and 51.5% ± 3.3% in thyroidectomised rats. We conclude that thyroxine accelerates gastric ulcer healing by altering mucus and acid secretion and reducing NLR.

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