Oral administration of synthetic human urogastrone promotes healing of chronic duodenal ulcers in rats

doi:10.1016/0016-5085(86)90867-X

Gastroenterology

Volume 90, Issue 4, April 1986, Pages 911-917

https://doi.org/10.1016/0016-5085(86)90867-X Get rights and content

Abstract

The effect of oral administration of synthetic human epidermal growth factor/urogastrone (EGF/URO) on healing of chronic duodenal ulcers induced by cysteamine in rats was investigated and compared with that of cimetidine, a H₂-receptor antagonist. After 25 and 50 days of treatment, synthetic human EGF/URO significantly increased healing of chronic duodenal ulcers to the same extent as cimetidine. Combined treatment with synthetic human EGF/ URO and cimetidine for 25 days was more effective than synthetic human EGF/URO given alone, whereas combined treatment for 50 days was significantly more effective than cimetidine alone. These results show that a combination of an agent inhibiting gastric acid secretion and the cytoprotective and growth-stimulating peptide EGF/URO seems to be more effective with regard to duodenal ulcer healing than individual administration of the two substances. Synthetic human EGF/URO is a potent inhibitor of gastric acid secretion when administered intravenously, but had no effect on acid secretion when given intraduodenally, which suggests that the effect of synthetic human EGF/URO is a direct action on the duodenal mucosa. In conclusion, this study showed that oral synthetic human EGF/URO has a significant effect on healing of duodenal ulcers in rats. The amount of synthetic human EGF/URO administered is comparable to that found in saliva during stimulation of the salivary glands. Our results, therefore, suggest that EGF/URO is one of the endogenous factors participating in healing of duodenal ulcers.

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Local effects of epidermal growth factor on the wound healing in esophageal anastomosis: An experimental study
2017, International Journal of Pediatric Otorhinolaryngology
Citation Excerpt :
It has been reported that EGF also has a significant role in the healing of the intestinal mucosa [13–15]. Of all specific articles related to EGF, the effect of EGF on acute and chronic wound healing showed that the promising effect for enhanced acute wound healing but had been accused of due to the limited impact on chronic wound healing and a connection between invasive neoplasm [16]. In anywhere of the body, the process of wound healing occurs in three stages: inflammation, proliferation, and remodeling, respectively [17].
In this study with the experimental model of primary repair of esophageal atresia(EA), we investigated the effects of the epidermal growth factor(EGF) on wound healing in the anastomosis of EA.
Forty rabbits that were performed a resection of a 1-cm segment of the cervical esophagus followed by the end-to-end anastomosis were divided into four groups. Group I (7-day group) and III (21-day group), the control groups, had no EGF applied to the anastomosis. In group II (7-day group) and group III (21-day group), all around the anastomoses were locally covered with 100 μg/kg EGF. Group 1, 2 and 3, 4 were sacrificed on the 7th and 21st day, respectively. We investigated and compared with bursting pressure, vascularization around the anastomotic line by histopathology, inflammation, and fibroblast granulation as well as hydroxyproline level by biochemical.
No significant difference was found at vascularization and inflammation between all of the groups (p > 0.05). Considering the critical parameters of the groups, at bursting pressure difference was found between group 1 and 2 as well as 3 and (p < 0.05). At fibroblast granulation and hydroxyproline level, no difference was found between group 1 and 2 (p > 0.05) but the difference between group 3 and 4 (p < 0.05).
EGF might be useful in preventing anastomotic leakage of esophageal atresia in primary anastomosis of esophageal atresia by accelerating wound healing process and increasing the stability of the anastomotic line.
Effects of epidermal growth factor on atrophic enteritis in piglets induced by experimental porcine epidemic diarrhoea virus
2008, Veterinary Journal
Epidermal growth factor (EGF) promotes gastrointestinal mucosal recovery by stimulating the mitogenic activity of intestinal crypt epithelial cells. The aim of this study was to determine the effects of EGF on atrophic enteritis induced in piglets by experimental infection with porcine epidemic diarrhoea virus (PEDV) strain Dr13. Two groups of 12 conventional, colostrum-deprived, 1-day-old, large White-Duroc cross breed piglets were inoculated orally with PEDV (3 × 10⁵ 50% tissue culture infective doses), with or without EGF (10 μg/kg/day, intraperitoneally once daily for 4 days after infection) and compared to 12 uninfected, untreated control piglets.
PEDV + EGF piglets had less severe clinical signs than PEDV only piglets at 48 and 60 h post-infection (hpi). Histologically, the ratio of villous height:crypt depth of PEDV + EGF piglets was significantly higher than PEDV only piglets at 36 and 48 hpi. Immunohistochemistry for Ki67 demonstrated increased proliferation in intestinal crypt epithelial cells of PEDV + EGF piglets compared to PEDV only piglets at 36, 48 and 60 hpi. EGF stimulates proliferation of intestinal crypt epithelial cells and promotes recovery from atrophic enteritis in PEDV-infected piglets.
Stimulation by theophylline and sildenafil of rat submandibular secretion of protein, epidermal growth factor and flow rate
2003, Pharmacological Research
In the present study, the effects of cAMP- and cGMP-phosphodiesterase (PDE) inhibitors, theophylline, and sildenafil on secretion of protein, amylase and epidermal growth factor (EGF) and the flow rate from rat submandibular saliva were examined in an acute experiment. Theophylline at doses of 25, 50, 85 mg kg⁻¹ and sildenafil at doses of 1, 2, 5 mg kg⁻¹ were administered intraperitoneally 2 h before saliva collection. Pure submandibular saliva was collected intraorally by microployethylene tubes under anesthesia using dissecting microscope.
Theophylline at doses of 25, 50, 85 mg kg⁻¹ increased salivary flow rate to 197% (P<0.01), 186% (P<0.01), and 209% of control, respectively. Sildenafil at doses of 1, 2, 5 mg kg⁻¹ also increased flow rate to 232% (P<0.01), 182% (P<0.01), and 197% of control, respectively. Theophylline at doses of 25, 50, 85 mg kg⁻¹ increased total protein concentration to 98% (P<0.01), 84% (P<0.01), and 210% of control, respectively. Sildenafil at doses of 2 and 5 mg kg⁻¹ increased total protein concentration to 75% (P<0.01), and 240% of control, respectively. Theophylline at dose of 85 mg kg⁻¹ increased EGF concentration to 60% (P<0.01) of control. Sildenafil at doses of 2 and 5 mg kg⁻¹ increased EGF concentration to 44% (P<0.05) and 90% (P<0.01) of control, respectively. No statistically significant change was observed in amylase activity by administration of theophylline or sildenafil. The present results indicate that increasing intracellular levels of cAMP and cGMP have stimulatory effects on salivary functions. Regarding beneficiary effects of increased salivary flow rate and secretion of EGF in maintaining oral health, theophylline and sildenafil may find good places in some oral diseases.
Effects of epidermal growth factor microemulsion formulation on the healing of stress-induced gastric ulcers in rats
2002, Journal of Controlled Release
Citation Excerpt :
The studies have demonstrated that EGF is also capable of protecting the gastric mucosa from damage caused by various irritants, such as aspirin [10] or cysteamine [11]. EGF has also been reported to accelerate the healing process of chronic gastric [12] and duodenal ulcers [13]. Microscopic evaluation of gastric mucosa samples revealed that the best recovery was obtained in the ME+EGF treated group.
The effects of intragastric (i.g.) administration of microemulsion formulation of epidermal growth factor (EGF) on the healing of acute gastric ulcers induced by cold-restraint stress in rats was studied and compared with intraperitoneal (i.p.) administration of solutions. In the microemulsion formulation (W/O), labrafil M 1944 CS was the oil phase. Arlacel 186 and Brij 35 were used as the surfactants. Absolute alcohol and distilled water were used as the co-surfactant and the aqueous phase, respectively. Acute gastric lesions were induced by cold-restraint stress for 4 h in the refrigerator (4.0±0.5 °C). EGF was administered at a dose of 6 μg/kg per day intraperitoneally and intraperitoneally for 7 days. Basal gastric acid secretion (μequiv. H⁺/30 min), ulcer score (mm²) and tissue mucus levels (μg/g tissue) were measured. Basal gastric secretion was significantly reduced after the administration of EGF microemulsion (ME+EGF) (P<0.05). There was no significant decrease in basal gastric acid secretion following i.p (IPEGF) and i.g (IG-EGF) of EGF administrations of solutions compared to their control groups (P>0.05). The results indicate that the highest reduction in the basal acid secretion was seen after the administration of a microemulsion of EGF formulation. The mean ulcer score was reduced by i.g treatment with the microemulsion dosage form of EGF in 7 days from 15.9±1.4 to 1.16±0.45 mm² and was almost completely healed in four of the animals. The results demonstrate that the ulcer score was significantly reduced in i.p. (IPEGF) solution (P<0.005), i.g (IG-EGF) solution (P<0.01) and i.g. microemulsion (ME+EGF) (P<0.01) treated groups compared to untreated group. In IG-EGF, ME+EGF treated groups, mucus levels increased significantly compared to their control groups(P<0.05 and P<0.01). In contrast, there was no significant change in the mucus levels following i.p. EGF administration (P>0.05).
Immunoreactive epidermal growth factor receptors are present in gastrointestinal epithelial cells of preterm infants with necrotising enterocolitis
2001, Early Human Development
Introduction: Epidermal growth factor (EGF) affects epithelial cell proliferation, differentiation and migration in the gastrointestinal tract of experimental animals, and increases proliferation when given intravenously to children with congenital microvillous atrophy or necrotising enteritis. The aim of the present study is to determine whether EGF receptors (EGFR) are present in the gut epithelium of preterm infants, and to discover whether neonatal necrotising enterocolitis (NEC) is associated with the absence of EGFR from mucosal cells. Methods: Tissues were taken from involved colon and small intestine of four preterm infants with NEC, and control tissues were taken from four other neonates who had laparatomies for congenital malformations. Sections of the tissues were examined histopathologically after treatment with a monoclonal antibody against the external domain of the EGFR (Zymed Laboratories, San Francisco, CA, USA). Results: Histopathological examination confirmed diagnosis of NEC in the involved bowel and controls showed appearance within normal limit. Immunoreactive EGFR were present on the epithelial cells of both the colon and small intestine, localised on the basolateral membrane of the cells of both subject and the controls. There was no apparent reduction in expression compared with controls. Conclusion: NEC in preterm infants is not associated with absence of EGFR. The presence of EGFR in gut epithelial cells raises the possibility of using EGF for prophylaxis or treatment of NEC.
Epidermal growth factor accelerates pancreatic recovery after caerulein- induced pancreatitis
2000, European Journal of Pharmacology
We examined the influence of endogenous and exogenous epidermal growth factor (EGF) on pancreatic repair after acute pancreatitis. Caerulein-induced pancreatitis was evoked in rats with intact or removed salivary glands and EGF (10 μg/kg) was administered starting 24 h after cessation of caerulein infusion. The dose of EGF 10 μg/kg was chosen because it was the most effective in preliminary experiments when 1, 10 or 50 μg/kg of EGF was used. Caerulein administration caused acute edematous pancreatitis with biochemical and histological manifestation of pancreatic damage, followed by spontaneous regeneration. The effect of salivectomy on the course of acute pancreatitis was slight, resulting in additional reduction in pancreatic blood flow, DNA synthesis and in an increase in plasma interleukin 1β level. Treatment with EGF accelerated the healing of pancreatic damage, causing an increase in pancreatic blood flow and DNA synthesis. EGF caused faster normalization of plasma amylase and lipase activity and plasma interleukin 1β concentration, as well as, this peptide accelerated the restoration of pancreatic amylase activity. On histological examination, EGF caused reduction of pancreatic damage and acceleration of tissue repair. We conclude that EGF reduces the severity of pancreatic damage evoked by caerulein-induced pancreatitis-related pancreatic damage and accelerates tissue repair. The beneficial effects of EGF appear to depend, at least in part, on the improvement of pancreatic blood flow, as well as on an increase of pancreatic cell growth and limitation of the activation cytokine release.

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^*

This work was supported in part by grants from the Danish Medical Research Council (12-4680), the Danish Hospital Foundation for Medical Research, Region of Copenhagen, The Faroe Islands and Greenland (49/83), and the NOVO Foundation.

Synthetic human urogastrone was supplied by G. D. Searle Co., Ltd. and Imperial Chemical Industries PLC, who suggested the use of urogastrone and cimetidine in the cysteamine-induced ulcer model.

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Oral administration of synthetic human urogastrone promotes healing of chronic duodenal ulcers in rats*

Abstract

Gastroenterology

Regul Pept

Gastroenterology

FEBS Lett

Biochim Biophys Acta

Epidermal growth factor-urogastrone, a polypeptide acquiring hormonal status

Vitam Horm

Isolation and structure of urogastrone and its relationship to epidermal growth factor

Nature

Immunohistochemical localisation of urogastrone to human duodenal and submandibular glands

Gut

Epidermal growth factor-like material in rat submandibular gland (1)

Am J Anat

Effect of vasoactive intestinal polypeptide and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands

Gut

Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the tongue, esophagus, and stomach of the adult male mouse

Endocrinology

Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the duodenum, jejunum, ileum, caecum, colon, and rectum of the adult male mouse

Endocrinology

Epidermal growth factor stimulates ornithine decarboxylase activity in the digestive tract of mouse

Effect of mouse epidermal growth factor/urogastrone on the functional maturation of rat intestine

Endocrinology

Adrenergic effects on exocrine secretion of rat submandibular epidermal growth factor

Gut

The role of Brunner's glands in the intrinsic resistance of the duodenum to acid-peptic digestion

Ann Surg

Healing of cysteamine-induced duodenal ulcers in the rat

Dig Dis Sci