epidermal-growth-factor and Esophageal-Stenosis

An experimental study was performed to modify the healing response in caustic esophageal burns to prevent stricture development. Two different agents with different modes of actions, caffeic acid phenethyl ester (CAPE) and epidermal growth factor (EGF), were studied. CAPE has antiinflammatory, immunomodulatory, antioxidant, and antimitotic properties. EGF has known properties in supporting wound healing and in protecting esophagus from injuries.. The model described by Gehanno and its modification by Liu was used to create standard esophageal burns with 50% NaOH. The study was performed with 76 rats in 4 main groups (sham, CAPE, EGF, and control) and 2 subgroups in each for 5 and 28 days of observation. Efficacy of treatment was assessed in 28-day subgroups by measuring weight gain, contrast esophagograms on day 27, histologic evaluation by measuring stenosis index (wall thickness/lumen diameter), and collagen deposition, and biochemically by determining tissue hydroxy proline (OHP) content.. In the end of the study, increase rates of mean body weights of the animals in the 28-day subgroups were as follows: sham, 30%; CAPE, 23%; EGF, 22%; and control, 14%. Although all the animals in subgroups significantly gained weight, the mean weight gain was significantly low in controls when compared with sham, CAPE, and EGF groups (P <.05). Contrast esophagograms on day 27 showed no stenosis in the sham, mild stenosis in CAPE and EGF, and severe stenosis with proximal dilatation in controls. Stenosis indices of the subgroups were as follows: sham, 0.29; CAPE, 0.41; EGF, 0.41; control, 0.84. Index was significantly higher in controls (P <.05). Collagen accumulation scores in the esophageal wall were as follows: Sham, 0.0; CAPE, 0.87; EGF, 0.30; control, 2.70. Scores also were significantly higher in controls (P <.05). Tissue (OHP) levels were as follows (mg/g dry tissue): Sham, 1.48; CAPE, 1.53; EGF, 1.90; control, 4.01. Production of OHP was significantly higher in controls.. The results of the parameters in the study indicate that administration of CAPE and EGF has beneficial effects in the prevention of caustic esophageal strictures. Those effects of CAPE may occur through its antiinflammatory, immunomodulatory, and antioxidant properties, and EGF may occur through its induced proliferative properties on the esophagus.

Topics: Animals; Burns, Chemical; Caffeic Acids; Epidermal Growth Factor; Esophageal Stenosis; NF-kappa B; Phenylethyl Alcohol; Random Allocation; Rats; Rats, Wistar; Wound Healing

Effects of sequential use of epidermal growth factor followed by interferon gamma on healing response after severe oesophageal corrosive burns has been demonstrated. This sequential treatment improves the inflammatory response of the initial phase and prevents residual stenosis. The aim of this study was to evaluate the use of interferon gamma alone in the same condition.. The study was performed in 5 groups (n = 15) of Wistar rats: control, placebo, epidermal growth factor alone, interferon gamma alone and epidermal growth factor for 5 days followed by interferon gamma from the 6th to 20th day. The last 4 groups had an oesophageal injury caused by a solution of 2.5 N NaOH. The efficacy of treatment was assessed on days 2, 5 and 20 on: weight gain, oesophageal internal lumen, stenosis index: wall thickness/lumen diameter, collagen production.. Interferon gamma significantly reduced residual stenosis frequency while it did not improves the initial healing process. A complete effect on the two healing phases was only observed in animals having the sequential treatment.. These results could lead to clinical trial in man to evaluate efficacy of sequential treatment with epidermal growth factor-interferon gamma in oesophageal corrosive burns.

Topics: Animals; Body Weight; Burns, Chemical; Caustics; Drug Therapy, Combination; Epidermal Growth Factor; Esophageal Stenosis; Hydroxyproline; Interferon-gamma; Male; Rats; Rats, Wistar

Human epidermal growth factor (EGF), a small polypeptide (6 kDa) with mitogenic properties, has been implicated in the protection of gastrointestinal mucosal integrity. The efficacy of EGF in the prevention and healing of sclerotherapy-induced esophageal lesions was investigated in 24 minipigs with surgically induced portal hypertension. In addition, the effect of EGF on intragastric acidity and pharmacokinetics was investigated as possible means to explain its protective mechanism of action. The animals underwent three weekly sessions of sclerotherapy with polidocanol 2% and were concomitantly and for an additional three weeks treated with either placebo or EGF administered paravenously in the esophagus and/or subcutaneously. The subcutaneous treatment with EGF significantly (P < 0.05) reduced esophageal stricture and scar formations associated with sclerotherapy. Gastric pH values were significantly (P < 0.01) elevated only in animals receiving subcutaneous injections of EGF. Furthermore, the subcutaneous administration of EGF was associated with unexpected prolonged plasma concentration of the peptide. These results suggest a possible clinical value of EGF as an adjunctive treatment with the sclerotherapy.

Topics: Animals; Epidermal Growth Factor; Esophageal Diseases; Esophageal Stenosis; Gastric Juice; Humans; Hydrogen-Ion Concentration; Male; Polidocanol; Polyethylene Glycols; Recombinant Proteins; Sclerosing Solutions; Sclerotherapy; Swine; Swine, Miniature; Ulcer

A study was performed to attempt to modify the healing response to severe oesophageal corrosive burns to prevent complications. The study was performed on four groups each of 15 Wistar rats: a control group, an untreated group and groups given epidermal growth factor (EGF) alone or EGF for 5 days and interferon (IFN) gamma from the sixth to 20th day. In the last three groups an oesophageal lesion was induced with 2.5 mol l-1 sodium hydroxide solution. The efficacy of treatment was assessed on days 2, 5 and 20 by measurement of weight gain, oesophageal internal lumen, stenosis index (wall thickness: lumen diameter) and collagen production. On day 5, collagen synthesis was significantly (P < 0.05) higher in rats given EGF than in the untreated group. On day 20, no significant difference was seen in weight gain between the control rats and either treated group and stenoses were present in all untreated rats and in none of the treated group. The stenosis index on day 20 was lower in the groups given EGF and EGF-IFN-gamma than in untreated rats (P < 0.05) and collagen production was significantly (P < 0.05) lower in the group given EGF and IFN-gamma than in the other animals. The sequential use of EGF and IFN-gamma significantly reduced the frequency of residual stenosis.

Topics: Animals; Burns, Chemical; Collagen; Drug Therapy, Combination; Epidermal Growth Factor; Esophageal Stenosis; Esophagus; Hydroxyproline; Interferon-gamma; Male; Random Allocation; Rats; Rats, Wistar; Sodium Hydroxide; Weight Gain; Wound Healing

Human epidermal growth factor (EGF), a naturally occurring protein, has been implicated in the protection of gastrointestinal mucosal integrity. The efficacy of EGF in the prevention of sclerotherapy-induced esophageal lesions was investigated in 18 minipigs with surgically induced portal hypertension. The animals underwent five weekly sessions of sclerotherapy with polidocanol 2% and were concomitantly treated with either placebo or EGF administered either paravenously or subcutaneously. EGF significantly (P < 0.05) reduced esophageal ulcerations, stricture formations, and mucosal histological damage associated with sclerotherapy. The drug was well-tolerated with no overt toxicity. These results suggest a potentially important clinical value of EGF as an adjunctive treatment with the sclerotherapy.

Topics: Animals; Epidermal Growth Factor; Esophageal Diseases; Esophageal Stenosis; Esophagoscopy; Female; Mucous Membrane; Recombinant Proteins; Sclerotherapy; Swine; Swine, Miniature; Ulcer