Corrosive ingestion remains a worldwide public health problem. To date, there are no specific medications with approved efficacy in reducing gastrointestinal injury progression following corrosive ingestion.

The current study assessed the efficacy of N-acetylcysteine (NAC) and vitamin B complex as adjuvant therapy in improving the outcome of patients with corrosive ingestion.

The study included 92 patients with acute corrosive ingestion admitted to Alexandria Poison Center. Patients were distributed into four equal-sized groups and managed as such; Group I received the standard treatment protocol. The other three groups received IV antioxidants in addition to the standard treatment; Group II received NAC, Group III received vitamin B complex, and Group IV received both NAC and vitamin B complex. To assess occurrence of delayed complications, barium swallow and meal were done 21 days after acute corrosive ingestion, and every patient was followed up for one year.

Start of oral intake was earliest among patients in Group II, and as a result, the need for parenteral nutrition decreased significantly with a subsequent decrease in duration of hospitalization. The highest percentage of patients showing normal findings of barium swallow and meal was among the two groups that received NAC (72.7% in Group II and 77.8% in Group IV). Group IV patients who received NAC and vitamin B complex had no esophageal strictures with improved outcomes.

NAC and vitamin B complex enhanced recovery in the acute stage, in addition to prevention of delayed complications, especially esophageal strictures.

Acute corrosive ingestion is associated with high morbidity because of its catastrophic presentation and lifelong complications.This study was conducted on 92 patients admitted to Alexandria Poison Center (APC).IV NAC significantly decreased the time needed for starting oral intake after acute corrosive ingestion and consequently, the need for parenteral nutrition and duration of hospitalization.No patients suffered from esophageal strictures in the group which received both IV NAC and vitamin B complex.Both NAC and vitamin B complex improved the outcome of patients after ingestion of corrosives whether acids or alkalis.

Esophageal strictures in children that develop as a result of accidental ingestion of corrosive substances remain an important health problem. The purpose of this study is to determine the effects of Hesperidin, an effective bioflavonoid in the proliferative and exudative phase of inflammation, on the stricture formation in corrosive esophageal burns.

Experimental esophageal burns in rats were created using a modified Gehanno and Guedon model with 20% NaOH. Rats were divided into 5 groups. In the Sham group, the distal esophagus was prepared and cannulated according to the model, but no NaOH was administrated. The esophageal burn was created with NaOH in the other groups. The burned groups were divided into two groups as untreated (T¹⁴, T²¹) and treated with 100 mg/kg/day Hesperidin (H¹⁴, H²¹) intraperitoneally, and these groups were divided into two according to their sacrification periods (14 and 21 days). Inflammation, fibrosis, and necrosis were graded by histopathological evaluation in all groups. The efficacy of treatment was evaluated using the weight of rats, stenosis index, and histopathological parameters.

Histopathologic damage scores such as inflammation, necrosis, and fibrosis were lower in the H¹⁴ and H²¹ groups and higher in the T¹⁴ and T²¹ groups. And also stenosis index was found higher in T¹⁴ and T²¹ groups (p < 0.05), while it was similar to the Sham group in H¹⁴ and H²¹ groups. No statistically significant difference was found between the H¹⁴ and H²¹ groups in terms of stenosis index. When weights of the rats at the beginning and end of the experiment were compared, weights of the H¹⁴ and H²¹ groups and the Sham group were similar. There was a significant decrease in the weight of the rats in the T¹⁴ and T²¹ groups (p < 0.001).

This study is the first to use Hesperidin in preventing esophageal damage in an esophageal caustic burn model. It was shown that Hesperidin was effective in reducing macroscopic and microscopic histopathologic damage in the corrosive esophageal burn model, preventing the stricture formation, and has positive effects on nutrition in rats with an esophageal burn.

Esophageal burns due to ingestion of corrosive substances are frequently seen in both children and adults. However, there is no standard method of treatment to prevent associated mortality and morbidity. Therefore, this study aimed to evaluate the effects of known antioxidants, namely N-acetyl cysteine and ethyl pyruvate, on esophageal damage due to sodium hydroxide-induced corrosive burns.

Thirty-five female rats were randomly assigned to five equal groups. Group 1 was the sham group, while Group 2 was the control group. Group 3 received N-acetyl cysteine, Group 4 received ethyl pyruvate, and Group 5 received both N-acetyl cysteine and ethyl pyruvate. Rats in the "burn" groups were gavage-fed with 0.2mL of 25% NaOH. All esophagi were extracted on day 4 for histopathological evaluation.

Total histopathological damage scores were evaluated at the end of the study. Groups 3 and 5 were significantly different from the control group in terms of total histopathological scores (p = 0.001), while no significant difference was seen with Group 4. Stenosis index results in groups 3 and 5 were similar to those seen with total histopathological scores (p = 0.004).

N-acetyl cysteine, alone or in combination with ethyl pyruvate, may be useful in the treatment of esophageal damage associated with corrosive substances and in achieving histopathological improvement in an experimental setting.

Caustic esophageal burn is still an important health problem in pediatric surgery. Although there are a number of experimental and clinical studies to increase the recovery of the esophagus and reduce the stenosis rate, there is no consensus on the treatment protocol. Platelet-rich plasma (PRP) is an autologous blood product, which has positive effects on wound healing, reepithelization and scar prevention. The aim of our study was to investigate the effects of PRP on stricture formation and oxidative status after caustic esophageal injury in rats.

Twenty-one rats were divided into three groups [Sham operation (n = 8), corrosive esophageal burn with 30% NaOH (n = 6), topical PRP application after corrosive burn (n = 7)]. On the postoperative 21st day, oxidative markers were measured in the serum, and collagen accumulation and stenosis index were measured histopathologically to assess the efficacy of PRP treatment.

Postoperative weight was higher than preoperative weight in Sham and PRP groups, but lower in the Burn group (p < 0.05). No difference was observed between Sham and PRP groups at total antioxidant status and paraoxonase values, but a significant decrease was found in the Burn group. Group PRP had higher total oxidant status and arylesterase levels than Group Burn (p < 0.05). There was no difference in total thiol values between PRP and Sham group. Histopathological scoring for muscularis mucosa damage revealed a significant reduction in Group PRP, compared to Group Burn (p < 0.05). Esophageal wall thickness and SI were reduced, and luminal diameter was increased in Group PRP compared to Group Burn (p < 0.05).

For the first time in the literature, these results indicate that topical PRP treatment after the experimental corrosive burn has a positive effect on oxidative stress, mucosal healing and decreased stricture development. PRP may be an alternative at the clinical treatment because it can be used during diagnostic esophagoscopy.

Treatment study Level I (randomized controlled trial).

The aim of this study is to evaluate the anti-inflammatory and anti-fibrotic effects of halofuginone in caustic esophageal burn injury in rats.

Corrosive esophageal injury (CEI) was produced in male Wistar albino rats by instilling NaOH solution (1 ml, 37.5%) into the distal esophagus. Rats were decapitated on the 3rd day (early group) or 28th day (late group), and treated daily with either saline or halofuginone (100 µg/kg/day; i.p.), continued on alternate days after the third day. Histopathological evaluation and measurement of nitric oxide (NO), peroxynitrite (ONOO-) and oxygen-derived radicals by chemiluminescence (CL) were made in the distal 2 cm of the esophagus. Non-irrigated proximal esophageal samples were assessed for the levels of nuclear factor (NF)-κB, caspase-3, glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) activity.

GSH, MDA, NF-κB and caspase-3 levels, and MPO activity in the proximal esophagus were not different among groups. Increased number of TUNEL (+) cells in the irrigated esophagus of the early and late caustic injury groups was reduced by halofuginone treatment. High microscopic damage scores in both early and late CEI groups were decreased with halofuginone treatment. NO, ONOO- and CL levels, which were elevated in the saline-treated early CEI group, were reduced by halofuginone treatment, but reduced NO and ONOO- levels in the late period of saline-treated group were increased by halofuginone.

In addition to its anti-fibrotic effects, current findings demonstrate that halofuginone exerts antioxidant and anti-apoptotic actions and supports therapeutic potential for halofuginone in CEI-induced oxidative stress.

The ingestion of caustic substances remains an important public health issue worldwide. Children represent 80% of the ingestion injury population globally. Accidental alkaline material accounts for most caustic ingestions. There is no conclusive evidence of tissue damage and stricture protection of a nasogastric-tube with a solid dilator in the literature, therefore it was hypothesized that early intraesophageal tube placement does not cause additional histopathologic damage and prevents strictures.

An exploratory study on experimental caustic esophageal burns in a rabbit model was designed. In the treated group a silicone tube was placed immediately after causing the burns, while the untreated group followed the natural course of the burn. On the twenty-secondday, an esophagectomy was performed on all animals for microscopic (Histopathologic Damage Score and Stenosis Index) and macroscopic analysis.

Forty animals were randomly divided into two groups. The Histopathologic Damage Score was 3.7±1.1 in the treated group versus 3.9±1.2 in the untreated group (p=.9690). The Stenosis Index was 0.6±0.1 in treated rabbits versus 2.3±0.2 in untreated (p<.0001).

The early placement of an intraesophageal tube with solid dilator prevents stenosis formation and does not produce greater tissue damage.

Corrosive esophageal injuries are one of the life-threatening morbidities leading to esophageal stricture and perforation affecting all age groups but especially children due to accidental ingestions in this age group. Glucagon-like peptide-2 (GLP-2) is an intestinal polypeptide with potent anti-inflammatory effects. Its effects are studied in various studies but not in corrosive esophagitis. We aimed to investigate whether it has protective effect in experimental corrosive esophagitis, in the absence of existing studies into possible links. Twenty-four Wistar-albino rats, weighing 220-240 g, were randomized into three groups (n = 8 in each). First group is control, second one is sham operated, and the third one is treatment group. Median laparotomy was made in all groups. In sham and treatment groups, esophagus was loosened and suspended from 1 cm proximal to the esophageal junction. The esophagus segment between suspenders was exposed to 0.1 mL 5% NaOH for 10 seconds. In the treatment group, rats were given GLP-2 for 7 days intraperitoneally. After 7 days, all rats were sacrified and esophagi were totally removed. In the histopathologic examination, esophageal tissues were compared in terms of inflammation, muscularis mucosa injury, and collagen deposition of tunica muscularis. Histopathologic changes in the esophageal tissues of groups were compared. Histopathologic injury in the GLP-2 treated group was significantly less than sham group (P < 0.05). There was statistically significant healing in the GLP-2 treatment group. It is concluded that GLP-2 has a preventive effect on inflammation and collagen accumulation in an experimental corrosive esophagitis. In the light of the information that initial lesions in the early phase are predictors of complications, GLP-2 is a promising agent that has an anti-inflammatory effect in caustic injuries.

Caustic ingestion continues to be a significant problem worldwide especially in developing countries. In 2008 over 200,000 exposures to caustic substances were reported to the National Poison Data System. The presence or absence of symptoms or oral lesions does not predict the existence or severity of lesions. The best predictor of morbidity and mortality is the extent of injury as assessed during initial evaluation. Upper endoscopy remains the mainstay diagnostic modality for the evaluation of patients with caustic ingestion. There is a pressing need for noninvasive diagnostic modalities and effective therapeutic options to evaluate and treat the complications associated with caustic ingestion.

After ingestion of caustic material, tissue damage is caused by reactive oxygen species and reactive nitrogen species such as peroxynitrite. Mercaptoethylguanidine (MEG) is a well-known scavenger of peroxynitrite. This study was designed to determine whether MEG has a beneficial effect on caustic esophageal injury.

Forty-five rats were allocated into 3 groups: sham-operated, untreated, and treated groups. Caustic esophageal burn was created by instilling 15% NaOH in the distal esophagus. The rats were left untreated or treated with 10 mg/kg per day MEG intraperitoneally for 5 days. All rats were killed at 28 days. Efficacy of the treatment was assessed both histopathologically and biochemically.

Of 15 rats, 6 (40%) died in the untreated group, and only 1 (7%) rat died in the treated group. The stenosis index (SI) and the histopathologic damage score were significantly lower in the MEG treatment group than the untreated group, which showed a correlation with tissue hydroxyproline level. In the untreated group, tissue oxidative stress parameters (malondialdehyde and protein carbonyl content) were significantly higher; and antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) were significantly lower. Administration of MEG ameliorated oxidative stress parameters and antioxidant enzyme activities. Urinary nitrate and nitrite levels increased in the treated and untreated groups in the first 3 days, suggesting increased nitrosative stress; but at the fourth day, nitrate and nitrite level reached control values in the treated group.

Peroxynitrites play an important role in the healing process of caustic esophagitis. As a peroxynitrites scavenger, MEG potentially might be a useful adjuvant agent in the treatment of esophageal caustic burn by modulating the antioxidant defense mechanism.

To investigate the optimal concentration of sodium hydroxide (NaOH) on esophageal stricture formation in rats to establish an animal model of benign esophageal stricture (BES).

Corrosive esophageal burn was produced by internal application of different concentrations of NaOH to the distal esophagus in rats. As much as 66 male rats were randomly divided into eight groups: Group A (control, n = 6), Group B (sham-operated group, n = 6), Group C (5% NaOH, n = 8), Group D (10% NaOH, n = 8), Group E (20% NaOH, n = 8), Group F (30% NaOH, n = 10), Group G (40% NaOH, n = 14), and Group H (50% NaOH, n = 6). Surviving rats were killed at 28 days. The survival rate, body weight gain, symptoms, and histopathological changes were assessed.

The mortality rate was high in Groups G and H (73 and 67%). The prevalence of symptoms of BES was 43% in Groups D and E, 50% in Group F, 75% in Group G, and 100% in Group H. Statistically significant stricture formation of the esophagus was observed in Groups F and G. The degree of tissue damage was significantly higher in Groups E, F, and G.

A high concentration of NaOH of 30% was required to establish a survivable BES model in rats.

The aim of this study was to investigate the efficacy of ibuprofen on the healing of esophagus and the prevention of stricture development after esophageal caustic injuries in rats.

Rats were divided into three groups as: group 1(sham), group 2(esophageal burn injury), group 3(injury + ibuprofen). In groups 2 and 3, a standard esophageal burn injury was created by applying 10% NaOH solution to distal esophagus of about 3 cm. To rats in the sham group, isotonic solution was given instead of NaOH. Ibuprofen (90 mg/kg/day) was given via oral route to group 3 rats. Normal saline as placebo was given via the same route to rats in groups 1 and 2. 28 days later, all the live rats were killed. The distal esophageal segments of all rats were removed and divided into two equal parts for biochemical and histopathologic examination. In the tissue samples, biochemically hydroxyproline and histopathologically collagen content and stenosis indices were evaluated for efficacy of treatment.

The hydroxyproline level (microg/mg wet tissue) in the groups was 1.54 +/- 0.08, 4.82 +/- 0.60, and 3.28 +/- 0.27, respectively. The hydroxyproline level increased significantly in group 2 compared with group 1 (P < 0.01). Although the hydroxyproline level was significantly increased in group 3 compared with group 1, it decreased significantly in group 3 compared with group 2 (P < 0.05) by treatment of ibuprofen. In group 3, the collagen content score (1.50 +/- 0.26) was significantly lower than in group 2 (2.62 +/- 0.37) (P < 0.05). The stenosis index was found as 0.37 +/- 0.02 in group 1, 0.84 +/- 0.02 in group 2, and 0.67 +/- 0.03 in group 3. The stenosis index in group 2 was significantly higher than group 1 and group 3 (P < 0.01). Although the stenosis index was significantly higher than in group 1, a significant decrease in stenosis index was found in group 3 compared with group 2, by ibuprofen treatment (P < 0.01).

Based on these results, we concluded that the treatment with ibuprofen in acute phase esophageal burn injury has beneficial effects on healing of esophagus and may decrease the stricture formation. For these reasons, ibuprofen may effectively be used in the acute phase treatment of caustic esophagus injury and after esophageal dilatation procedures.

An experimental study was carried out to investigate the efficacy of an anti-inflammatory and antiproliferative agent all-trans retinoic acid (ATRA) and an antioxidant agent zinc sulphate (ZnSO(4)) in the prevention of stricture after caustic esophageal burn in rats.

Esophageal burn was induced using 50% NaOH. Rats were divided into four groups as follows: group A (sham; n = 8), group B (control; n = 8), group C (treated with ATRA; n = 8) and group D (treated with ZnSO(4); n = 8). All rats were killed on the 28th day and esophageal tissues were evaluated for histopathologic damage score, hydroxyproline (HP) content and TGF-beta1 expression.

Significant difference was detected in terms of histopathologic damage score between groups B and C (p = 0.002). Although mean HP levels of groups C and D were lower than group B, statistical comparison was not significant. TGF-beta1 expression in group C was significantly lower than group B.

Zinc has not been found effective in the prevention of stricture formation. The results indicate that ATRA has a preventive effect in the development of fibrosis in an experimental model of caustic esophageal burns in rats.

An experimental study was conducted to investigate the role of oxidative stress and effects of erythropoietin (EPO) on methotrexate-induced esophageal damage.

Twenty-four female Sprague-Dawley rats were equally divided into 3 groups: Sham operation animals (group S) were administered subcutaneous injections of 0.2 mL of 0.9% NaCl; control animals (group MTX) were administered subcutaneous injections of methotrexate (5 mg/kg) and EPO-treated animals (group EPO) were administered subcutaneous injections of methotrexate (5 mg/kg) and EPO (2000 IU/kg) once daily for 4 consecutive days. At the fifth day, the distal 1.5-cm esophageal segments were harvested for biochemical and histologic investigations. Oxidative damage was assessed by measuring the levels of malondialdehyde and nitric oxide, and activities of superoxide dismutase and catalase in homogenized samples of esophageal tissue. Histologic damage to esophageal tissue was scored and total tissue damage scores were calculated.

Malondialdehyde levels in the S and EPO groups were significantly lower than those in the MTX group (P<0.05). Catalase and superoxide dismutase activities, and nitric oxide levels in the S and EPO groups were significantly higher than those in the MTX group (P<0.05). Esophageal tissue damage was significantly less in the EPO group than that in the MTX group (P<0.05).

Free radicals elevate in methotrexate given rats' esophagus and EPO has significant preventive effects on methotrexate-induced oxidative damage of esophagus in a rat model.

An experimental study was conducted to investigate the effects of erythropoietin on the acute phase of esophageal burn damage induced by sodium hydroxide.

A standard esophageal alkaline burn was produced by the application of 10% sodium hydroxide to the distal esophagus in an in vivo rat model. Fifty-six female rats were allocated into three groups: Group BC (baseline control, n = 8) rats were uninjured and untreated, Group PC (positive control, n = 24) rats were injured but untreated and Group EPO (erythropoietin-treated, n = 24) rats were injured and given subcutaneous erythropoietin (1,000 IU/kg per day), 15 min, 24, and 48 h after administration of the NaOH solution. Six animals from Group PC and six from Group EPO were killed at 4, 24, 48, and 72 h after application of NaOH to the esophagus. All of animals in Group BC were killed 4 h after exposure to 0.9% NaCl. Oxidative damage was assessed by measuring levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of superoxide dismutase (SOD) and catalase (CAT) in homogenized samples of esophageal tissue. Histologic damage to esophageal tissue was scored by a single pathologist blind to groups.

MDA levels in the BC and EPO groups were significantly lower than those in the PC group (p < 0.05). CAT and SOD activities, and NO levels in the BC and EPO groups were significantly higher than in the PC group (p < 0.05). Esophageal tissue damage measured at 4, 24, 48, and 72 h after NaOH application was significantly less in the EPO group than in the PC group (p < 0.05).

When administered early after an esophageal burn induced by 10% sodium hydroxide in this rat model, erythropoietin significantly attenuated oxidative damage, as measured by biochemical markers and histologic scoring.

Caustic ingestion is one of the most life-threatening events in the pediatric age group, which requires the immediate management and subsequent treatment of its most significant complication, i.e. alterations in esophageal structure. We investigated whether melatonin could reduce the esophageal burn damage induced by sodium hydroxide. It was assumed that melatonin could be effective because of its function as a direct free radical scavenger, its antioxidative actions and its ability to diminish tissue hydroxyproline (HP) levels. Esophageal burns were induced in male rats by the administration of 10% sodium hydroxide. Lipid peroxidation (LPO) products were then measured at the following times: 0, 1, 6, 24, 48 and 72 hr after treatment. Tissue HP concentrations in the injured area were assessed at 14 days after the administration of sodium hydroxide. The groups received either systemic melatonin or normal saline. There were two, non-ischemic, sham control groups treated with or without melatonin. LPO products, malondialdehyde (MDA) and 4-hydroxyalkenal (4-HDA), increased immediately after the administration of sodium hydroxide; this indicates the participation of free radicals in the development of damage. Melatonin diminished the oxidative response and the amount of HP in the late phase of the lesion. Melatonin reduced oxidative damage in the early phase of the esophageal burns induced by sodium hydroxide.

Ozone has been proposed as an antioxidant enzyme activator, immunomodulator and cellular metabolic activator. This study was designed to investigate the efficacy of ozone therapy in the prevention of esophageal damage and stricture formation developed after esophageal caustic injuries in the rat.

Forty-five rats were allocated into three groups; sham-operated, un-treatment and treatment groups. Caustic esophageal burn was created by instilling 15% NaOH in the distal esophagus. The rats were left untreated or treated with 1 mg/kg/day ozone intraperitoneally. All rats were sacrificed at 28 days. Efficacy of the treatment was assessed by measuring the stenosis index (SI) and histopathologic damage score, and biochemically by determining tissue hydroxyproline content (HP), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) and protein carbonyl content (PCC) in esophageal homogenates.

Whereas seven (47%) rats died in the un-treatment group, all rats in the sham-operated and the treatment group survived during the study. SI, the histopathologic damage score, was significantly lower in the ozone-therapy group than the un-treatment group. HP levels were significantly higher in the un-treatment group than the group treated with ozone. Caustic esophageal burn increased MDA and PCC levels and also decreased SOD and GPx enzyme activities. In contrast, ozone therapy decreased the elevated MDA and PCC levels and also increased the reduced SOD and GPx enzyme activities.

Ozone has a preventive effect in the development of fibrosis by decreasing tissue damage and increasing the antioxidant enzyme activity in an experimental model of corrosive esophageal injury.

The enzyme poly(adenosine diphosphate-ribose) polymerase affects the repair of DNA in damaged cells. However, its activation in damaged cells can lead to adenosine triphosphate depletion and death. This study was designed to investigate the efficacy of 3-amino benzamide (3-AB), a poly(adenosine diphosphate-ribose) polymerase inhibitor, on the prevention of esophageal damage and stricture-formation development after esophageal caustic injuries in rat.

Forty-five rats were allocated into 3 groups: sham-operated, untreated, and treated groups. Caustic esophageal burn was created by instilling 15% NaOH to the distal esophagus. The rats were left untreated or treated with 3-AB 10 mg/kg per day intraperitoneally. All rats were killed on the 28th day. Efficacy of the treatment was assessed by measuring the stenosis index and histopathologic damage score and biochemically by determining tissue hydroxyproline content, superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), and protein carbonyl content (PCC) in esophageal homogenates.

Treatment with 3-AB decreased the stenosis index and histopathologic damage score seen in caustic esophageal burn rats. Hydroxyproline level was significantly higher in the untreated group as compared with the group treated with 3-AB. Caustic esophageal burn increased MDA and PCC levels and also decreased SOD and GPx enzyme activities. On the contrary, 3-AB treatment decreased the elevated MDA and PCC levels and also increased the reduced SOD and GPx enzyme activities.

3-Amino benzamide has a preventive effect in the development of fibrosis by decreasing tissue damage and increasing the antioxidant enzyme activity in an experimental model of corrosive esophagitis in rats.

The aim of the study reported here was to evaluate the biochemical and histopathologic effects of omeprazole and vitamin E in rats with corrosive esophageal burns. A total of 144 Wistar Albino rats were divided into 12 experimental groups (12 rats per group) and used in an animal study. Group I rats were given a laparotomy and received no treatment (control group), while groups II, III and IV received a laparotomy and were treated with omeprazole, vitamin E or omeprazole/vitamin E, respectively. Groups V-XII rats received a laparotomy and were given a caustic acid burn through acid instillation (1 ml caustic 10% sulphuric acid; groups V-VIII) or alkali instillation (corrosive 10% sodium hydroxide solution; groups IX-XII) into the isolated esophageal segment via a 22-Fr cannula for 2 min. Each group of rats subjected to caustic burn received either no treatment (groups V and IX) or were treated with omeprazole, vitamin E or omeprazole/vitamin E, respectively (remaining six groups). Omeprazole (20 mg/kg) or vitamin E (10 mg/kg) was administered to the rats intraperitoneally or intramuscularly, respectively. Seventy-two rats (50% of each group, n = 6) were killed immediately after the experimental treatment (acute phase). The remaining rats were kept under standard conditions for 21 days (late phase) before being killed. The distal esophageal segments were harvested from all animal and used in histopathologic and biochemical analyses. Compared to the controls (no caustic burn), rats receiving only the acid or alkali installation (and no subsequent treatment) had the highest mean malondialdehyde (16.9 and 15.8 micromol MDA/g protein, respectively) and hydroxyproline (5.9 and 5.7; mg HP/g wet tissue) levels of all groups. In comparison, rats treated with acid + omeprazole and/or vitamin E had relatively lower MDA (12.9 and 11.6 micromol/g protein, respectively) and HP levels (4.3 and 4.08 mg/g wet tissue, respectively). Similarly, rats treated with alkali + omeprazole and/or vitamin E had low levels of MDA (13.9 and 11.7 micromol/g protein, respectively) and HP (4.3 and 4.4 mg/g wet tissue, respectively). The glutathione (GSH) levels of acid-only- or alkali-only-treated rats were lower than those found in omeprazole- and/or vitamin E-treated rats. Based on these results, we conclude that vitamin E and omeprazole affect the biochemical and histopathologic parameters in rats receiving corrosive esophageal burn from acid and alkali. The effect of both substances was slightly greater in the acid-treated groups.

The purpose of medical treatment in the caustic esophageal burns (CEB) is to decrease inflammatory reaction and to prevent stricture formation. Resveratrol has anti-inflammatory and antifibrotic properties. The aim of this study is to investigate potential therapeutic effects of resveratrol in experimental CEB. We divided 42 male Wistar albino rats into five groups: a control group, caustic groups 4 and 28 (esophageal burns were created), and resveratrol groups 4 and 28 (esophageal burns were created and resveratrol was administered). We used 25% NaOH to form CEB following the method of Gehanno and Guedon as modified by Liu and Richardson. Animals were killed on the 4th and 28th days for biochemical and histopathological examinations. We found that the mean malondialdehyde and nitric oxide assays of the caustic groups were significantly higher than that of the resveratrol groups (P < 0.05). On the other hand, glutathione assay of the resveratrol groups was significantly higher than that of the caustic groups (P < 0.05). Histologically, edema, inflammation and necrosis were found to be significantly lower in the resveratrol 4 group compared with the caustic 4 group (P < 0.05). Submucosal and muscular collagen accumulation were found significantly lower in the resveratrol 28 group compared with the caustic 28 group (P < 0.05). We conclude that resveratrol decreased both the inflammatory reaction and the stricture formation in experimental CEB.

An experimental study was conducted to investigate the effects of allopurinol, which inhibits the enzyme xanthine oxidase, on oxidative stress and on the prevention of stricture development after esophageal caustic injuries in rat. A randomized controlled study was conducted and 60 Wistar albino rats were divided into 6 equal groups, three groups for the acute phase and 3 groups for the chronic phase. Caustic esophageal burn was created by application of 37.5% NaOH to the distal esophagus. Allopurinol was administered at 40 mg/kg daily. Efficacy of the treatment for the acute phase was assessed by measuring tissue malondialdehyde (MDA), nitric oxide (NO) and glutathione (GSH) at the 3rd day; and for the chronic phase by determining tissue hydroxyproline content and histopathologic damage score at the 28th day. We found an increase in XO, MDA and GSH levels and a decrease in NO levels in the acute phase. Allopurinol reinstated the increase in XO significantly, while MDA, GSH and NO levels were reinstated insignificantly. There was no significant difference in means of tissue hydroxyproline content. Histopathologic damage scores were significantly lower in the allopurinol treated group. This study, which is to our knowledge, the first in the literature investigating the influence of allopurinol on caustic esophageal burn, reveals that allopurinol effects MDA, GSH and NO levels insignificantly in the acute phase of caustic esophageal burn and decreases fibrosis significantly in the chronic phase.

In 2004, the American Association of Poison Control Centers' Toxic Exposure Surveillance System documented over 200,000 exposures to caustic substances, in both household and industrial products. Although the most commonly affected body areas are the face, eyes, and extremities, all reported fatalities were as a result of ingestion. Little controversy exists in patient management following dermal or ocular caustic exposure. Immediate water irrigation of the site of caustic exposure, followed by routine burn care, analgesia, intravenous fluids, and electrolyte replacement are standards of care. In this manuscript, a thorough review of the management of gastrointestinal caustic exposure is explored, not only because of the high rates of morbidity and mortality associated with these exposures, but also because there remains controversy regarding appropriate management of such exposures. Hydrofluoric acid, a weak acid in its aqueous form, requires special consideration and specific antidotes, and as such, is addressed separately.

Acute esophageal necrosis, which presents as a black esophagus on endoscopy, is a rare disorder that is poorly described in the medical literature. In this study, we analyze all cases reported to date to define risk factors, clinical presentation, endoscopic features, histologic appearance, treatment, complications, outcome and etiopathogenesis of the disease and to describe a distinct medical syndrome and propose a staging system.

We searched Medline and PubMed from January 1965 to February 2006 for English-language articles using the key words "acute esophageal necrosis," "necrotizing esophagitis," and "black esophagus."

A total of 88 patients were reported in the literature during the 40 years, 70 men and 16 women with an average age of 67 years. Patients were generally admitted for gastrointestinal bleeding and cardiovascular event/shock. Patients presented with hematemesis and melena in more than 70% of the cases. Upper endoscopy showed black, diffusely necrotic esophageal mucosa predominantly affecting the distal third of the organ. Necrosis was confirmed histologically in most cases. Complications included strictures or stenoses, mediastinitis/abscesses, and perforations. Overall mortality was 31.8%.

This study provides a structured approach to identifying risk factors, diagnosis, and pathogenesis of the acute esophageal necrosis. Risk factors include age, male sex, cardiovascular disease, hemodynamic compromise, gastric outlet obstruction, alcohol ingestion, malnutrition, diabetes, renal insufficiency, hypoxemia, hypercoagulable state, and trauma. Mechanism of damage is usually multifactorial secondary to ischemic compromise, acute gastric outlet obstruction, and malnutrition. Overall, acute esophageal necrosis should be viewed as a poor prognostic factor, associated with high mortality from the underlying clinical disease.

This study was evaluated to investigate the efficacy of caffeic acid phenethyl ester (CAPE), which is a natural honeybee product exhibits a spectrum of biological activities including anti-microbial, anti-inflammatory, antioxidant and anti-tumoral actions, on the prevention of stricture development after esophageal caustic injuries in the rat.

Thirty healthy male Wistar albino rats were utilized in this study. The rats were randomly allotted into one of three experimental groups: group A (sham) animals were uninjured. Caustic esophageal burn was created by applying 1 ml 37.5% NaOH to the distal esophagus. Group B rats were injured but untreated. Group C rats were injured and received CAPE (10 micromol/kg/day i.p. for 28 days). Efficacy of the treatment was assessed by measuring the esophageal transit time, stenosis index, histopathologic damage score and biochemically by determining tissue hydroxyproline content, lipid peroxidation and antioxidant enzyme activities.

The esophageal transit time, the stenosis index, histopathologic damage score and the hydroxyproline level were significantly increased in the untreated group compared with the sham and CAPE-treated groups. Treatment with CAPE decreased tissue hydroxyproline levels, histological damage, and the stenosis index, but except the esophageal transit time. Caustic esophageal burn also increased the lipid peroxidation and decreased the antioxidant enzyme activities in the untreated group. CAPE treatments decreased the elevated lipid peroxidation and also increased the reduced antioxidant enzyme activities. In corrosive esophageal burn group with no treatment, the most consistent findings were degenerative changes and increased in submucosal collagen content, and the luminal narrowing. CAPE treatment protected esophagus. Nevertheless, there was the slight increase in submucosal collagen.

It is concluded that CAPE has a preventive effect on the stricture development after esophageal caustic injuries in the rat.

This study was evaluated to investigate the efficacy of Ebselen, which is an organoselenium compound and glutathione peroxidase mimic, on the prevention of stricture development after esophageal caustic injuries in the rat.

Thirty healthy male Wistar albino rats were utilized in this study. The rats were randomly allotted into one of three experimental groups: group A (sham) animals were uninjured. Caustic esophageal burn was created by applying 1 ml of 37.5% NaOH to the distal esophagus. Group B rats were injured but untreated. Group C rats were injured and received Ebselen (10 mg/kg/day) via the oral route. Blood and tissue samples for the biochemical and histopathological analysis were taken all rats at the end (28th day) of the experiment. Oxidative stress is believed to play a role in the pathogenesis of corrosive esophageal burns. To assess changes in the cellular antioxidant defense system, we measured the activities of antioxidant enzymes (such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD), and catalase (CAT)) in esophagus homogenates. We also measured esophageal tissue malondialdehyde (MDA) levels, a marker of lipid peroxidation, to determine whether there is an imbalance between oxidant and antioxidant status. Efficacy of the treatment was assessed by measuring the stenosis index and histopathologic damage score and biochemically by determining tissue hydroxyproline content, lipid peroxidation and antioxidant enzyme levels.

The stenosis index in group B was significantly increased compared with group A and C (P<0.05). The hydroxyproline level was significantly increased in group B compared with group A and C (P<0.05). In group B, the histopathologic damage score was significantly higher than in group C (P<0.05). Treatment with Ebselen decreased tissue hydroxyproline levels, histological damage, and the stenosis index. Caustic esophageal burn increased the lipid peroxidation and also decreased the antioxidant enzyme levels in group B. Ebselen treatments for 28 days decreased the elevated lipid peroxidation and also increased the reduced antioxidant enzyme levels. Live weights of the rats was significantly decreased in group B compared with group A and C (P<0.05).

It is concluded that Ebselen has a preventive effect in the development of fibrosis and decrease the lipid peroxidation, and increase the antioxidant defense system activity in an experimental model of corrosive esophagitis in rats.

Previous experimental studies have suggested that administration of antithrombotic, antioxidant, and cytoprotective agents have protective effects in caustic injury of the esophagus. Therefore, an experimental study was carried out to investigate the effects of iloprost, a stable analogue of prostacyclin, on the esophagus after caustic burns. Sixty Wistar albino rats were divided into three groups of 20 animals each. In group A, animals were uninjured and untreated. In group B, animals were injured but untreated. In group C, rats were injured and administered intravenous iloprost for 3 days. Caustic esophageal burn was produced by 1 ml of 15% NaOH. Efficacy of the treatment was assessed by measuring the tissue malondialdehyde (MDA), superoxide dismutase, and glutathione levels with biochemical methods on the 3rd postoperative day. Histopathological evaluation was done on the 28th postoperative day. The level of MDA was significantly increased in group B compared with the other groups. In group B, the histopathological damage score was significantly higher than in groups A and C. There was also a significant difference between groups A and C regarding the histopathologic damage. These results indicate that iloprost has a preventive effect in experimental caustic esophageal burn in rats.

Stricture formation is a late complication of caustic esophageal burn, which is a common problem in childhood. For this reason, this experimental study was designed to observe the possible effect of nitric oxide on healing and fibrosis formation in caustic esophageal burns.

The rats were divided into five groups. Group A (n=12) received sham burn and treatment with saline injection. Group B (n=34) received caustic burn. Rats in group C (n=31), were given water supplement with 10 g/L L-arginine that was started 24 h preoperatively and continued until postoperative day 4. In group D (n=21), S-methylisothiourea (SMT, specific inducible nitric oxide synthase (iNOS) inhibitor), was injected at a dose of 3 mg/kg i.p. at 30 min before caustic burn, and similar dose was reinjected immediately after caustic burn. SMT 6 mg/kg/day injections continued for 4 days long. In group E (n=22), Nomega-nitro-L-arginine (L-NNA, nonspecific nitric oxide synthase (NOS) inhibitor) was injected at a dose of 15 mg/kg i.p. at 30 min before caustic burn, and similar dose was reinjected immediately after caustic burn. L-NNA 30 mg/kg/day continues for 4 days.

Dead rates were significantly higher in group E than in groups A-D. The mean hydroxyproline levels in esophageal tissue were significantly lower in groups A and B than in group D. Histopathologically, tissue damage scores in the esophageal tissue were higher in group D than in groups A-C.

Inhibition of iNOS with SMT was impaired in wound healing due to caustic esophageal burn and provoked collagen accumulation at a later period. Those effects may due to inhibition of antioxidant, immunomodulatory and antifibrotic effects of NO.

The aim of this study was to investigate the efficacy of trimetazidine (TMZ), an antioxidant agent, on the prevention of stricture development after esophageal caustic injuries in rat.

Thirty rats were divided into 3 equal groups. A standard esophageal caustic burn was produced by application of 37.5% NaOH for a period of 90 seconds followed by water rinse. Group A (sham) animals were uninjured. Group B rats were injured but untreated. Group C rats were injured and received TMZ (5 mg/kg/d) via intraperitoneal route. Efficacy of the treatment was assessed in 28 days by measuring stenosis index and histopathologic damage score and by determining tissue hydroxyproline content.

The stenosis index in the TMZ-treated group was significantly lower than the untreated group, similarly in the sham laparotomy group (stenosis index: 0.34 +/- 0.10, 0.94 +/- 0.21, 0.38 +/- 0.05, respectively; P < .05). The hydroxyproline level (microgram per milligram of wet tissue) was significantly lower in the TMZ-treated group compared with untreated group, similarly in the sham laparotomy group (1.06 +/- 0.14, 1.33 +/- 0.08, 0.68 +/- 0.15 microg/mg wet tissue, respectively; P < .05). In the untreated group, histopathologic damage score was significantly higher than TMZ-treated group (P < .05).

Trimetazidine reduces the degree of fibrosis and ameliorates histopathologic damage in experimental model of corrosive esophagitis in rats.

Corrosive esophageal burn is a common health problem in the pediatric age group and causes serious esophageal injuries. The medical treatment in acute phase of corrosive esophageal injury is of particular importance for prevention of esophageal stricture. We therefore aimed to investigate the possible beneficial effect of trapidil (triazolopyrimidine), an inhibitor for phosphodiesterase and platelet-derived-growth-factor, during acute phase of esophageal corrosive injury. Wistar albino rats were randomly allocated to untreated, treated, and sham-operated groups (n = 10 for each group). Corrosive esophageal burn was generated with 10% NaOH solution. The rats were left untreated (untreated group) or treated with trapidil as a single dose of 40 mg/kg intraperitoneally after one hour of the injury (treated group). Abdominal esophageal segment was isolated and tied in sham-control group. The studied esophageal segment was removed from each animal after 24 hours. Malondialdehyde (MDA) and nitric oxide (NO) levels were measured in the esophageal tissues. The ulcer depth was graded by histopathologic examination. MDA and NO levels were significantly higher in the untreated group than in the treated group. Namely, trapidil treatment significantly decreased MDA and NO levels in the injured tissues, the levels of which are similar to those in the tissues of control animals. The grades of ulcer depth were significantly improved in the treated group. These results indicate that the reactive oxygen radicals increase in the early phase of corrosive esophagitis and cause tissue damage. We suggest that trapidil treatment may be useful in acute phase of corrosive esophageal injury.

The authors aimed to find out the roles of free oxygen radicals, nitric oxide (NO), and endothelin (ET) in caustic injury of rat esophagus.

Forty-five Wistar albino rats were used to form 6 groups. The study groups are summarized as 1, sham (S; n = 7); 2, sham + L-arginine (SA; n = 7); 3, sham + L-NAME (SN; n = 7); 4, injury (I; n = 8); 5, injury + L-arginine (IA; n = 8); 6, injury + L-NAME (IN; n = 8). Normal saline in the sham groups and 50% NaOH in the caustic injury groups were administered to the distal esophagus. Free oxygen radicals and NO were detected by chemiluminescence from tissue samples, and they were correlated with histologic examinations. Tissue ET was measured also with immunohistochemistry.

The injury was verified histologically. Free oxygen radical levels were found to be increased as well as NO and ET with the caustic injury (P <.05). L-arginine caused a histologic increase in the injury that was close to statistical significance (P =.08). L-NAME showed no significant effect.

Free radicals, NO, and ET increase in the early phase of caustic esophageal injury. Understanding their early interactions during the caustic injury may help in future therapeutic strategies.

Caustic esophageal burn is a serious problem in pediatric surgery. Even though many clinical and experimental studies had been performed, the complication rate could not be reduced to a satisfying level. In this study, the authors evaluated the effects of hyperbaric oxygen (HBO) therapy in caustic esophageal burn in rats.

Rats were divided into 4 groups, and caustic burn at the distal esophagus was created by applying 50% NaOH for 3 minutes in all groups. The first and third groups did not receive HBO therapy. HBO therapy was applied to the second group for 2 days and to the fourth group for 28 days. To evaluate the effects of short-term HBO therapy, the first 2 groups were compared for ulceration, inflammation, and submucosal vascular thrombosis after 2 days. The third and fourth groups were compared for the long-term effects of HBO therapy. Rats in these groups were killed after 28 days and compared for the collagen content, weight, and mortality rate.

In the second group, which received 2 days of HBO therapy, ulcer depth and vascular thrombosis were significantly lower than these in the first group (P =.022 and P =.020, respectively). The fourth group, which received 4 weeks of HBO therapy, had a significantly reduced mortality rate, weight loss, and collagen score and hydroxyproline level if compared with the third group (P =.035; P =.016; P =.028; and P =.033, respectively).

These results indicate that HBO therapy is useful in caustic esophageal burn both in short-term and long-term use.

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.

A 6-year-old boy developed respiratory distress, metabolic acidosis, severe esophageal and gastric burns, and a coagulopathy after ingestion of an unknown volume of methyl ethyl ketone peroxide (MEKP) in dimethyl phthalate. He was discharged from the pediatric intensive care unit 19 days postingestion but subsequently developed a stricture of the gastroesophageal junction and complete fibrosis of the middle third of the stomach, necessitating gastric resection and reconstruction. He was discharged 93 days postingestion on a program of dilation for the residual esophageal stricture. MEKP acts by initiating lipid peroxidation via free radical production that results in cellular dysfunction and death. Acetylcysteine, a glutathione precursor and possible free radical scavenger, may be of use in severe MEKP poisoning. This case demonstrates the severe effects that some industrial chemicals can have both systemically and locally at the point of contact with the gastrointestinal tract, as well as the long-term management required to ensure good quality of life.