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Accelerated Ulcer Healing and Resistance to Ulcer Recurrence with Gastroprotectants in Rat Model of Acetic Acid-induced Gastric Ulcer.

Young Oh T, Ok Ahn B, Jung Jang E, Sang Park J, Jong Park S, Wook Baik H, Hahm KB - J Clin Biochem Nutr (2008)

Bottom Line: This study was designed to compare the rates of QOUH achievement in rat gastric ulcer model between acid suppressant treated group and gastroprotectant treated group accompanied with elucidations of molecular mechanisms.Significantly attenuated levels of inflammatory cytokines including IL-2, transforming growth factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), nitrotyrosine were responsible for the resistance to ulcer recurrence in Group III.Conclusively, gastroprotectant might be prerequisite in order to achieve ideal QOUH through significant inductions of remodeling.

View Article: PubMed Central - PubMed

Affiliation: Dong A Pharmaceutical Research Institute, Yongin 130-708, Korea.

ABSTRACT
Quality of ulcer healing (QOUH) is defined as ideal ulcer healing featuring with the fine granular ulcer scar, high functional restoration and the resistance to recurrence. This study was designed to compare the rates of QOUH achievement in rat gastric ulcer model between acid suppressant treated group and gastroprotectant treated group accompanied with elucidations of molecular mechanisms. Serosal injection of acetic acids for generating gastric ulcer and intraperitoneal (ip) injection of recombinant interleukin 1-beta (IL-1beta) for recurring healed ulcer was done in SD rats. The 72 rats were divided into three groups according to treatment as follows; Group I, no further treatment, Group II, 8 weeks treatment of omeprazole, and Group III, 8 weeks of gastroprotectant treatment. IL-1beta was administered for ulcer recurrence after 28 weeks of acetic acid injection. At four weeks after gastric ulcerogenesis, 58.3% (7/12) of active gastric ulcer were converted to healing stage in Group III, but 16.7% (2/12) in Group II and none in Group I, for which significant levels of epidermal growth factor, mucin, and pS2/trefoil peptide1 were contributive to these accelerated healings of Group III. ip injections of rIL-1beta (200 microg/kg) at 28 weeks after acetic acid injection led to 100% of ulcer recurrence in Group I and 75.0% in Group II, but only 16.7% of Group III rats showed ulcer recurrence. Significantly attenuated levels of inflammatory cytokines including IL-2, transforming growth factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), nitrotyrosine were responsible for the resistance to ulcer recurrence in Group III. Conclusively, gastroprotectant might be prerequisite in order to achieve ideal QOUH through significant inductions of remodeling.

No MeSH data available.


Related in: MedlinePlus

Experimental protocol for ulcer healing and ulcer recurrence according to group. Group I denotes the group of rats healed naturally up to 28 weeks after serosal injection of acetic acid, Group II denotes the group of rats treated with 8 weeks of proton pump inhibitor, intraperitoneal injections of omeprazole, and Group III denotes the group of rats receiving 8 weeks of gastroprotectant, DA-9601 in pellet diets. After 28 weeks, all rats were administered with intraperitoneal injections of 200 µg/kg recombinant IL-1β irrespective of group and sacrificed after 48 h later to observe ulcer recurrence. Meanwhile, 12 rats in each group were killed at 4 weeks after acetic acid injection and the remaining 12 rats in each group were sacrificed at 28 weeks after acetic acid injection. Preliminary study confirmed that 28 weeks of duration were enough for complete ulcer healing even without any treatment. The classification of ulcer stage was determined based on the classification of Sakita and Miwa [25] as A (active) stage, H (healing) stage, and S (scarring) stage.
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Related In: Results  -  Collection


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Figure 1: Experimental protocol for ulcer healing and ulcer recurrence according to group. Group I denotes the group of rats healed naturally up to 28 weeks after serosal injection of acetic acid, Group II denotes the group of rats treated with 8 weeks of proton pump inhibitor, intraperitoneal injections of omeprazole, and Group III denotes the group of rats receiving 8 weeks of gastroprotectant, DA-9601 in pellet diets. After 28 weeks, all rats were administered with intraperitoneal injections of 200 µg/kg recombinant IL-1β irrespective of group and sacrificed after 48 h later to observe ulcer recurrence. Meanwhile, 12 rats in each group were killed at 4 weeks after acetic acid injection and the remaining 12 rats in each group were sacrificed at 28 weeks after acetic acid injection. Preliminary study confirmed that 28 weeks of duration were enough for complete ulcer healing even without any treatment. The classification of ulcer stage was determined based on the classification of Sakita and Miwa [25] as A (active) stage, H (healing) stage, and S (scarring) stage.

Mentions: Under the anesthesia with ketamine, the laparotomy was done for acetic acid (40 µl, 10% vol/vol), which was injected to the subserosa of the stomach with micro-syringe to induce gastric ulcer. We tried to induce gastric ulcer in the same area of each stomach in the mid-fundus between the two branches of the main arterial vessel. The abdomen was sutured and the rats were returned to their cages. After operation, the rats were fasted for 48 h more with the supply of intravenous fluid infusion through carotid cannulation catheter and were fed normally thereafter (Fig. 1). To determine the size of ulcers and stages after 4 weeks or 24 weeks after acetic acid injection, animals were killed with an overdose of ether and their stomachs were removed. The stomachs were opened along the greater curvature and rinsed with cold saline. Then the stomachs were pinned to a cork board and then inflated, and the areas (mm2) of the ulcers were determined under a dissecting macroscope (Olympus, Tokyo, Japan) and the classification of ulcer stage was determined based on the classification of Sakita and Miwa [25] as follows; A stage (active stage, A1, the surrounding mucosa is edematously swollen and no regenerating epithelium is seen. A2, the surrounding edema has decreased, the ulcer margin is clear, and slight amount of regenerating epithelium is seen in the ulcer margin), H stage (healing stage, H1, the white coating is becoming thin and the regenerating epithelium is expanding into the ulcer base. The gradient between ulcer margin and the ulcer floor is becoming flat. The diameter of the mucosal defect is about one half to two thirds that of A1; H2, the defect is smaller than in H1 and the regenerating epithelium covers most of ulcer floors and the area of white coating is about a quarter to one third that of A1) and S stage (scarring stage, S, the regenerating epithelium completely covers the floor of ulcer. The white coating has disappeared. Upon close observation, many capillaries can be seen, which is called “red scar” (S1), which become white scar with the reduction of redness, called “white scar” (S2).


Accelerated Ulcer Healing and Resistance to Ulcer Recurrence with Gastroprotectants in Rat Model of Acetic Acid-induced Gastric Ulcer.

Young Oh T, Ok Ahn B, Jung Jang E, Sang Park J, Jong Park S, Wook Baik H, Hahm KB - J Clin Biochem Nutr (2008)

Experimental protocol for ulcer healing and ulcer recurrence according to group. Group I denotes the group of rats healed naturally up to 28 weeks after serosal injection of acetic acid, Group II denotes the group of rats treated with 8 weeks of proton pump inhibitor, intraperitoneal injections of omeprazole, and Group III denotes the group of rats receiving 8 weeks of gastroprotectant, DA-9601 in pellet diets. After 28 weeks, all rats were administered with intraperitoneal injections of 200 µg/kg recombinant IL-1β irrespective of group and sacrificed after 48 h later to observe ulcer recurrence. Meanwhile, 12 rats in each group were killed at 4 weeks after acetic acid injection and the remaining 12 rats in each group were sacrificed at 28 weeks after acetic acid injection. Preliminary study confirmed that 28 weeks of duration were enough for complete ulcer healing even without any treatment. The classification of ulcer stage was determined based on the classification of Sakita and Miwa [25] as A (active) stage, H (healing) stage, and S (scarring) stage.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2386523&req=5

Figure 1: Experimental protocol for ulcer healing and ulcer recurrence according to group. Group I denotes the group of rats healed naturally up to 28 weeks after serosal injection of acetic acid, Group II denotes the group of rats treated with 8 weeks of proton pump inhibitor, intraperitoneal injections of omeprazole, and Group III denotes the group of rats receiving 8 weeks of gastroprotectant, DA-9601 in pellet diets. After 28 weeks, all rats were administered with intraperitoneal injections of 200 µg/kg recombinant IL-1β irrespective of group and sacrificed after 48 h later to observe ulcer recurrence. Meanwhile, 12 rats in each group were killed at 4 weeks after acetic acid injection and the remaining 12 rats in each group were sacrificed at 28 weeks after acetic acid injection. Preliminary study confirmed that 28 weeks of duration were enough for complete ulcer healing even without any treatment. The classification of ulcer stage was determined based on the classification of Sakita and Miwa [25] as A (active) stage, H (healing) stage, and S (scarring) stage.
Mentions: Under the anesthesia with ketamine, the laparotomy was done for acetic acid (40 µl, 10% vol/vol), which was injected to the subserosa of the stomach with micro-syringe to induce gastric ulcer. We tried to induce gastric ulcer in the same area of each stomach in the mid-fundus between the two branches of the main arterial vessel. The abdomen was sutured and the rats were returned to their cages. After operation, the rats were fasted for 48 h more with the supply of intravenous fluid infusion through carotid cannulation catheter and were fed normally thereafter (Fig. 1). To determine the size of ulcers and stages after 4 weeks or 24 weeks after acetic acid injection, animals were killed with an overdose of ether and their stomachs were removed. The stomachs were opened along the greater curvature and rinsed with cold saline. Then the stomachs were pinned to a cork board and then inflated, and the areas (mm2) of the ulcers were determined under a dissecting macroscope (Olympus, Tokyo, Japan) and the classification of ulcer stage was determined based on the classification of Sakita and Miwa [25] as follows; A stage (active stage, A1, the surrounding mucosa is edematously swollen and no regenerating epithelium is seen. A2, the surrounding edema has decreased, the ulcer margin is clear, and slight amount of regenerating epithelium is seen in the ulcer margin), H stage (healing stage, H1, the white coating is becoming thin and the regenerating epithelium is expanding into the ulcer base. The gradient between ulcer margin and the ulcer floor is becoming flat. The diameter of the mucosal defect is about one half to two thirds that of A1; H2, the defect is smaller than in H1 and the regenerating epithelium covers most of ulcer floors and the area of white coating is about a quarter to one third that of A1) and S stage (scarring stage, S, the regenerating epithelium completely covers the floor of ulcer. The white coating has disappeared. Upon close observation, many capillaries can be seen, which is called “red scar” (S1), which become white scar with the reduction of redness, called “white scar” (S2).

Bottom Line: This study was designed to compare the rates of QOUH achievement in rat gastric ulcer model between acid suppressant treated group and gastroprotectant treated group accompanied with elucidations of molecular mechanisms.Significantly attenuated levels of inflammatory cytokines including IL-2, transforming growth factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), nitrotyrosine were responsible for the resistance to ulcer recurrence in Group III.Conclusively, gastroprotectant might be prerequisite in order to achieve ideal QOUH through significant inductions of remodeling.

View Article: PubMed Central - PubMed

Affiliation: Dong A Pharmaceutical Research Institute, Yongin 130-708, Korea.

ABSTRACT
Quality of ulcer healing (QOUH) is defined as ideal ulcer healing featuring with the fine granular ulcer scar, high functional restoration and the resistance to recurrence. This study was designed to compare the rates of QOUH achievement in rat gastric ulcer model between acid suppressant treated group and gastroprotectant treated group accompanied with elucidations of molecular mechanisms. Serosal injection of acetic acids for generating gastric ulcer and intraperitoneal (ip) injection of recombinant interleukin 1-beta (IL-1beta) for recurring healed ulcer was done in SD rats. The 72 rats were divided into three groups according to treatment as follows; Group I, no further treatment, Group II, 8 weeks treatment of omeprazole, and Group III, 8 weeks of gastroprotectant treatment. IL-1beta was administered for ulcer recurrence after 28 weeks of acetic acid injection. At four weeks after gastric ulcerogenesis, 58.3% (7/12) of active gastric ulcer were converted to healing stage in Group III, but 16.7% (2/12) in Group II and none in Group I, for which significant levels of epidermal growth factor, mucin, and pS2/trefoil peptide1 were contributive to these accelerated healings of Group III. ip injections of rIL-1beta (200 microg/kg) at 28 weeks after acetic acid injection led to 100% of ulcer recurrence in Group I and 75.0% in Group II, but only 16.7% of Group III rats showed ulcer recurrence. Significantly attenuated levels of inflammatory cytokines including IL-2, transforming growth factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), nitrotyrosine were responsible for the resistance to ulcer recurrence in Group III. Conclusively, gastroprotectant might be prerequisite in order to achieve ideal QOUH through significant inductions of remodeling.

No MeSH data available.


Related in: MedlinePlus