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. 2014 Dec 31:10:961.
doi: 10.1186/s12917-014-0303-7.

Protective effects of (1-(4-hydroxy-phenyl)-3-m-tolyl-propenone chalcone in indomethacin-induced gastric erosive damage in rats

Summaya M Dhiyaaldeen  1 , Zahra A Amin  2 , Pouya H Darvish  3 , Iman Fahmi Mustafa  4 , Mazen M Jamil  5 , Elham Rouhollahi  6 , Mahmood A Abdulla  7
Affiliations

Protective effects of (1-(4-hydroxy-phenyl)-3-m-tolyl-propenone chalcone in indomethacin-induced gastric erosive damage in rats

Summaya M Dhiyaaldeen et al. BMC Vet Res. .

Abstract

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) can result in peptic ulcer disease (PUD) which is a common condition worldwide. The aim of this study was to evaluate the antiulcer properties of (1-(4-hydroxy-phenyl)-3-m-tolyl-propenone) (HPTP) chalcone in rats using indomethacin as ulcerogenic agent.

Results: None of the rats showed symptoms of kidney and liver toxicity during the term of the study. Administration of HPTP had decreased the acidity, increased gastric wall mucus and flattening of gastric mucosa and reducing erosive gastric damage area. HPTP also showed dose dependent increase in SOD, GPx activity and PGE2 level and decrease MDA. H & E stain showed decreased infiltration of leucocytes with edema of submucosal layer. PAS staining showed intense uptake of magenta color of gastric wall mucus in rats fed with HPTP, and immunohistochemical staining of gastric mucosa revealed over-expression of HSP70 protein, down-expression of Bax protein and over expression of TGF-β in rats administered with HPTP.

Conclusion: This study has revealed that chalcone1-(4-hydroxy-phenyl)-3-m-tolyl-propenone can serve as a safe and effective antiulcer agent as it has been proved to increase pH and gastric wall mucus, increase GPx, SOD, PGE2, and decrease MDA level, ultimately, it has also contributes towards the over-expression of HSP protein andTGF-β, and down-expression of Bax protein.

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Figures

Figure 1
Figure 1
Effects of HPTP on Histology of liver and kidney in acute toxicity testing. Rats treated with vehicle (1A and 1B), rats treated with 250 mg/kg HPTP (1C and 1D), rats treated with 500 mg/kg HPTP (1E and 1F), rats treated with 1000 mg/kg HPTP (1G and 1H). There were no significant difference in the histology of liver and kidney between treated and control groups (H&E stain) (magnification 20x).
Figure 2
Figure 2
Macroscopic evaluation of the gastric lesions in rats. The normal control group (A) shows no injury of gastric mucosa. The indomethacin treated group (B) produced visible hemorrhagic necrosis of gastric mucosa (black arrow). Rats pre-treated with 50 mg/kg HPTP (C) shows moderate injuries in the gastric mucosa (black arrow) and little flattened (white arrow). Rats pretreated with 100 mg/kg HPTP (D) shows little flattened (white arrow) in gastric mucosa and fewer injuries were observed (black arrow). The omeprazole treated group (E) has more flattened (white arrow) of gastric mucosa and few and small injuries in the gastric mucosa (black arrow).
Figure 3
Figure 3
Effects of HPTP on glutathione peroxidase activity in indomethacin induced erosive gastric damage in rat stomach. Values are expressed as Mean ± S.E.M. (*a) indicates significance at P < 0.05 versus indomethacin with HPTP chalcone and (*) at P < 0.05 versus indomethacin with normal control.
Figure 4
Figure 4
Effect of HPTP on SOD enzyme in indomethacin induced erosive gastric damage in rat stomach. Values are expressed as Mean ± SEM. (*) indicates significance at P < 0.05 versus indomethacin with HPTPchalcone and (*a) at P < 0.05 versus indomethacin with normal control.
Figure 5
Figure 5
Effect of HPTP on Prostaglandin E 2 activity. Values are expressed as Mean ± S.E.M. (*a) indicates significance at P < 0.05 versus indomethacin with HPTP chalcone and (*) at P < 0.05 versus indomethacin with normal control.
Figure 6
Figure 6
Effect of pre-treatment with HPTP and omeprazole followed by indomethacin (100 mg/kg) on Malondialdehyde releasing. Values are expressed as Mean ± S.E.M. (*a) indicates significance at P < 0.05 versus indomethacin with normal control and (*) at P < 0.05 versus HPTP chalcone.
Figure 7
Figure 7
Histological evaluation of gastric lesions in sections stained with Hematoxylin & Eosin (10X). Normal control group (A) has normal tissue epithelium. Indomethacin group (B) shows disruption of surface epithelium with hemorrhage (black arrow) and the lesions infiltrate deep into mucosa layer (white arrow) wide edema (brown arrow) and leukocyte infiltration (red arrow). HPTP pre-treated groups (C & D) shows reduction of submucosal edema (brown arrow), mild to moderate disruption of mucosa epithelium (blue arrow) few infiltration of leukocyte. Omeprazole group (E) shows mild disruption of the surface epithelium (blue arrow), and mild submucosal edema (brown arrow) and bit of leukocyte (H&E stain, magnification 20x).
Figure 8
Figure 8
Histological evaluation of gastric glycoproteins in sections stained with PAS. The magenta color in the apical epithelial cells shows glycoprotein accumulation in the gastric glands (blue arrow). Normal control group (A), indomethacin treated group (B), HPTP pre-treated groups (C & D) and omeprazole pre-treated group (E) (PAS stain, magnification 20x).
Figure 9
Figure 9
Immunohistochmical analysis of HSP70 in gastric tissue induced with indomethacin. (A) Section showed normal mucosal. (B) Section of ulcerated stomach tissue showed down-regulation of HSP70 in injured area (white arrow). Sections (C, D and E) that pre-treated with 50, 100 mg/kg of HPTP and 20 mg/kg of omeprazole respectively showed up-regulation of HSP70 (white arrow) (magnification 20x).
Figure 10
Figure 10
Immunohistochmical analysis of TGF-β protein expression in gastric tissue of rat induced with indomethacin. (A) Section shows normal mucosal area and express regulated of TGF-β (red arrow). (B) Section of ulcerated stomach tissue ashowed down-regulation of TGF-β almost non-existent in injured area (white arrow). Sections (C, D and E) that pre-treated with 50, 100 mg/kg of HPTP and 20 mg/kg of omeprazole respectively found the up-regulation of TGF-β (red arrows) (magnification 20x).
Figure 11
Figure 11
Immunohistochmical analysis of Bax protein expression in gastric tissue of rat induced with indomethacin. (A) Section shows normal mucosal area and express down-regulated of Bax. (B) Section of ulcerated stomach tissue appears up-regulation of Bax protein in injured area (white arrow). Sections (C, D and E) that pre-treated with 50, 100 mg/kg of HPTP and 20 mg/kg of omeprazole respectively found the Bax protein expression was down-regulated (magnification 20x).
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