The protective effect of dapsone against ethanol-; stress-; and indomethacin-induced gastric erosion in rats
Abstract
Several factors contribute to the development of gastric erosions, including corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, and stress. These factors can cause or worsen gastrointestinal ulcers by activating inflammatory pathways or by altering gastric mucosal blood flow. Dapsone is an antimicrobial compound with anti-inflammatory properties. The aim of this study was to evaluate the protective effects of dapsone against gastric erosions-induced by alcohol, stress, or indomethacin. Gastric damage was induced in male rats in different three experimental models: ethanol (5 ml/kg, p.o.)-, water-immersion stress-, and indomethacin (30 mg/kg, p.o.)- induced ulcer. Rats in each of these three experimental models were divided into 5 groups: Normal group, 2. Control group (gastric damage + vehicle), 3. Gastric damage+ dapsone 1 mg/kg, 4. Gastric damage+ dapsone 3 mg/kg, 5. Gastric damage+ dapsone 10 mg/kg. In this study, the J- score ulcer index and histopathological assessment were performed. In addition, inflammatory cytokines levels, NF-κB expression and MPO activity were determined. Dapsone reduced the tissue injuries and erosion area in all three experimental groups compared to the control group. In addition, serum levels of inflammatory cytokines, TNF-alpha and IL-1β were reduced in the dapsone treatment groups. The expression of NF-κB and tissue concentration of myeloperoxidase (a marker of neutrophil activation) was also reduced in rats given dapsone. To conclude, dapsone exhibits significant protective effects against the development of experimental gastric erosions in rats and these effects seem to be related to its anti-inflammatory and antioxidant properties.
1. Malfertheiner P, Chan FK, McColl KE. Peptic ulcer disease. The Lancet. 2009;374(9699):1449-61.
2. Susser M, Stein Z. Civilisation and peptic ulcer. The Lancet. 1962;279(7221):116-9.
3. Huang J-Q, Sridhar S, Hunt RH. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis. The Lancet. 2002;359(9300):14-22.
4. Piper JM, Ray WA, Daugherty JR, Griffin MR. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Annals of internal medicine. 1991;114(9):735-40.
5. Chou SP. An examination of the alcohol consumption and peptic ulcer association—Results of a national survey. Alcoholism: Clinical and Experimental Research. 1994;18(1):149-53.
6. Ramakrishnan K, Salinas RC. Peptic ulcer disease. American family physician. 2007;76(7).
7. Collier DS, Pain J. Non-steroidal anti-inflammatory drugs and peptic ulcer perforation. Gut. 1985;26(4):359-63.
8. Warzecha Z, Ceranowicz P, Dembinski M, Cieszkowski J, Ginter G, Ptak-Belowska A, et al. Involvement of cyclooxygenase-1 and cyclooxygenase-2 activity in the therapeutic effect of ghrelin in the course of ethanol-induced gastric ulcers in rats. J Physiol Pharmacol. 2014;65(1):95-106.
9. Warzecha Z, Dembiński A, Ceranowicz P, Konturek SJ, Tomaszewska R, Stachura J, et al. Inhibition of cyclooxygenase-2 reduces the protective effect of hepatocyte growth factor in experimental pancreatitis. European journal of pharmacology. 2004;486(1):107-19.
10. Brzozowski T, Konturek P, Konturek S, Pajdo R, Schuppan D, Drozdowicz D, et al. Involvement of cyclooxygenase (COX)-2 products in acceleration of ulcer healing by gastrin and hepatocyte growth factor. Journal of Physiology and Pharmacology. 2000;51(4, 1).
11. Sørbye H, Svanes K. The role of blood flow in gastric mucosal defence, damage and healing. Digestive Diseases. 1994;12(5):305-17.
12. Hollander D, Tarnawski A, Krause WJ, Gergely H. Protective effect of sucralfate against alcohol-induced gastric mucosal injury in the rat: macroscopic, histologic, ultrastructural, and functional time sequence analysis. Gastroenterology. 1985;88(1):366-74.
13. Oates PJ, Hakkinen JP. Studies on the mechanism of ethanol-induced gastric damage in rats. Gastroenterology. 1988;94(1):10-21.
14. Plummer MP, Blaser AR, Deane AM. Stress ulceration: prevalence, pathology and association with adverse outcomes. Critical Care. 2014;18(2):213.
15. Lanas A, Chan FK. Peptic ulcer disease. The Lancet. 2017;390(10094):613-24.
16. Mahmood A, Al-Bayaty F, Salmah I, AB NS, Harita H. Enhancement of gastric ulcer by Areca catechu nut in ethanol-induced gastric mucosal injuries in rats. Journal of Medicinal Plants Research. 2011;5(12):2462-9.
17. Suzuki H, Nishizawa T, Tsugawa H, Mogami S, Hibi T. Roles of oxidative stress in stomach disorders. Journal of clinical biochemistry and nutrition. 2011:1112080129-.
18. Soll AH. Pathogenesis of peptic ulcer and implications for therapy. New England Journal of Medicine. 1990;322(13):909-16.
19. Farrar J, Hotez PJ, Junghanss T, Kang G, Lalloo D, White NJ. Manson's Tropical Diseases E-Book: Expert Consult-Online and Print: Elsevier Health Sciences; 2013.
20. Wozel G, Blasum C. Dapsone in dermatology and beyond. Archives of dermatological research. 2014;306(2):103-24.
21. Lewis AJ, Gemmell DK, Stimson WH. The anti-inflammatory profile of dapsone in animal models of inflammation. Agents and actions. 1978;8(6):578-86.
22. Debol SM, Herron MJ, Nelson RD. Anti‐inflammatory action of dapsone: inhibition of neutrophil adherence is associated with inhibition of chemoattractant‐induced signal transduction. Journal of leukocyte biology. 1997;62(6):827-36.
23. Bonney RJ, Humes JL. Physiological and pharmacological regulation of prostaglandin and leukotriene production by macrophages. Journal of leukocyte biology. 1984;35(1):1-10.
24. Wozel G, Barth J. Current aspects of modes of action of dapsone. International journal of dermatology. 1988;27(8):547-52.
25. Kettle AJ, Winterbourn CC. Mechanism of inhibition of myeloperoxidase by anti-inflammatory drugs. Biochemical pharmacology. 1991;41(10):1485-92.
26. Hajrezaie M, Salehen N, Karimian H, Zahedifard M, Shams K, Al Batran R, et al. Biochanin a gastroprotective effects in ethanol-induced gastric mucosal ulceration in rats. PloS one. 2015;10(3):e0121529.
27. Warzecha Z, Dembinski A, Brzozowski T, Ceranowicz P, Dembinski M, Stachura J, et al. Histamine in stress ulcer prophylaxis in rats. Journal of physiology and pharmacology. 2001;52(3).
28. Bhattacharya S, Chaudhuri SR, Chattopadhyay S, Bandyopadhyay SK. Healing properties of some Indian medicinal plants against indomethacin-induced gastric ulceration of rats. Journal of Clinical Biochemistry and Nutrition. 2007;41(2):106-14.
29. Dehpour AR, Mani AR, Amanlou M, Nahavandi A, Amanpour S, Bahadori M. Naloxone is protective against indomethacin-induced gastric damage in cholestatic rats. Journal of gastroenterology. 1999;34(2):178-81.
30. Hernández-Muñoz R, Montiel-Ruíz C, Vázquez-Martínez O. Gastric mucosal cell proliferation in ethanol-induced chronic mucosal injury is related to oxidative stress and lipid peroxidation in rats. Laboratory Investigation. 2000;80(8):1161.
31. Lee M-Y, Shin I-S, Jeon W-Y, Seo C-S, Ha H, Huh J-I, et al. Protective effect of Bojungikki-tang, a traditional herbal formula, against alcohol-induced gastric injury in rats. Journal of Ethnopharmacology. 2012;142(2):346-53.
32. Arab HH, Salama SA, Omar HA, Arafa E-SA, Maghrabi IA. Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions. PloS one. 2015;10(3).
33. Verma S, Kumar VL. Attenuation of gastric mucosal damage by artesunate in rat: modulation of oxidative stress and NFκB mediated signaling. Chemico-biological interactions. 2016;257:46-53.
34. Al Asmari A, Al Shahrani H, Al Masri N, Al Faraidi A, Elfaki I, Arshaduddin M. Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation. Toxicology reports. 2016;3:105-13.
35. Rozza AL, de Faria FM, Brito ARS, Pellizzon CH. The gastroprotective effect of menthol: involvement of anti-apoptotic, antioxidant and anti-inflammatory activities. PloS one. 2014;9(1):e86686.
36. Zheng Y-F, Xie J-H, Xu Y-F, Liang Y-Z, Mo Z-Z, Jiang W-W, et al. Gastroprotective effect and mechanism of patchouli alcohol against ethanol, indomethacin and stress-induced ulcer in rats. Chemico-Biological Interactions. 2014;222:27-36.
37. Watanabe T, Higuchi K, Tominaga K, Fujiwara Y, Arakawa T. Acid regulates inflammatory response in a rat model of induction of gastric ulcer recurrence by interleukin 1β. Gut. 2001;48(6):774-81.
38. Li W, Huang H, Niu X, Fan T, Mu Q, Li H. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice. Toxicology and applied pharmacology. 2013;272(1):21-9.
39. Arab HH, Salama SA, Omar HA, Arafa E-SA, Maghrabi IA. Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions. PloS one. 2015;10(3):e0122417.
40. Yasukawa K, Kasazaki K, Hyodo F, Utsumi H. Non-invasive analysis of reactive oxygen species generated in rats with water immersion restraint-induced gastric lesions using in vivo electron spin resonance spectroscopy. Free radical research. 2004;38(2):147-55.
41. Hamaguchi M, Watanabe T, Higuchi K, Tominaga K, Fujiwara Y, Arakawa T. Mechanisms and roles of neutrophil infiltration in stress-induced gastric injury in rats. Digestive diseases and sciences. 2001;46(12):2708-15.
42. Chauhan I, Agrawal S, Goel RK. Status of inflammatory markers and growth factor in gastric ulcer protective effects of Punica granatum L. peel extract in rat. National Journal of Physiology, Pharmacy and Pharmacology. 2018;8(1):12-7.
43. Jia Y-T, Ma B, Wei W, Xu Y, Wang Y, Tang H-T, et al. Sustained activation of nuclear factor-κB by reactive oxygen species is involved in the pathogenesis of stress-induced gastric damage in rats. Critical care medicine. 2007;35(6):1582-91.
44. Rashidian A, Rashki A, Abdollahi A, Haddadi N-S, Chamanara M, Mumtaz F, et al. Dapsone reduced acetic acid-induced inflammatory response in rat colon tissue through inhibition of NF-kB signaling pathway. Immunopharmacology and Immunotoxicology. 2019;41(6):607-13.
45. Bozeman PM, Learn DB, Thomas EL. Inhibition of the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase by dapsone. Biochemical pharmacology. 1992;44(3):553-63.
46. Martin GR, Wallace JL. Gastrointestinal inflammation: a central component of mucosal defense and repair. Experimental Biology and Medicine. 2006;231(2):130-7.
47. Takahashi S, Fujita T, Yamamoto A. Role of nuclear factor-κB in gastric ulcer healing in rats. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2001;280(6):G1296-G304.
48. Yadav SK, Adhikary B, Chand S, Maity B, Bandyopadhyay SK, Chattopadhyay S. Molecular mechanism of indomethacin-induced gastropathy. Free radical biology and medicine. 2012;52(7):1175-87.
49. Katary M, Salahuddin A. Gastroprotective effect of vanillin on indomethacin-induced gastric ulcer in rats: protective pathways and anti-Secretory mechanism. Clin Exp Pharmacol. 2017;7(2):2161-1459.1000232.
50. Kataoka H, Horie Y, Koyama R, Nakatsugi S, Furukawa M. Interaction between NSAIDs and steroid in rat stomach. Digestive diseases and sciences. 2000;45(7):1366-75.
51. Matsui H, Shimokawa O, Kaneko T, Nagano Y, Rai K, Hyodo I. The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine. Journal of clinical biochemistry and nutrition. 2011;48(2):107-11.
2. Susser M, Stein Z. Civilisation and peptic ulcer. The Lancet. 1962;279(7221):116-9.
3. Huang J-Q, Sridhar S, Hunt RH. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis. The Lancet. 2002;359(9300):14-22.
4. Piper JM, Ray WA, Daugherty JR, Griffin MR. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Annals of internal medicine. 1991;114(9):735-40.
5. Chou SP. An examination of the alcohol consumption and peptic ulcer association—Results of a national survey. Alcoholism: Clinical and Experimental Research. 1994;18(1):149-53.
6. Ramakrishnan K, Salinas RC. Peptic ulcer disease. American family physician. 2007;76(7).
7. Collier DS, Pain J. Non-steroidal anti-inflammatory drugs and peptic ulcer perforation. Gut. 1985;26(4):359-63.
8. Warzecha Z, Ceranowicz P, Dembinski M, Cieszkowski J, Ginter G, Ptak-Belowska A, et al. Involvement of cyclooxygenase-1 and cyclooxygenase-2 activity in the therapeutic effect of ghrelin in the course of ethanol-induced gastric ulcers in rats. J Physiol Pharmacol. 2014;65(1):95-106.
9. Warzecha Z, Dembiński A, Ceranowicz P, Konturek SJ, Tomaszewska R, Stachura J, et al. Inhibition of cyclooxygenase-2 reduces the protective effect of hepatocyte growth factor in experimental pancreatitis. European journal of pharmacology. 2004;486(1):107-19.
10. Brzozowski T, Konturek P, Konturek S, Pajdo R, Schuppan D, Drozdowicz D, et al. Involvement of cyclooxygenase (COX)-2 products in acceleration of ulcer healing by gastrin and hepatocyte growth factor. Journal of Physiology and Pharmacology. 2000;51(4, 1).
11. Sørbye H, Svanes K. The role of blood flow in gastric mucosal defence, damage and healing. Digestive Diseases. 1994;12(5):305-17.
12. Hollander D, Tarnawski A, Krause WJ, Gergely H. Protective effect of sucralfate against alcohol-induced gastric mucosal injury in the rat: macroscopic, histologic, ultrastructural, and functional time sequence analysis. Gastroenterology. 1985;88(1):366-74.
13. Oates PJ, Hakkinen JP. Studies on the mechanism of ethanol-induced gastric damage in rats. Gastroenterology. 1988;94(1):10-21.
14. Plummer MP, Blaser AR, Deane AM. Stress ulceration: prevalence, pathology and association with adverse outcomes. Critical Care. 2014;18(2):213.
15. Lanas A, Chan FK. Peptic ulcer disease. The Lancet. 2017;390(10094):613-24.
16. Mahmood A, Al-Bayaty F, Salmah I, AB NS, Harita H. Enhancement of gastric ulcer by Areca catechu nut in ethanol-induced gastric mucosal injuries in rats. Journal of Medicinal Plants Research. 2011;5(12):2462-9.
17. Suzuki H, Nishizawa T, Tsugawa H, Mogami S, Hibi T. Roles of oxidative stress in stomach disorders. Journal of clinical biochemistry and nutrition. 2011:1112080129-.
18. Soll AH. Pathogenesis of peptic ulcer and implications for therapy. New England Journal of Medicine. 1990;322(13):909-16.
19. Farrar J, Hotez PJ, Junghanss T, Kang G, Lalloo D, White NJ. Manson's Tropical Diseases E-Book: Expert Consult-Online and Print: Elsevier Health Sciences; 2013.
20. Wozel G, Blasum C. Dapsone in dermatology and beyond. Archives of dermatological research. 2014;306(2):103-24.
21. Lewis AJ, Gemmell DK, Stimson WH. The anti-inflammatory profile of dapsone in animal models of inflammation. Agents and actions. 1978;8(6):578-86.
22. Debol SM, Herron MJ, Nelson RD. Anti‐inflammatory action of dapsone: inhibition of neutrophil adherence is associated with inhibition of chemoattractant‐induced signal transduction. Journal of leukocyte biology. 1997;62(6):827-36.
23. Bonney RJ, Humes JL. Physiological and pharmacological regulation of prostaglandin and leukotriene production by macrophages. Journal of leukocyte biology. 1984;35(1):1-10.
24. Wozel G, Barth J. Current aspects of modes of action of dapsone. International journal of dermatology. 1988;27(8):547-52.
25. Kettle AJ, Winterbourn CC. Mechanism of inhibition of myeloperoxidase by anti-inflammatory drugs. Biochemical pharmacology. 1991;41(10):1485-92.
26. Hajrezaie M, Salehen N, Karimian H, Zahedifard M, Shams K, Al Batran R, et al. Biochanin a gastroprotective effects in ethanol-induced gastric mucosal ulceration in rats. PloS one. 2015;10(3):e0121529.
27. Warzecha Z, Dembinski A, Brzozowski T, Ceranowicz P, Dembinski M, Stachura J, et al. Histamine in stress ulcer prophylaxis in rats. Journal of physiology and pharmacology. 2001;52(3).
28. Bhattacharya S, Chaudhuri SR, Chattopadhyay S, Bandyopadhyay SK. Healing properties of some Indian medicinal plants against indomethacin-induced gastric ulceration of rats. Journal of Clinical Biochemistry and Nutrition. 2007;41(2):106-14.
29. Dehpour AR, Mani AR, Amanlou M, Nahavandi A, Amanpour S, Bahadori M. Naloxone is protective against indomethacin-induced gastric damage in cholestatic rats. Journal of gastroenterology. 1999;34(2):178-81.
30. Hernández-Muñoz R, Montiel-Ruíz C, Vázquez-Martínez O. Gastric mucosal cell proliferation in ethanol-induced chronic mucosal injury is related to oxidative stress and lipid peroxidation in rats. Laboratory Investigation. 2000;80(8):1161.
31. Lee M-Y, Shin I-S, Jeon W-Y, Seo C-S, Ha H, Huh J-I, et al. Protective effect of Bojungikki-tang, a traditional herbal formula, against alcohol-induced gastric injury in rats. Journal of Ethnopharmacology. 2012;142(2):346-53.
32. Arab HH, Salama SA, Omar HA, Arafa E-SA, Maghrabi IA. Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions. PloS one. 2015;10(3).
33. Verma S, Kumar VL. Attenuation of gastric mucosal damage by artesunate in rat: modulation of oxidative stress and NFκB mediated signaling. Chemico-biological interactions. 2016;257:46-53.
34. Al Asmari A, Al Shahrani H, Al Masri N, Al Faraidi A, Elfaki I, Arshaduddin M. Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation. Toxicology reports. 2016;3:105-13.
35. Rozza AL, de Faria FM, Brito ARS, Pellizzon CH. The gastroprotective effect of menthol: involvement of anti-apoptotic, antioxidant and anti-inflammatory activities. PloS one. 2014;9(1):e86686.
36. Zheng Y-F, Xie J-H, Xu Y-F, Liang Y-Z, Mo Z-Z, Jiang W-W, et al. Gastroprotective effect and mechanism of patchouli alcohol against ethanol, indomethacin and stress-induced ulcer in rats. Chemico-Biological Interactions. 2014;222:27-36.
37. Watanabe T, Higuchi K, Tominaga K, Fujiwara Y, Arakawa T. Acid regulates inflammatory response in a rat model of induction of gastric ulcer recurrence by interleukin 1β. Gut. 2001;48(6):774-81.
38. Li W, Huang H, Niu X, Fan T, Mu Q, Li H. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice. Toxicology and applied pharmacology. 2013;272(1):21-9.
39. Arab HH, Salama SA, Omar HA, Arafa E-SA, Maghrabi IA. Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions. PloS one. 2015;10(3):e0122417.
40. Yasukawa K, Kasazaki K, Hyodo F, Utsumi H. Non-invasive analysis of reactive oxygen species generated in rats with water immersion restraint-induced gastric lesions using in vivo electron spin resonance spectroscopy. Free radical research. 2004;38(2):147-55.
41. Hamaguchi M, Watanabe T, Higuchi K, Tominaga K, Fujiwara Y, Arakawa T. Mechanisms and roles of neutrophil infiltration in stress-induced gastric injury in rats. Digestive diseases and sciences. 2001;46(12):2708-15.
42. Chauhan I, Agrawal S, Goel RK. Status of inflammatory markers and growth factor in gastric ulcer protective effects of Punica granatum L. peel extract in rat. National Journal of Physiology, Pharmacy and Pharmacology. 2018;8(1):12-7.
43. Jia Y-T, Ma B, Wei W, Xu Y, Wang Y, Tang H-T, et al. Sustained activation of nuclear factor-κB by reactive oxygen species is involved in the pathogenesis of stress-induced gastric damage in rats. Critical care medicine. 2007;35(6):1582-91.
44. Rashidian A, Rashki A, Abdollahi A, Haddadi N-S, Chamanara M, Mumtaz F, et al. Dapsone reduced acetic acid-induced inflammatory response in rat colon tissue through inhibition of NF-kB signaling pathway. Immunopharmacology and Immunotoxicology. 2019;41(6):607-13.
45. Bozeman PM, Learn DB, Thomas EL. Inhibition of the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase by dapsone. Biochemical pharmacology. 1992;44(3):553-63.
46. Martin GR, Wallace JL. Gastrointestinal inflammation: a central component of mucosal defense and repair. Experimental Biology and Medicine. 2006;231(2):130-7.
47. Takahashi S, Fujita T, Yamamoto A. Role of nuclear factor-κB in gastric ulcer healing in rats. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2001;280(6):G1296-G304.
48. Yadav SK, Adhikary B, Chand S, Maity B, Bandyopadhyay SK, Chattopadhyay S. Molecular mechanism of indomethacin-induced gastropathy. Free radical biology and medicine. 2012;52(7):1175-87.
49. Katary M, Salahuddin A. Gastroprotective effect of vanillin on indomethacin-induced gastric ulcer in rats: protective pathways and anti-Secretory mechanism. Clin Exp Pharmacol. 2017;7(2):2161-1459.1000232.
50. Kataoka H, Horie Y, Koyama R, Nakatsugi S, Furukawa M. Interaction between NSAIDs and steroid in rat stomach. Digestive diseases and sciences. 2000;45(7):1366-75.
51. Matsui H, Shimokawa O, Kaneko T, Nagano Y, Rai K, Hyodo I. The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine. Journal of clinical biochemistry and nutrition. 2011;48(2):107-11.
| Files | ||
| Issue | Vol 59, No 6 (2021) | |
| Section | Articles | |
| DOI | https://doi.org/10.18502/acta.v59i6.6895 | |
| Keywords | ||
| Inflammation Dapsone Ethanol Stress Indomethacin Gastric erosion | ||
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How to Cite
1.
Sheibani M, Nezamoleslami S, Rahimi N, Abbasi A, Dehpour AR. The protective effect of dapsone against ethanol-; stress-; and indomethacin-induced gastric erosion in rats. Acta Med Iran. 2021;59(6):364-375.
