Skip to main content

The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage

Abstract

The aim of this study was to assess the possible protective effects of Nigella sativa (NS) and its constituent, thymoquinone (TQ) on ethanol-induced gastric mucosal damage in an experimental model. Forty male rats aged four months were divided into four groups (each group containing ten animals); the control group received physiologic saline (10 ml kg−1) and the ethanol group had taken 1 ml (per rat) absolute alcohol by gavage. The third and fourth groups also received NS (500 mg kg−1) and TQ (10 mg kg−1) by gavage 1 h before alcohol administration, respectively. Both drugs (NS and TQ) could protect the gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index values. Gastric damage was confirmed histomorphometrically by significant increases in the number of mast cells (MC) and gastric erosions in ethanol treated rats. The NS treatment significantly decreased the number of MC and reduced the area of gastric erosions. Likewise, TQ treatment was also able to reduce the number of MC and the gravity of gastric mucosal lesions, but to lesser extent compared to NS. Gastric tissue histamine levels and myeloperoxidase activities were found to be increased in ethanol treated rats, and NS or TQ treatment reversed these increases. Results obtained from this study suggest that both drugs, particularly NS could partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects could be due to their antiperoxidative, antioxidant and antihistaminic effects.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

References

  1. Al-Ghamdi MS (2001) The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol 76:45–48

    Article  PubMed  CAS  Google Scholar 

  2. Badary OA, Al-Shabanah OA, Nagi MN, Al-Rikabi AC, Elmazar MM (1999) Inhibition of benzo(a)pyrene-induced forestomach carcinogenesis in mice by thymoquinone. Eur J Cancer Prev 8:435–440

    PubMed  Article  CAS  Google Scholar 

  3. Bast A, Haenen GRMM, Doelman CJA (1991) Oxidant and antioxidant: state of the art. Am J Med 91:2–13

    Article  Google Scholar 

  4. Bradley PP, Friebal DA, Christensen RD (1982) Measurements of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78:206–209

    Article  PubMed  CAS  Google Scholar 

  5. Burtis M, Bucar F (2000) Antioxidant activity of Nigella sativa essential oil. Phytother Res 14:323–328

    Article  PubMed  Google Scholar 

  6. Capasso R, Pinto L, Vuotto ML, Di Carlo G (2000) Preventive effect of eugenol on PAF and ethanol-induced gastric mucosal damage. Fitoterapia 71:131–137

    Article  Google Scholar 

  7. Chakravarty N (1993) Inhibition of histamine release from mast cells by nigellone. Ann Allergy 70:237–242

    PubMed  CAS  Google Scholar 

  8. Cho CH, Pfeiffer CJ, Misra HP (1991) Ulcerogenic mechanism of ethanol and the activation of sulphanilyl on the rat stomach in vivo. J Pharm Pharmacol 43:495–498

    PubMed  CAS  Google Scholar 

  9. Daba MH, Abdel Rahman MS (1998) Hepatoprotective activity of thymoquinone in isolated rat hepatocytes. Toxicol Lett 16:23–29

    Article  Google Scholar 

  10. El-Dakhakhny M, Barakat M, El-Halim MA, Aly SM (2000) Effects of Nigella sativa oil on gastric secretion and ethanol induced ulcer in rats. J Ethnopharmacol 72:299–304

    Article  PubMed  CAS  Google Scholar 

  11. El-Kadi A, Kandil O (1987) The black seed (Nigella sativa) and immunity: its effect on human T cell subset. Fed Proc 46:1222

    Google Scholar 

  12. El-Kadi A, Kandil O, Tabuni AM (1987) Nigella cell mediated immunity. Arch AIDS Res 1:232–233

    Google Scholar 

  13. El-Tahir KE, Ashour MM, Al-Harbi MM (1993a) The cardiovascular actions of the volatile oil of the black seed (Nigella sativa) in rats: elucidation of the mechanism(s) of action. Gen Pharmacol 24:1123–1131

    PubMed  CAS  Google Scholar 

  14. El-Tahir KE, Ashour MM, Al-Harbi MM (1993b) The respiratory effects of the volatile oil of the black seed (Nigella sativa) in guinea-pigs: elucidation of the mechanism(s) of action. Gen Pharmacol 24:1115–1122

    PubMed  CAS  Google Scholar 

  15. Fararh KM, Atoji Y, Shimizu Y, Takewaki T (2002) Isulinotropic properties of Nigella sativa oil in Streptozotocin plus Nicotinamide diabetic hamster. Res Vet Sci 73:279–282

    Article  PubMed  CAS  Google Scholar 

  16. Hanafy MSM, Hatem ME (1991) Studies on the antimicrobial activity of Nigella sativa seed (black cumin). J Ethnopharmacol 34:275–278

    Article  PubMed  CAS  Google Scholar 

  17. Hernández-Muñoz R, Montiel-Ruíz C, Vázquez-Martínez O (2000) Gastric mucosal cell proliferation in ethanol-induced chronic mucosal injury is related to oxidative stress and lipid peroxidation in rats. Lab Invest 80:1161–1169

    PubMed  Google Scholar 

  18. Hirokawa M, Miura S, Yoshida H, et al (1998) Oxidative stress and mitochondrial damage precedes gastric mucosal cell that induced by ethanol administration. Alcohol Clin Exp Res 22:111–114

    PubMed  Article  Google Scholar 

  19. Houghton PJ, Zarka R, Heras B, Hoult RS (1995) Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leucocytes and membrane lipid peroxidation. Planta Med 61:33–36

    PubMed  Article  CAS  Google Scholar 

  20. Kahraman A, Erkasap N, Köken T, Serteser M, Aktepe F, Erkasap S (2003) The antioxidative and antihistaminic properties of quercetin in ethanol-induced gastric lesions. Toxicology 183:133–142

    Article  PubMed  CAS  Google Scholar 

  21. Kanter M, Meral I, Yener Z, Ozbek H, Demir H (2003) Partial regeneration/proliferation of the β-cells in the islets of Langerhans by Nigella sativa L. in streptozocin-induced diabetic rats. Tohoku J Exp Med 20:213–219

    Article  Google Scholar 

  22. Kanter M, Coskun O, Korkmaz A, Oter S (2004) Effects of Nigella sativa on oxidative stress and β-cell damage in streptozocin-induced diabetic rats. Anat Rec 279:685–691

    Article  CAS  Google Scholar 

  23. Kruk I, Michalska T, Lichszteld K, Klanda A, Aboul-Enein HY (2000) The effect of thymol and its derivatives on reactions generating reactive oxygen species. Chemosphere 41:1059–1064

    Article  PubMed  CAS  Google Scholar 

  24. La Casa C, Villegas I, Alarcon de La Lastra C, Motilva V, Martin Calero MJ (2000) Evidence for protective and antioxidant properties of rutin, natural flavone, against ethanol induced gastric lesions. J Ethnopharmocol 71:45–53

    Article  CAS  Google Scholar 

  25. Lorenz W, Barth H, Kusche J, et al (1971) Histamine in the pig: determination, distribution, release and pharmacological actions. Eur J Pharmacol 14:155–175

    Article  PubMed  CAS  Google Scholar 

  26. Lutnicki K, Wrobel J, Ledwozyw A, Trebas-Pietras E (1992) The effect of calcium ions on the intensity of peroxidation processes and the severity of ethanol-induced injury to the rat’s gastric mucosa. Arch Vet Pol 32:125–132

    PubMed  CAS  Google Scholar 

  27. Mizui T, Sato H, Hirose F, Doteuchi M (1987) Effect of antiperoxidative drugs on damage induced by ethanol in rats. Life Sci 41:755–763

    Article  PubMed  CAS  Google Scholar 

  28. Nagi MN, Mansour MA (2000) Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection. Pharmacol Res 41:283–289

    Article  PubMed  CAS  Google Scholar 

  29. Nagi MN, Alam K, Badary OA, Al-Shabanah OA, Al-Sawaf HA, Al-Bekairi AM (1999) Thymoquinone protects against carbon tetrachloride hepatotoxicity in mice via an antioxidant mechanism. Biochem Mol Biol Int 47:53–159

    Google Scholar 

  30. Natale G, Lazzeri G, Blandizzi C, et al (2001) Seriate histomorphometry of whole rat stomach: an accurate and reliable method for quantitative analysis of mucosal damage. Toxicol Appl Pharmacol 174:17–26

    Article  PubMed  CAS  Google Scholar 

  31. Ogle CW, Cho CH (1989) The protective mechanism of FPL55712 against stress-induced gastric ulceration in rats. Agents Actions 26:350–354

    Article  PubMed  CAS  Google Scholar 

  32. Saleh S, El-Denshary EMS, Mahran LG, Salah N (2000) Anti-inflammatory and antioxidant effect of Nigella sativa oil in sensitized animals. 25th International Conference on Science and Technology, New Delhi

  33. Salim SA (1990) Removing oxygen-derived free radicals stimulates healing of ethanol induced erosive gastritis in rat. Digestion 47:24–28

    PubMed  CAS  Article  Google Scholar 

  34. Sen T, Abdul Salam CA, Siddhartha P, Suchandra S, Nag Chaudhuri AK (2000) Effect of dothiepin on gastric ulceration mediated by lipid derived eicosanoids. Life Sci 66:325–330

    Article  Google Scholar 

  35. Stadtman ER, Berlett BS (1997) Free-radical-mediated modification of proteins. In: Wallace KB (ed) Free radical toxicology. Taylor & Francis, Bristol, pp 71–87

  36. Szabo S, Trier JS, Frankel PW (1981) Sulfhydryl compounds may mediate gastric cytoprotection. Science 214:200–202

    PubMed  Article  CAS  Google Scholar 

  37. Thomson A, Hemphill D, Jeejeebhoy KN (1998) Oxidative stress and antioxidant in intestinal diseases. Dig Dis 16:152–158

    Article  PubMed  CAS  Google Scholar 

  38. Toyokuni S (1999) Reactive oxygen species induced molecular damage and its application in pathology. Pathol Int 49:91–102

    Article  PubMed  CAS  Google Scholar 

  39. Tsuji S, Kawano S, Sato N, Kamada T (1990) Mucosal blood flow stasis and hypoxemia as the pathogenesis of acute gastric mucosal injury: role of endogenous leukotrienes and prostaglandins. J Clin Gastroenterol 12:85–91

    PubMed  Article  Google Scholar 

  40. Turkdogan MK, Agaoglu Z, Yener Z, Sekeroglu R, Akkan HA, Avci ME (2001) The role of antioxidant vitamins (C and E), selenium and Nigella sativa in the prevention of liver fibrosis and cirrhosis in rabbits: new hopes. Dtsch Tierarztl Wochenschr 108:71–73

    PubMed  CAS  Google Scholar 

  41. Yoshikawa T, Ueda S, Naito Y, et al (1989) Role of oxygen-derived free radicals in gastric mucosal injury induced by ischaemia-reperfusion in rats. Free Radic Res Commun 7:285–291

    PubMed  Article  CAS  Google Scholar 

  42. Yoshikawa T, Naito Y, Tanigawa T, et al (1991) Effect of zinc-carnosine chelate compound (Z-103), a novel antioxidant, on acute gastric mucosal injury induced by ischaemia-reperfusion in rats. Free Radic Res Commun 14:289–296

    PubMed  Article  CAS  Google Scholar 

  43. Zaoui A, Cherrah Y, Lacaille-Dubois MA, Settaf A, Amarouch H, Hassar M (2000) Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rat. Therapie 55:379–382

    PubMed  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Mehmet Kanter.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kanter, M., Coskun, O. & Uysal, H. The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage. Arch Toxicol 80, 217–224 (2006). https://doi.org/10.1007/s00204-005-0037-1

Download citation

Keywords

  • Nigella sativa
  • Thymoquinone
  • Ulcer
  • Antioxidant
  • Antihistaminic
  • Rat