Protective effects of vitamin B6 alone and in combination with L-cysteine and NaHS on ethanol and indomethacin-induced gastric lesions in mice

Document Type: Original Article

Authors

1 Research center for Infectious Diseases of Digestive System, Physiology Research Center, and Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Physiology Research Center, and Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Objective(s):  This study was undertaken to investigate the protective effects of vitamin B6, cofactor for cystathionine-γ lyase and cystathionine-β synthase (producers of H2S), alone and in combination with L-cysteine, H2S precursor, on indomethacin-, and ethanol-induced gastric lesions in male NMRI mice.
Materials and Methods: Fasted male NMRI mice were randomly assigned into 12 groups (7 in each). The gastroprotective activity of vitamin B6 alone and in combination with L-cysteine and sodium hydrosulfate (NaHS) was evaluated against ethanol-, and indomethacin-induced gastric lesions. The animals were received vehicle, vitamin B6, L-cysteine, L-cysteine+vitamin B6, NaHS or NaHS+B6 before the induction of gastric lesions by ethanol (50%, 0.5 ml/25 g of body weight, orally) or indomethacin (40 mg/kg, orally). One and five hours after the administration of ethanol and indomethacin, respectively, the animals were sacrificed using anesthetics. The stomachs were removed, rinsed with normal saline and assessed for gastric wall mucus changes.
Results: Pretreatment with L-cysteine, sodium hydrosulfate, and vitamin B6 significantly decreased the total area of gastric lesions (P<0.01). The mucus production in L-cysteine-, sodium hydrosulfate-, and vitamin B6-treated animals were significantly higher than in control rats (P<0.05). The gastroprotective activity of L-cysteine and sodium hydrosulfate in combination with vitamin B6 were higher than when administered alone (P<0.05).    
Conclusion: The result of this survey showed that the protective activity of L-cysteine and sodium hydrosulfate enhances in the presence of vitamin B6.

Keywords


1. Guidotti TL. Hydrogen sulphide. Occup Med (Lond) 1996; 46:367-371.

2. Moore PK, Bhatia M, Moochhala S. Hydrogen sulfide: from the smell of the past to the mediator of the future? Trend Pharmacol Sci 2003; 24:609-611.

3. Fiorucci S, Antonelli E, Distrutti E, Rizzo G, Mencarelli A, Orlandi S, et al. Inhibition of hydrogen sulfide generation contributes to gastric injury caused by anti-inflammatory nonsteroidal drugs. Gastroenterology 2005; 129:1210-1224.

4. Wallace JL, Dicay M, McKnight W, Martin GR. Hydrogen sulfide enhances ulcer healing in rats. FASEB J 2007; 21:4070-4076.

5. Mard SA, Neisi N, Solgi G, Hassanpour M, Darbor M, Maleki M. Gastroprotective effect of NaHS against mucosal lesions induced by ischemia–reperfusion injury in rat. Dig Dis Sci 2012; 57:1496-1503.

6. Wallace JL. Hydrogen sulfide: a rescue molecule for mucosal defence and repair. Dig Dis Sci 2012; 57:1432-1434.

7. Fiorucci S, Orlandi S, Mencarelli A, Caliendo G, Santagada V, Distrutti E, et al. Enhanced activity of a hydrogen sulphide‐releasing derivative of mesalamine (ATB‐429) in a mouse model of colitis. Br J Pharmacol 2007; 150:996-1002.

8. Ise F, Takasuka H, Hayashi S, Takahashi K, Koyama M, Aihara E, et al. Stimulation of duodenal HCO3− secretion by hydrogen sulphide in rats: relation to prostaglandins, nitric oxide and sensory neurones. Acta Physiol 2011; 201:117-126.

9. Wallace JL, Vong L, McKnight W, Dicay M, Martin GR. Endogenous and exogenous hydrogen sulfide promotes resolution of colitis in rats. Gastro-enterology 2009; 137:569-578.

10. Goubern M, Andriamihaja M, Nübel T, Blachier F, Bouillaud F. Sulfide, the first inorganic substrate for human cells. FASEB J. 2007; 21:1699-1706.

11. Szabó C, Papapetropoulos A. Hydrogen sulphide and angiogenesis: mechanisms and applications. Br J Pharmacol 2011; 164:853-865.

12. Medeiros JVR, Bezerra VH, Gomes AS, Barbosa ALR, Lima-Júnior RCP, Soares PMG, et al. Hydrogen sulfide prevents ethanol-induced gastric damage in mice: role of ATP-sensitive potassium channels and capsaicin-sensitive primary afferent neurons. J Pharmacol Exp Ther 2009; 330:764-770.

13. Masisi K, Suidasari S, Zhang P, Okazaki Y, Yanaka N, Kato N. Comparative study on the responses of concentrations of B(6)-vitamers in several tissues of mice to the dietary level of pyridoxine. J Nutr Sci Vitaminol 2012; 58:446-451.

14. Mard SA, Askari H, Neisi N, Veisi A. Antisecretory effect of hydrogen sulfide on gastric acid secretion and the involvement of nitric oxide. BioMed Res Int. 2014;2014.

15. Plants A, Karaj I. Effects of saffron and its active constituents, crocin and safranal, on prevention of indomethacin induced gastric ulcers in diabetic and nondiabetic rats. J Med Plants 2009; 8:30-38.

16. Perera LM, Ruedas D, Gómez BC. Gastric antiulcer effect of Rhizophora mangle L. J Ethnopharmacol 2001; 77:1-3.

17. Nalli AD. Regulation of gastroin testinal smooth

muscle function: Virginia Commonwealth University Richmond, Virginia; 2013.

18. Hellmann H, Mooney S. Vitamin B6: a molecule for human health? Molecules 2010; 15:442-459.

19. Pahlavanzadeh F, Bidadkosh A, Derakhshanfar A, Rastegar AM, Rushanzamir M. Antioxidant protecting effects of vitamin B6 at reducing hemodynamic toxicity of gentamicin in rat model of nephrotoxicity. Comp Clin Pathol 2013; 22:637-643.

20. Perry T, Holloway HW, Weerasuriya A, Mouton PR, Duffy K, Mattison JA, et al. Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy. Exp Neurol 2007; 203:293-301.

21. Yanaka N, Koyama T, Komatsu S, Nakamura E, Kanda M, Kato N. Vitamin B6 suppresses NF-kB activation in LPS-stimulated mouse macrophages. Int J Mol Med 2005; 16:1071-1076.

22. Komatsu S, Watanabe H, Oka T, Tsuge H, Kat N. Dietary vitamin B6 suppresses colon tumorigenesis, 8-hydroxyguanosine, 4-hydroxynonenal, and inducible nitric oxide synthase protein in azoxymethane-treated mice. J Nutr Sci Vitaminol 2002; 48:65-68.

23. Musumba C, Pritchard D, Pirmohamed M. Review article: cellular and molecular mechanisms of NSAID‐induced peptic ulcers. Aliment Pharmacol Ther 2009; 30:517-531.

24. Jones MK, Wang H, Peskar BM, Levin E, Itani RM, Sarfeh IJ, et al. Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing. Nat Med 1999; 5:1418-1423.

25. Inas ZA, Hala AK, Gehan HH. Gastroprotective effect of Cordia myxa L. fruit extract against indomethacin-induced gastric ulceration in rats. Life Sci J 2011; 8:433-445.

26. Yusuf M, Kwong Huat BT, Hsu A, Whiteman M, Bhatia M, Moore PK. Streptozotocin-induced diabetes in the rat is associated with enhanced tissue hydrogen sulfide biosynthesis. Biochem Biophys Res Commun 2005; 333:1146-1152.

27. Bhatia M, Wong FL, Fu D, Lau HY, Moochhala SM, Moore PK. Role of hydrogen sulfide in acute pancreatitis and associated lung injury. FASEB J 2005; 19:623-625.

28. Szabo S, Trier J, Brown A, Schnoor J. Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat. Gastroenterology 1985; 88:228-236.

29. Peskar B, Lange K, Hoppe U, Peskar B. Ethanol stimulates formation of leukotriene C4 in rat gastric mucosa. Prostaglandins 1986; 31:283-293.

30. Guslandi M. Effects of ethanol on the gastric mucosa. Dig Dis 1987; 5:21-32.