Journal of IMAB - Annual Proceeding (Scientific Papers)
Publisher: Peytchinski, Gospodin Iliev
ISSN: 1312 773X (Online)
Issue: 2015, vol. 21, issue 2
Subject Area: Medicine - Pathophysiology
Pages: 779-783
DOI: 10.5272/jimab.2015212.779
Published online: 21 May 2015

J of IMAB 2015 Apr-Jun;21(2):779-783
Minka Hristova1Corresponding Autor, Ganka Bekyarova1, Maria Tzaneva2.
1) Divison of Pathophysiology, Faculty of Medicine, Medical University of Varna, Bulgaria
2) Department of Clinical and Preclinical Sciences, Faculty of Pharmacy , Medical University of Varna, Bulgaria.

Melatonin is indoleamine hormone derived from L-tryptophan. Due to its lipophilic nature, it is accessible to every cell. Melatonin has immunomodulatory and antioxidant activities thus protecting tissue injury. Heat shock proteins such as HSP32 known as heme oxygenase-1 (HO-1) possesses antioxidant, anti-inflammatory, and vasodilatory properties and plays an important role in the protecting of tissues from several stresses. The aim of study is to investigate the expression of HO-1 in gastric mucosa and its connection with oxidative stress and melatonin mediated protection after thermal injury. On rats back, under anesthesia, third degree burn was applied involving 30% of total body surface area (TBSA). Melatonin (10 mg per kg body mass) was injected i.p. immediately and 12 hours after thermal skin injury. We used tissue malondialdehyde (MDA), lipid peroxidation product, as a marker of oxidative stress. Gastric mucosa histopathology were observed on light microscopy and light immunohistochemistry investigating the HO-1 too. Results: The levels of MDA in gastric mucosa were elevated (p< 0.05). The HO-1 expression was significantly increased in rats with trauma. Melatonin inhibited elevation in lipid peroxidation product and augmented the increase in expression of HO-1 in the gastric mucosa. In conclusion, our data suggest that HO-1 induction following burn injury is an adaptive response protecting gastric mucosal against further oxidative damage.  Melatonin increased the antioxidant capacity and restricted burn-induced oxidative damage in gastric mucosa and thus could be used therapeutically in organ protection.

Key words: melatonin, heme-oxygenase 1, oxidative stress, gastric mucosa, thermal injury,

- Download FULL TEXT /PDF 1280 KB/
Please cite this article in PubMed Style or AMA (American Medical Association) Style:

Correspondence to: Dr. Minka Hristova, Divison of Pathophysiology, Medical University-Varna; 55 Marin Drinov Str., 9002 Varna, Bulgaria; E-mail:

1. Pruitt BA Jr, Goodwin CW Jr. Stress ulcer disease in the burned patient. J World Surg. 1981 Mar;5(2):209–222. [CrossRef]
2. Cakir B, Cevik H, Contuk G, Ercan F, Ekşioğlu-Demiralp E, Yeğen BC. Leptin ameliorates burn-induced multiple organ damage and modulates postburn immune response in rats. Regul Pept. 2005 Feb 15;125(1-3):135-44. [PubMed] [CrossRef]
3. Brzozowski T, Konturek PC, Drozdowicz D, Konturek SJ, Zayachivska O, Pajdo R, et al. Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways. World J Gastroenterol. 2005 Nov 7;11(41):6450-8. [PubMed]
4. Magierowski M, Jasnos K, Sliwowski Z, Surmiak M, Krzysiek-Maczka G, Ptak-Belowska A, et al. Exogenous asymmetric dimethylarginine (ADMA) in pathogenesis of ischemia-reperfusion-induced gastric lesions: interaction with protective nitric oxide (NO) and calcitonin gene-related peptide (CGRP). Int J Mol Sci. 2014 Mar 20;15(3):4946-64. [CrossRef] [PMC].     
5. Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev. 2006 Apr;86(2):583-650. [PubMed] [CrossRef]
6. Morse D, Choi AM. Heme oxygenase-1: the "emerging molecule" has arrived. Am J Respir Cell Mol Biol. 2002 Jul;27(1):8-16. [PubMed] [CrossRef]
7. Konturek PC, Celinski K, Slomka M, Cichoz-Lach H, Burnat G, Naegel A, et al. Melatonin and its precursor L-tryptophan prevent acute gastric mucosal damage induced by aspirin in humans. J Physiol Pharmacol. 2008 Aug;59 Suppl 2:67-75. [PubMed]
8. Bandyopadhyay D, Ghosh G, Bandyopadhyay A, Reiter RJ. Melatonin protects against piroxicam-induced gastric ulceration. J Pineal Res. 2004 Apr;36(3):195-203. [PubMed] [CrossRef]
9. Bandyopadhyay D, Bandyopadhyay A, Das PK, Reiter RJ. Melatonin protects against gastric ulceration and increases the efficacy of raniti] dine and omeprazole in reducing gastric damage. J Pineal Res. 2002 Aug;33(1):1-7. [PubMed] [CrossRef]
10. Kwon KJ, Kim JN, Kim MK, Lee J, Ignarro LJ, Kim HJ, et al. Melatonin synergistically increases resveratrol-induced heme oxygenase-1 expression through the inhibition of ubiquitin-dependent proteasome pathway: a possible role in neuroprotection. J Pineal Res. 2011 Mar;50(2):110-23. [PubMed] [CrossRef]
11. Porter NA, Nixon JR. Isaac R. Cyclic peroxidase and thiobarbituric assay. Biochim Biophys Acta. 1976 Sep 27;441(3):596-599. [PubMed]
12. Sener G, Sehirli AO, Satiroğlu H, Keyer-Uysal M, Yeğen BC. Melatonin improves oxidative organ damage in a rat model of thermal injury. Burns. 2002 Aug;28(5):419-25. [PubMed] [CrossRef]
13. Gurbuz V, Corak A, Yegen BC, Kurtel H, Alican I. Oxidative organ damage in a rat model of thermal injury: the effect of cyclosporin A. Burns. 1997 Feb;23(1):37–42. [PubMed] [CrossRef]
14. Hatherill JR, Till GO, Bruner LH, Ward PA. Thermal injury, intravascular hemolysis, and toxic oxygen products. J Clin Invest. 1986 Sep;78(3):629-36. [PubMed] [CrossRef]
15. Pereira CT, Jeschke MG, Herndon DN. Beta-blockade in burns. Novartis Found Symp. 2007; 280:238-48; discussion 248-51. [PubMed]
16. Bindu S, Pal C, Dey S, Goyal M, Alam A, Iqbal MS, et al. Translocation of heme oxygenase-1 to mitochondria is a novel cytoprotective mechanism against non-steroidal anti-inflammatory drug-induced mitochondrial oxidative stress, apoptosis, and gastric mucosal injury. J Biol Chem. 2011 Nov 11;286(45):39387-402. [PubMed] [CrossRef]
17. Pandi-Perumal SR, Srinivasan V, Maestroni GJ, Cardinali DP, Poeggeler B, Hardeland R. Melatonin: Nature's most versatile biological signal? FEBS J. 2006 Jul;273(13):2813-38. [PubMed] [CrossRef]
18. Konturek PC, Konturek SJ, Majka J, Zembala M, Hahn EG. Melatonin affords protection against gastric lesions induced by ischemia-reperfusion possibly due to its antioxidant and mucosal microcirculatory effects. Eur J Pharmacol. 1997 Mar 12;322(1):73-7. [PubMed] [CrossRef]
19. García JJ, Reiter RJ, Guerrero JM, Escames G, Yu BP, Oh CS, et al.. Melatonin prevents changes in microsomal membrane fluidity during induced lipid peroxidation. FEBS Lett. 1997 May 26;408(3):297-300. [PubMed] [CrossRef]
20. López-Burillo S, Tan DX, Mayo JC, Sainz RM, Manchester LC, Reiter RJ. Melatonin, xanthurenic acid, resveratrol, EGCG, vitamin C and alpha-lipoic acid differentially reduce oxidative DNA damage induced by Fenton reagents: a study of their individual and synergistic actions. J Pineal Res. 2003 May;34(4):269-77. [PubMed] [CrossRef]
21. Spanier G, Xu H, Xia N, Tobias S, Deng S, Wojnowski L, et al. Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4). J Physiol Pharmacol. 2009 Oct;60 Suppl 4:111-6. [PubMed]
22. Attuwaybi BO, Kozar RA, Moore-Olufemi SD, Sato N, Hassoun HT, Weisbrodt NW, et al. Heme oxygenase-1 induction by hemin protects against gut ischemia/reperfusion injury. J Surg Res. 2004 May 1;118(1):53-7. [PubMed] [CrossRef]
23. Gomes AS, Gadelha GG, Lima SJ, Garcia JA, Medeiros JV, Havt A, et al.. Gastroprotective effect of heme-oxygenase 1/biliverdin/CO pathway in ethanol-induced gastric damage in mice. Eur J Pharmacol. 2010 Sep 10;642(1-3):140-5. [PubMed] [CrossRef]
24. Higuchi K, Yoda Y, Amagase K, Kato S, Tokioka S, Murano M, et al. Prevention of NSAID-Induced Small Intestinal Mucosal Injury: Prophylactic Potential of Lansoprazole. J Clin Biochem Nutr. 2009 Sep;45(2):125-30. Epub 2009 Aug 28. [PubMed] [CrossRef]
25. Choi KM, Gibbons SJ, Nguyen TV, Stoltz GJ, Lurken MS, Ordog T, et al. Heme oxygenase-1 protects interstitial cells of Cajal from oxidative stress and reverses diabetic gastroparesis. Gastroenterology. 2008 Dec;135(6):2055-64, 2064.e1-2. [PubMed] [CrossRef]
26. Takagi T, Naito Y, Yoshikawa T. The expression of heme oxygenase-1 induced by lansoprazole. J Clin Biochem Nutr. 2009 Jul;45(1):9-13. [PubMed] [CrossRef]
27. Ueda K, Ueyama T, Oka M, Ito T, Tsuruo Y, Ichinose M. Polaprezinc (Zinc L-carnosine) is a potent inducer of anti-oxidative stress enzyme, heme oxygenase (HO)-1 - a new mechanism of gastric mucosal protection. J Pharmacol Sci. 2009 Jul;110(3):285-94. Epub 2009 Jun 19. [PubMed] [CrossRef]
28. Kang JW, Lee SM. Melatonin inhibits type 1 interferon signaling of toll-like receptor 4 via heme oxygenase-1 induction in hepatic ischemia/reperfusion. J Pineal Res. 2012 Aug;53(1):67-76. [CrossRef].

Received: 25 February 2015
Published online: 21 May 2015

back to Online Journal