Scientific Online Resource System

Scripta Scientifica Medica

Apoptosis as a mechanism for burn-induced gastric mucosal injury

Minka Aleksandrova Hristova, Maria Tzaneva, Ganka Bekyarova, Dariya Chivchibashi

Abstract

ABSTRACT

Introduction: Severe thermal burns disturb tissue homeostasis of many organs, but the exact mechanisms of gastric mucosa changes are not yet clear. Various cellular mechanisms, such as cell activation, mitochondrial dysfunction, free oxygen radicals and cytokine overproduction may be involved in this process.

Aim: The aim of this study was to assess the levels of malondialdehyde (MDA), apoptotic proteins Bax and Bcl-2 in normal gastric mucosa and to test the hypothesis that oxidative stress activation induces apoptotic processes in the stomach after experimental thermal trauma.

Materials and Methods: Under anesthesia, the shaved rats` dorsum was exposed to 90° C bath for 10 s to induce third-degree burn injury, involving 30% of the total body surface area. We determined the tissue level of MDA, a lipid peroxidation marker, by spectrophotometric method and the apoptosis of epithelial cells in gastric mucosa, which was immunohistochemically determined at the level of Bcl-2 and Bax in burn trauma.

Results: The gastric MDA level was higher (p<0.01) in the burned group compared to the control group 24 hours after thermal injury. The gastric mucosa in the treated group showed congestion, degenerative changes in the surface epithelium, focal destruction of glandular epithelium with formation of acute erosions. Bax expressed moderately in epithelial cells, predominantly in the basal parts of the gastric glands, while in the control group protein content was localized in the same region, but it was weak. Bcl-2 protein in the control group revealed nuclear expression in surface epithelium, while in the basal layer of gastric mucosa the expression was moderate and mainly cytoplasmic. In the burned group, Bcl-2 expression was more diffuse, nuclear and cytoplasmic, but cytoplasmic expression was weak.

Conclusion: Thermal skin trauma induces gastric mucosal injury through the activation of lipid peroxidation, increase of pro-apoptotic Bax protein expression and decrease of anti-apoptotic Bcl-2 protein expression in epithelial cells. We suggest that apoptosis is a possible mechanism for structural changes in the gastric mucosa.


Keywords

thermal burns, gastric mucosa, apoptosis, lipid peroxidation

Full Text


References

Çakir B, Yeğen BC. Systemic responses to burn injury. Turk J Med Sci. 2004; 34(4): 215-26.

Markell KW, Renz EM, White CE, Albrecht ME, Blackbourne LH, Park MS, et al. Abdominal complications after severe burns. J Am Coll Surg. 2009;208(5):940-7. doi: 10.1016/j.jamcollsurg.2008.12.023.

Spirt MJ. Stress-related mucosal disease: risk factors and prophylactic therapy. Clin Ther. 2004;26(2):197-213.

Zhu L, Yang ZC, Li A, Cheng DC. Reduced gastric acid production in burn shock period and its significance in the prevention and treatment of acute gastric mucosal lesions. World J Gastroenterol. 2000;6(1):84-8.

Brzozowski T, Konturek PC, Konturek SJ, Pajdo R, Bielanski W, Brzozowska I, et al. The role of melatonin and L-tryptophan in prevention of acute gastric lesions induced by stress, ethanol, ischemia, and aspirin. J Pineal Res. 1997;23(2):79-89.

Suzuki H, Nishizawa T, Tsugawa H, Mogami S, Hibi T. Roles of oxidative stress in stomach disorders. J Clin Biochem Nutr. 2012;50(1):35-9. doi: 10.3164/jcbn.11-115SR.

IÅŸeri SO, Gedik IE, Erzik C, Uslu B, Arbak S, Gedik N, et al. Oxytocin ameliorates skin damage and oxidant gastric injury in rats with thermal trauma. Burns. 2008;34(3):361-9. doi: 10.1016/j.burns.2007.03.022

Sehirli O, Sener E, Sener G, Cetinel S, Erzik C, YeÄŸen BC. Ghrelin improves burn-induced multiple organ injury by depressing neutrophil infiltration and the release of pro-inflammatory cytokines. Peptides. 2008;29(7):1231-40. doi: 10.1016/j.peptides.2008.02.012.

Zeiss CJ. The apoptosis-necrosis continuum: insights from genetically altered mice. Vet Pathol. 2003;40(5):481-95. doi: 10.1354/vp.40-5-481.

Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516. doi: 10.1080/01926230701320337.

Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med. 2010;48(6):749-62. doi: 10.1016/j.freeradbiomed.2009.12.022.

Gravante G, Delogu D, Sconocchia G. "Systemic apoptotic response" after thermal burns. Apoptosis. 2007;12(2):259-70. doi: 10.1007/s10495-006-0621-8

Porter NA, Nixon JR. Isaac R. Cyclic peroxidase and thiobarbituric assay. Biochim Biophys Acta. 1976;441(3):596-9.

Friedl HP, Till GO, Trentz O, Ward PA. Roles of histamine, complement and xanthine oxidase in thermal injury of skin. Am J Pathol. 1989;135(1):203-17.

Parihar A, Parihar MS, Milner S, Bhat S. Oxidative stress and anti-oxidative mobilization in burn injury. Burns. 2008;34(1):6-17. doi: 10.1016/j.burns.2007.04.009.

Armutcu F, Gürel A, HoÅŸnuter M, Pabuçcu O, Altnyazar C. Caffeic acid phenethyl ester improves oxidative erythrocyte damage in a rat model of thermal injury. J Burn Care Rehabil. 2004;25(2):171-8.

Rocha J, Eduardo-Figueira M, Barateiro A, Fernandes A, Brites D, Bronze R, et al. Anti-inflammatory effect of rosmarinic acid and an extract of Rosmarinus officinalis in rat models of local and systemic inflammation. Basic Clin Pharmacol Toxicol. 2015;116(5):398-413. doi: 10.1111/bcpt.12335.

Bekyarova G, Hristova М. Uric acid, thiols and burn-induced oxidative injury of gastric mucosa in rats. Scr Sci Med. 2012; 44 (Suppl 1):31-4.

Sener G, Sehirli O, Velioglu Ogune A, Erean F, Erkainli G, Gedik N, et al. Propylthiouracil (PTU)-induced hypothyroidism alleviates burn-induced multiple organ injury. Burns. 2006;32(6):728-36. DOI: 10.1016/j.burns.2006.01.002.

Kabasakal L, Sener G, Cetinel S, Contuk G, Gedik N, YeÄŸen BC. Burn-induced oxidative injury of the gut is ameliorated by the leukotriene receptor blocker montelukast. Prostaglandins Leukot Essent Fatty Acids. 2005;72(6):431-40. doi: 10.1016/j.plefa.2005.02.008.

Padfield KE, Astrakas LG, Zhang Q, Gopalan S, Dai G, Mindrinos MN, et al. Burn injury causes mitochondrial dysfunction in skeletal muscle. Proc Natl Acad Sci U S A. 2005;102(15):5368-73. doi: 10.1073/pnas.0501211102.

Zang QS, Maass DL, Wigginton JG, Barber RC, Martinez B, Idris AH, et al. Burn serum causes a CD14-dependent mitochondrial damage in primary cardiomyocytes. Am J Physiol Heart Circ Physiol. 2010;298(6):H1951-8. doi: 10.1152/ajpheart.00927.2009.

Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 2012;298:229-317. doi: 10.1016/B978-0-12-394309-5.00006-7.

Weisser SB, McLarren KW, Kuroda E, Sly LM. Generation and characterization of murine alternatively activated macrophages. Methods Mol Biol. 2013;946:225-39. doi: 10.1007/978-1-62703-128-8_14.

Hristova M, Bekyarova G, Tzaneva M. Heme oxygenase 1 expression and oxidative stress - related markers in gastric mucosa in skin burns and protection with melatonin. Trakia Journal of Sciences, 2016; 4:307-13. doi:10.15547/tjs.2016.04.001.

Pacher P, Szabo C. Role of the peroxynitrite-poly(ADP-ribose) polymerase pathway in human disease. Am J Pathol. 2008;173(1):2-13. doi: 10.2353/ajpath.2008.080019.

Brunelle JK, Letai A. Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci. 2009;122(Pt 4):437-41. doi: 10.1242/jcs.031682.

Rastogi R, Sinha R, Sinha RP. Apoptosis: molecular mechanisms and pathogenicity. EXCLI Journal. 2009;8:155-81.

Liu YH, Zhang ZB, Zheng YF, Chen HM, Yu XT, Chen XY, et al. Gastroprotective effect of andrographolide sodium bisulfite against indomethacin-induced gastric ulceration in rats. Int Immunopharmacol. 2015;26(2):384-91. doi: 10.1016/j.intimp.2015.04.025.

Park JH, Jang KJ, Kim CH, Lee YH, Lee SJ, Kim BH, et al. Ganoderma lucidum pharmacopuncture for the treatment of acute gastric ulcers in rats. J Pharmacopuncture. 2014;17(3):40-9. doi: 10.3831/KPI.2014.17.025.

Golbabapour S, Gwaram NS, Al-Obaidi MM, Soleimani AF, Ali HM, Abdul Majid N. Schiff base metal derivatives enhance the expression of HSP70 and suppress BAX proteins in prevention of acute gastric lesion. Biomed Res Int. 2013;2013:703626. doi: 10.1155/2013/703626.

Liu J, Li ZS, Wan XJ, Wang W. Expression and function of apoptosis-related genes Bcl-2/Bax and Fas/Fas L in the course of stress ulcer. Zhonghua Yi Xue Za Zhi. 2003;83(6):504-9.

Bekyarova G, Tzaneva M, Hristova M. Melatonin modulates the expression of Bcl-2 family proteins in liver after thermal injury in rats. Advances in Bioscience and Biotechnology. 2013, (4):41-7. doi: 10.4236/abb.2013.411A2006

Zhou WJ, Zhang C, Liu Y, Liu P, Ma M, Zhang SF. Influence of oxidative stress on apoptosis and expression of bax and bcl-2 of enterocytes in burn rats with delayed resuscitation on the plateau. Zhonghua Shao Shang Za Zhi. 2009;25(4):289-93.

Messaris E, Kekis P, Memos N, Chatzigianni E, Menenakos E, Leandros E, et al. Sepsis: prognostic role of apoptosis regulators in gastrointestinal cells. World J Surg. 2007;31(4):787-94. doi: 10.1007/s00268-005-0742-1.

Jeschke MG, Debroy MA, Wolf SE, Rajaraman S, Thompson JC. Burn and starvation increase programmed cell death in small bowel epithelial cells. Dig Dis Sci. 2000;45(2):415-20.




DOI: http://dx.doi.org/10.14748/ssm.v50i1.4238

Refbacks

About The Authors

Minka Aleksandrova Hristova
Department of Physiology and Pathophysiology
Bulgaria

Medical University of Varna

Maria Tzaneva
Department of General and Clinical Pathology
Bulgaria

Medical University of Varna

Ganka Bekyarova
Department of Physiology and Pathophysiology
Bulgaria

Medical University of Varna

Dariya Chivchibashi
Department of General and Clinical Pathology
Bulgaria

`St. Marina` University Hospital, Varna

Font Size


|