AKRİLAMİDE MARUZ KALAN SIÇANLARIN KALP DOKUSU ÜZERİNDE SELENYUMUN KORUYUCU ROLÜ

Öz

Amaç Akrilamid (ACR), farklı endüstriyel alanlarda yaygın olarak kullanılan zararlı organik reaktif bir bileşiktir. Selenyum (SEL), hem hayvanlarda hem de insan organizmalarında meydana gelen bazı kimyasal ve enzimatik reaksiyonlarda yer alan ve eksikliği durumunda kardiyovasküler sistem gibi birçok sistemde bazı rahatsızlıklara neden olabilen bir eser elementtir. Bu çalışmanın amacı, sıçanlarda deneysel olarak oluşturulan ACR toksisitesinde SEL'in kalp dokusu üzerinde koruyucu bir etkisinin olup olmadığını araştırmaktır. Gereç ve Yöntem Toplam 28 sıçan rastgele ve eşit olarak dört gruba ayrıldı: Kontrol, SEL, ACR, SEL + ACR. Çalışma sonunda kan örneklerinden kreatin kinaz MB (CKMB), laktat dehidrojenaz (LDH) ve iskemi modifiye albümin (IMA) gibi kardiyak belirteçler ile kalp dokusundan toplam oksidan durumu (TOS), toplam antioksidan durumu (TAS) ve oksidatif stres indeksi (OSI) gibi oksidatif stres belirteçlerinin analizleri yapıldı. Ayıca kalp kesitlerinde immünohistokimyasal yöntemler kullanılarak indüklenebilir nitrik oksit sentaz (iNOS) aktiviteleri belirlendi. Bulgular ACR + SEL grubunda, ACR grubuna göre TOS, OSI, CKMB, LDH, IMA düzeylerinde anlamlı düşüş ve TAS düzeyinde önemli artış gözlemlendi. Kalp dokusu kesitlerinin histopatolojik ve immünhistokimyasal değerlendirmesinde; ACR grubunda kalp kası liflerinde düzensizlik, kas lifleri arasında bağ dokusu artışı ve kas liflerinde düzensiz eozinofili tespit edildi. SEL uygulanan gruplarda ACR grubuna göre histopatolojik bulgularda azalma gözlendi. iNOS immünreaktiviteleri; ACR grubunda orta düzeyde ekspresyon gözlenirken, ACR + SEL grubunda daha zayıf bir ekspresyon gözlendi. Sonuç ACR'nin sıçanların kalp dokusunda çeşitli metabolik yollarla hasara yol açtığını ve bu hasarın SEL verilen gruplarda tersine döndürüldüğünü belirledik.

Anahtar Kelimeler

• Selenyum
• akrilamid
• antioksidan
• sıçan

PROTECTIVE ROLE OF SELENIUM ON THE HEART OF RATS EXPOSED ACRYLAMIDE

Öz

Objective Acrylamide (ACR) is a harmful organic reactive compound widely used in different industrial fields. Sele- nium (SEL) is a trace element that takes part in some chemical and enzymatic reactions in both animals and human organisms and can cause some disorders in many systems such as the cardiovascular system in case of deficiency. The aim of this study is to investigate whether SEL has a protective effect on cardiac tissue in experimentally induced ACR toxicity in rats. Material and Method A total of 28 rats were randomly and equally divided into four groups: Control, SEL, ACR, SEL + ACR. At the end of the study, cardiac markers such as creatine kinase MB (CKMB), lactate dehydrogenase (LDH) and ischemia-modified albumin (IMA) from blood samples were measured. Oxidative stress markers such as total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) in heart tissue were analyzed. In addition, inducible nitric oxide synthase iNOS activities were determined in heart sections using immunohistochemical methods. Results The ACR + SEL group showed a significant decrease in TOS, OSI, CKMB, LDH, IMA levels and significant increase in TAS level compared to the ACR group. In histopathological and immunohistochemical evaluation of the heart sections; Disorganization in cardiac muscle fibers, increased connective tissue between muscle fibers and irregular eosinophilia in muscle fibers were detected in ACR group. A decrease in histopathological findings was observed in the SEL treated groups compared to the ACR group. iNOS immunoreactivities; moderate marking was observed in the ACR group sections, while poor marking was observed in the ACR + SEL group. Conclusion We determined that ACR caused damage to the heart tissue of rats through various metabolic pathways and that these damages were reversed in the groups given the SEL.

Anahtar Kelimeler

• Selenium
• acrylamide
• antioxidant
• rat

Kaynakça

1. 1. Semla M, Goc Z, Martiniaková M, Omelka R, Formicki G. Acrylamide: a common food toxin related to physiological functions and health. Physiological research. 2017;66(2):205-17.
2. 2. Smith CJ, Perfetti TA, Rumple MA, Rodgman A, Doolittle DJ. "IARC group 2A Carcinogens" reported in cigarette mainstream smoke. Food Chem Toxicol. 2000;38(4):371-83.
3. 3. Huang M, Jiao J, Wang J, Xia Z, Zhang Y. Characterization of acrylamide-induced oxidative stress and cardiovascular toxicity in zebrafish embryos. Journal of hazardous materials. 2018;347:451-60.
4. 4. Marković J, Stošić M, Kojić D, Matavulj M. Effects of acrylamide on oxidant/antioxidant parameters and CYP2E1 expression in rat pancreatic endocrine cells. Acta histochemica. 2018;120(2):73-83.
5. 5. Ali MA, Aly EM, Elawady AI. Effectiveness of selenium on acrylamide toxicity to retina. International journal of ophthalmology. 2014;7(4):614-20.
6. 6. Pan X, Wu X, Yan D, Peng C, Rao C, Yan H. Acrylamide-induced oxidative stress and inflammatory response are alleviated by N-acetylcysteine in PC12 cells: Involvement of the crosstalk between Nrf2 and NF-κB pathways regulated by MAPKs. Toxicology letters. 2018;288:55-64.
7. 7. Agarwal R, Behari JR. Effect of selenium pretreatment in chronic mercury intoxication in rats. Bulletin of environmental contamination and toxicology. 2007;79(3):306-10.
8. 8. Broome CS, McArdle F, Kyle JA, Andrews F, Lowe NM, Hart CA, et al. An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. The American journal of clinical nutrition. 2004;80(1):154-62.

9. 9. Gouazé V, Mirault ME, Carpentier S, Salvayre R, Levade T, Andrieu-Abadie N. Glutathione peroxidase-1 overexpression prevents ceramide production and partially inhibits apoptosis in doxorubicin-treated human breast carcinoma cells. Molecular pharmacology. 2001;60(3):488-96.
10. 10. Tapiero H, Townsend DM, Tew KD. The antioxidant role of selenium and seleno-compounds. Biomed Pharmacother. 2003;57(3-4):134-144.
11. 11. Gunes S, Sahinturk V, Uslu S, Ayhanci A, Kacar S, Uyar R. Protective Effects of Selenium on Cyclophosphamide-Induced Oxidative Stress and Kidney Injury. Biol Trace Elem Res. 2018;185(1):116-123.
12. 12. Duntas LH. Selenium and inflammation: underlying anti-inflammatory mechanisms. Horm Metab Res. 2009;41(6):443-7.
13. 13. Ahrens I, Ellwanger C, Smith BK, Bassler N, Chen YC, Neudorfer I, et al. Selenium supplementation induces metalloproteinase- dependent L-selectin shedding from monocytes. J Leukoc Biol. 2008;83(6):1388-95.
14. 14. Cao YZ, Weaver JA, Reddy CC, Sordillo LM. Selenium deficiency alters the formation of eicosanoids and signal transduction in rat lymphocytes. Prostaglandins Other Lipid Mediat. 2002;70(1-2):131-43.
15. 15. Gunes S, Sahinturk V, Karasati P, Sahin IK, Ayhanci A. Cardioprotective Effect of Selenium Against Cyclophosphamide-Induced Cardiotoxicity in Rats. Biological trace element research. 2017;177(1):107-14.
16. 16. Dayal S, Blokhin IO, Erger RA, Jensen M, Arning E, Stevens JW, et al. Protective vascular and cardiac effects of inducible nitric oxide synthase in mice with hyperhomocysteinemia. PLoS One. 2014;9(9):e107734.
17. 17. Shah AM. Inducible nitric oxide synthase and cardiovascular disease. Cardiovasc Res. 2000;45(1):148-55.
18. 18. Viaro F, Nobre F, Evora PR. Expression of nitric oxide synthases in the pathophysiology of cardiovascular diseases. Arq Bras Cardiol. 2000;74(4):380-93.
19. 19. Lee J, Bae EH, Ma SK, Kim SW. Altered Nitric Oxide System in Cardiovascular and Renal Diseases. Chonnam Med J. 2016;52(2):81-90.
20. 20. Lind M, Hayes A, Caprnda M, Petrovic D, Rodrigo L, Kruzliak P, et al. Inducible nitric oxide synthase: Good or bad? Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2017;93:370-5.
21. 21. Varadharaj S, Porter K, Pleister A, Wannemacher J, Sow A, Jarjoura D, et al. Endothelial nitric oxide synthase uncoupling: a novel pathway in OSA induced vascular endothelial dysfunc- tion. Respir Physiol Neurobiol. 2015;207:40-7.
22. 22. Ghorbel I, Chaâbane M, Boudawara O, Kamoun NG, Boudawara T, Zeghal N. Dietary unsaponifiable fraction of extra virgin olive oil supplementation attenuates lung injury and DNA damage of rats co-exposed to aluminum and acrylamide. Environ Sci Pollut Res Int. 2016;23(19):19397-408.
23. 23. Ghorbel I, Khemakhem M, Boudawara O, Marrekchi R, Jamoussi K, Ben Amar R, et al. Effects of dietary extra virgin olive oil and its fractions on antioxidant status and DNA damage in the heart of rats co-exposed to aluminum and acrylamide. Food Funct. 2015;6(9):3098-108.
24. 24. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein- dye binding. Anal Biochem. 1976;72:248-54.
25. 25. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37(4):277-85.
26. 26. Karakus E, Halici Z, Albayrak A, Polat B, Bayir Y, Kiki I, et al. Agomelatine: an antidepressant with new potent hepatoprotective effects on paracetamol-induced liver damage in rats. Hum Exp Toxicol. 2013;32(8):846-57.
27. 27. Nežić L, Škrbić R, Amidžić L, Gajanin R, Kuča K, Jaćević V. Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression. Sci Rep. 2018;8(1):14652.
28. 28. United States Environmental Protection Agency. National primary drinking water regulations [Internet]. EPA USA. 2009 [cited 8 August 2022]. Available from: https://www.epa.gov/sites/ default/files/2016-06/documents/npwdr_complete_table.pdf
29. 29. Baum M, Loeppky RN, Thielen S, Eisenbrand G. Genotoxicity of glycidamide in comparison to 3-N-nitroso-oxazolidin-2-one. J Agric Food Chem. 2008;56(15):5989-93.
30. 30. Rayburn JR, Friedman M. L-cysteine, N-acetyl-L-cysteine, and glutathione protect Xenopus laevis embryos against acrylamide- induced malformations and mortality in the frog embryo teratogenesis assay. J Agric Food Chem. 2010;58(20):11172-8.
31. 31. Doerge DR, Gamboa da Costa G, McDaniel LP, Churchwell MI, Twaddle NC, Beland FA. DNA adducts derived from administration of acrylamide and glycidamide to mice and rats. Mutat Res. 2005;580(1-2):131-141.
32. 32. Ghanayem BI, McDaniel LP, Churchwell MI, Twaddle NC, Snyder R, Fennell TR, et al. Role of CYP2E1 in the epoxidation of acrylamide to glycidamide and formation of DNA and hemoglobin adducts. Toxicol Sci. 2005;88(2):311-318.
33. 33. Klaunig JE. Acrylamide carcinogenicity. J Agric Food Chem. 2008;56(15):5984-5988.
34. 34. Mei N, McDaniel LP, Dobrovolsky VN, Guo X, Shaddock JG, Mittelstaedt RA, et al. The genotoxicity of acrylamide and glycidamide in big blue rats. Toxicol Sci. 2010;115(2):412-421.
35. 35. Arthur JR, McKenzie RC, Beckett GJ. Selenium in the Immune System. J Nutr. 2003;133(5):1457S-9S.
36. 36. Maggini S, Wintergerst ES, Beveridge S, Hornig DH. Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses. Br J Nutr. 2007;98 Suppl 1:S29-S35.
37. 37. Zeng H. Selenium as an essential micronutrient: roles in cell cycle and apoptosis. Molecules. 2009;14(3):1263-1278.
38. 38. Tinggi U. Selenium: its role as antioxidant in human health. Environ Health Prev Med. 2008;13(2):102-108.
39. 39. Kushwah A, Boreddy Shivanandappa T, Singh T. Quercetin Attenuates Oxidative Stress, Inflammation and Cardiac Dysfunction in Acrylamide-Induced Cardiotoxicity. Acta Pol Pharm - Drug Res. 2020;77.
40. 40. Malyar RM, Naseri E, Li H, Ali I, Farid RA, Liu D, et al. Hepatoprotective Effects of Selenium-Enriched Probiotics Supplementation on Heat-Stressed Wistar Rat Through Anti-Inflammatory and Antioxidant Effects. Biol Trace Elem Res. 2021;199(9):3445-3456.
41. 41. Ilhan I, Asci H, Tepebasi MY, Imeci OB, Sevuk MA, Temel EN, et al. Selenium exerts protective effects on inflammatory cardiovascular damage: molecular aspects via SIRT1/p53 and Cyt-c/Cas-3 pathways. Mol Biol Rep. 2023;50(2):1627-1637.
42. 42. Walters B, Hariharan V, Huang H. Dietary levels of acrylamide affect rat cardiomyocyte properties. Food Chem Toxicol. 2014;71:68-73.
43. 43. Abdel-Moneim AM, Elsawy H, Alzahrani AM, Ali A, Mahmoud O. Silymarin Ameliorates Acrylamide-Induced Hyperlipidemic Cardiomyopathy in Male Rats. Biol Med Res Internat. 2019;2019:4825075
44. 44. Soudani N, Troudi A, Bouaziz H, Ben Amara I, Boudawara T, Zeghal N. Cardioprotective effects of selenium on chromium (VI)-induced toxicity in female rats. Ecotoxicol Environ Saf. 2011;74(3):513-520.
45. 45. Onopiuk B, Onopiuk P, Dąbrowska Z, Dąbrowska E, Pietruska M, Car H. Effect of Metronidazole on the Oxidoreductive Processes in the Submandibular and Parotid Glands in Experimental Research. Oxid Med Cell Longev. 2018;2018:7083486.
46. 46. Yuksel M, Ates I, Kaplan M, et al. Is Oxidative Stress Associated with Activation and Pathogenesis of Inflammatory Bowel Disease?. J Med Biochem. 2017;36(4):341-348.
47. 47. Taskin E, Dursun N. The protection of selenium on adriamycin- induced mitochondrial damage in rat. Biol Trace Elem Res. 2012;147(1-3):165-171.
48. 48. Donmez DB, Kacar S, Bagci R, Sahinturk V. Protective effect of carnosic acid on acrylamide-induced liver toxicity in rats: Mechanistic approach over Nrf2-Keap1 pathway [published online ahead of print, 2020 May 8]. J Biochem Mol Toxicol. 2020;e22524.
49. 49. Farag OM, Abd-Elsalam RM, Ogaly HA, Ali SE, El Badawy SA, Alsherbiny MA, et al. Metabolomic Profiling and Neuroprotective Effects of Purslane Seeds Extract Against Acrylamide Toxicity in Rat's Brain. Neurochem Res. 2021;46(4):819-842.
50. 50. Kacar S, Sahinturk V, Tomsuk O, Kutlu HM. The effects of thymoquinone and quercetin on the toxicity of acrylamide in rat glioma cells. J Biochem Mol Toxicol. 2022;36(4):e22992.
51. 51. Cinelli MA, Do HT, Miley GP, Silverman RB. Inducible nitric oxide synthase: Regulation, structure, and inhibition. Med Res Rev. 2020;40(1):158-189.
52. 52. Wei Q, Li J, Li X, Zhang L, Shi F. Reproductive toxicity in acrylamide- treated female mice. Reprod Toxicol. 2014;46:121-128.
53. 53. Kim K. Effect of subchronic acrylamide exposure on the expression of neuronal and inducible nitric oxide synthase in rat brain. J Biochem Mol Toxicol. 2005;19(3):162-168.
54. 54. Tian LP, Zhang S, Xu L, Li W, Wang Y, Chen SD, et al. Selenite benefits embryonic stem cells therapy in Parkinson's disease. Curr Mol Med. 2012;12(8):1005-1014.
55. 55. Kassab RB, Elbaz M, Oyouni AAA, Mufti AH, Theyab A, Al-Brakati A, et al. Anticolitic activity of prodigiosin loaded with selenium nanoparticles on acetic acid-induced colitis in rats. Environ Sci Pollut Res Int. 2022;29(37):55790-55802.