GIDA KATKI MADDESİ SODYUM BENZOATIN OKSİDATİF STRES VE GENOTOKSİSİTE ÜZERİNE ETKİLERİNİN ARAŞTIRILMASI

Öz

Amaç Son yıllarda gıda katkı maddelerinin kullanımında belirgin artış vardır. Doğumdan ölüme kadar maruz kalınan bu maddelerin, insanlarda uzun süreli tüketime bağlı olarak oluşturabileceği yan etkiler oldukça önem kazanmıştır. Çalışmamızda özellikle puberte öncesi sıçanlarda sodyum benzoata maruziyetin oksidatif stres ve genotoksisite açılarından değerlendirilmesini amaçladık. Gereç ve Yöntem Kırk iki adet, 4 haftalık erkek sıçan, kontrol (n=14), deney 1 (Acceptable Daily Intake (ADI) dozunda sodyum benzoat, n=14) ve deney 2 (No Advers Effect Level (NOAEL) dozunda sodyum benzoat, n=14) grupları şeklinde 3 gruba ayrılmıştır. Altı hafta süresince oral gavaj uygulanmıştır. Çalışma sonunda sakrifiye edilen sıçanların kan örneklerinden biyokimyasal parametreler (glukoz, kreatinin, AST, ALT, ALP, lipid profili, total protein, albümin), total oksidan status (TOS), total antioksidan status (TAS), iskemi modifiye albümin (İMA) ölçülmüş ve Comet yöntemi ile DNA hasarı değerlendirilmiştir. Ölçülen TOS ve TAS parametrelerinden oksidatif stres indeksi (OSİ) hesaplanmıştır. Bulgular NOAEL dozu sodyum benzoat uygulanan sıçanlarda ALT ve kreatinin seviyeleri yükselmiştir. Ayrıca TOS, IMA ve OSİ seviyeleri NOAEL grubunda yüksek iken TAS seviyeleri düşük bulunmuştur. Bunlara ek olarak NOAEL dozunda sodyum benzoat DNA hasarına yol açmıştır. Sonuç Çalışmamızda, prepubertal dönem sıçanlarda ADI dozunda sodyum benzoat uygulamasının, olumsuz bir etkisi gözlemlenmemiştir. Diğer taraftan NOAEL dozunda sodyum benzoat uygulamasının böbrek ve karaciğer fonksiyonlarını bozduğunu ve oksidatif stres ile genotoksisiteye yol açabileceği ortaya konmuştur.

Anahtar Kelimeler

• Comet
• Gıda katkı maddesi
• Oksidatif stres
• Sodyum benzoat

INVESTIGATION OF THE EFFECTS OF FOOD ADDITIVE SODIUM BENZOATE ON OXIDATIVE STRESS AND GENOTOXICITY

Öz

Objective Recently, there has been a significant increase in the use of food additives. Generation of possible side effects depending on the long-term consumption of these substances from birth to death has gained importance in humans. In our study, we aimed to evaluate the exposure to sodium benzoate in terms of oxidative stress and genotoxicity, especially in prepubertal rats. Material and Method In our study, 42 male rats (4 weeks-old) divided into three groups as the control (n=14), experiment 1 (sodium benzoate Acceptable Daily Intake (ADI) dose, n=14) and experiment 2 (sodium benzoate No Advers Effect Level (NOAEL)dose, n=14) groups and sodium benzoate was administration by oral gavage for 6 weeks. At the end of the study, rats were sacrified and biochemical parameters (glucose, creatinine, AST, ALT, ALP, lipid profile, total protein, albumin), total oxidant status (TOS), total antioxidant status (TAS), ischemia modified albumin (IMA) were measured, and DNA damage was evaluated by Comet analysis. Oxidative stress index (OSI) was calculated from the TOS and TAS parameters. Results ALT and creatinine levels were increased with the NOAEL dosage of sodium benzoate. In addition, TOS, IMA and OSI levels were elevated, while TAS levels were decreased in the NOAEL group. Also, NOAEL dose of sodium benzoate significantly caused DNA damage. Conclusions In our study, no adverse effect was observed in the administration of sodium benzoate at the dose of ADI in prepubertal rats. On the other hand, we found that NOAEL dose of sodium benzoate impairs kidney and liver functions and causes oxidative stress and genotoxicity.

Anahtar Kelimeler

• Comet
• Food additive
• Oxidative stress
• Sodium benzoate

Kaynakça

1. 1. Ünlütürk A, Turantaş F. Gıda Mikrobiyolojisi. Mengi Tan Basımevi, 1. Baskı. ISBN 975-483-383-4, İzmir; 1998.
2. 2. Coşkun F. Gıdalarda bulunan doğal koruyucular. Gıda Teknolojileri Elektronik Dergisi 2006; (2): 27-33.
3. 3. Özdemir H, Turhan AB, Arıkoğlu H. Potasyum sorbat, sodyum benzoat ve sodyum nitrit'in genotoksik etkilerinin araştırılması. European Journal of Basic Medical Science. 2012;2:34-40.
4. 4. Additives EPoF, Sources N. Scientific Opinion on the re‐evaluation of benzoic acid (E 210), sodium benzoate (E 211), potassium benzoate (E 212) and calcium benzoate (E 213) as food additives. EFSA Journal. 2016;14(3):4433.
5. 5. World Health Organization. Evaluation of certain food additives and contaminants [Internet]. WHO Technical Report Series 909. 2002 [cited 15 January 2022]. Available from: https://apps. who.int/iris/bitstream/handle/10665/42578/WHO_TRS_909. pdf?sequence=1.
6. 6. Çalışır ZE, Çalışkan D. Food additives and effects on the human health. Journal of Faculty of Pharmacy of Ankara University. 2003;32(3):193-206.
7. 7. United States Environmental Protection Agency. Provisional Peer Reviewed Toxicity Values for Benzoic Acid. [cited 15 January 2022]. Available from https://nepis.epa.gov/Exe/ZyPDF. cgi/P1010QFV.PDF?Dockey=P1010QFV.PDF
8. 8. Kubota K, Ishizaki T. Dose-dependent pharmacokinetics of benzoic acid following oral administration of sodium benzoate to humans. European journal of clinical pharmacology. 1991;41(4):363-8.

9. 9. Feillet F, Leonard J. Alternative pathway therapy for urea cycle disorders. Journal of inherited metabolic disease. 1998;21(1):101-11.
10. 10. Tuormaa TE. The adverse effects of food additives on health: a review of the literature with a special emphasis on childhood hyperactivity. Journal of Orthomolecular Medicine. 1994;9:225.
11. 11. Coyerly J, Peters L, Whittle E, Basketter D. Susceptibility to skin stinging, non‐immunologic contact urticaria and acute skin irritation; is there a relationship? Contact dermatitis. 1998;38(2):90-5.
12. 12. Piper JD, Piper PW. Benzoate and sorbate salts: a systematic review of the potential hazards of these invaluable preserva- tives and the expanding spectrum of clinical uses for sodium benzoate. Comprehensive reviews in food science and food safety. 2017;16(5):868-80.
13. 13. Darch M, Martyn D, Ngo K, Jack MM. An updated estimate of benzoate intakes from non-alcoholic beverages in Canada and the United States. Food Additives & Contaminants: Part A. 2021;38(5):701-17.
14. 14. Klisic A, Kavaric N, Vujcic S, Spasojevic-Kalimanovska V, Kotur- Stevuljevic J, Ninic A. Total oxidant status and oxidative stress index as indicators of increased Reynolds Risk Score in postmenopausal women. Eur Rev Med Pharmacol Sci. 2020;24(19):10126-33.
15. 15. Özcan O, Erdal H, Çakırca G, Yönden Z. Oksidatif stres ve hücre içi lipit, protein ve DNA yapıları üzerine etkileri. Journal of Clinical and Experimental Investigations. 2015;6(3).
16. 16. Savci U, Senel E, Oztekin A, Sungur M, Erel O, Neselioglu S. Ischemia-modified albumin as a possible marker of oxidative stress in patients with telogen effluvium. Anais Brasileiros de Dermatologia. 2020;95:447-51.
17. 17. Mülazımoğlu S, İde T, Aslan S. Ratlarda üreme. Yücel O (Editör) Küçük deney hayvanlarından rat Ankara: J Clin Anal Med. 2012:39-44.
18. 18. Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental cell research. 1988;175(1):184-91.
19. 19. Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry. 2005;38(12):1103-11.
20. 20. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical biochemistry. 2004;37(4):277-85.
21. 21. Bar–Or D, Lau E, Winkler JV. A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia— a preliminary report. The Journal of emergency medicine. 2000;19(4):311-5.
22. 22. Gardner LK, Lawrence GD. Benzene production from decarboxylation of benzoic acid in the presence of ascorbic acid and a transition-metal catalyst. Journal of Agricultural and Food Chemistry. 1993;41(5):693-5.
23. 23. Gutknecht J. Aspirin, acetaminophen and proton transport through phospholipid bilayers and mitochondrial membranes. Molecular and cellular biochemistry. 1992;114(1):3-8.
24. 24. Halliwell B, Gutteridge JM. Free radicals in biology and medicine: Oxford university press, USA; 2015.
25. 25. Oyewole OI, Dere FA, Okoro OE. Sodium benzoate mediated hepatorenal toxicity in wistar rat: Modulatory effects of azadirachta indica (neem) leaf. European Journal of Medicinal Plants. 2012;2(1):11.
26. 26. Efekemo O, Essien EB, Akaninwor JO. The Effect of Oral Intake of Sodium Benzoate on the Activity of Liver Marker Enzymes and Electrolyte Level of the Wistar Albino Rats. Asian Food Science Journal. 2019;11(2):1-9.
27. 27. Piper PW. Yeast superoxide dismutase mutants reveal a pro-oxidant action of weak organic acid food preservatives. Free Radical Biology and Medicine. 1999;27(11-12):1219-27.
28. 28. Piper PW. Resistance of yeasts to weak organic acid food preservatives. Advances in applied microbiology. 77: Elsevier; 2011. p. 97-113.
29. 29. Khan IS, Dar KB, Ganie SA, Ali MN. Toxicological impact of sodium benzoate on inflammatory cytokines, oxidative stress and biochemical markers in male Wistar rats. Drug and Chemical Toxicology. 2020:1-10.
30. 30. Yetuk G, Pandir D, Bas H. Protective role of catechin and quercetin in sodium benzoate-induced lipid peroxidation and the antioxidant system in human erythrocytes in vitro. The Scientific World Journal. 2014;2014.
31. 31. Jena I, Nayak SR, Behera S, Singh B, Ray S, Jena D, et al. Evaluation of ischemia-modified albumin, oxidative stress, and antioxidant status in acute ischemic stroke patients. Journal of natural science, biology, and medicine. 2017;8(1):110.
32. 32. Roy D, Quiles J, Gaze D, Collinson P, Kaski J, Baxter G. Role of reactive oxygen species on the formation of the novel diagnostic marker ischaemia modified albumin. Heart. 2006;92(1):113-4.
33. 33. Cooke MS, Evans MD, Dizdaroglu M, Lunec J. Oxidative DNA damage: mechanisms, mutation, and disease. The FASEB Journal. 2003;17(10):1195-214.
34. 34. Hu JJ, Dubin N, Kurland D, Ma B-L, Roush GC. The effects of hydrogen peroxide on DNA repair activities. Mutation Research/ DNA Repair. 1995;336(2):193-201.
35. 35. Zengin N, Yüzbaşıoğlu D, Ünal F, Yılmaz S, Aksoy H. The evaluation of the genotoxicity of two food preservatives: sodium benzoate and potassium benzoate. Food and Chemical Toxicology.2011;49(4):763-9.
36. 36. Saatci C, Erdem Y, Bayramov R, Akalın H, Tascioglu N, Ozkul Y. Effect of sodium benzoate on DNA breakage, micronucleus formation and mitotic index in peripheral blood of pregnant rats and their newborns. Biotechnology & Biotechnological Equipment. 2016;30(6):1179-83.
37. 37. Mpountoukas P, Vantarakis A, Sivridis E, Lialiaris T. Cytogenetic study in cultured human lymphocytes treated with three commonly used preservatives. Food and Chemical Toxicology. 2008;46(7):2390-3.