Florun Serbest Radikaller, Reaktif Oksijen Türleri ve Oksidatif Stres ile İlişkileri

Flor halojen ailesinin bir üyesi olup elektronegatifliği yüksek bir elementtir. Florun organizmaya ve hücre içerisine girişiylesüper oksit üretimi artar. Bunun sonucunda ortaya çıkan hidrojen peroksit, peroksinitrit ve hidroksil radikalleri florun reaktifoksijen türleri (ROS) ile ilişkisinde belirleyici rol oynar. ROS’daki artış lipid, protein ve DNA moleküllerinde yıkımlanmaya sebepolur. Florid İle temas sonucunda vücutta stres cevabı faktörlerinde, sinyal transdüksiyon bileşiklerinde, ve apopitozisle ilişkiliproteinleri kodlayan gen ekspresyon düzeylerinde artış ortaya çıkar. Florun hücresel düzeydeki bu etkilerinindeğerlendirilmesi, Türkiye’de var olan florozis sorununa yeni çözüm önerilebilmesi açısından önem arz etmektedir.Ülkemizde, bugüne kadar yapılan çalışmalarda Muğla, Eskişehir, Kırşehir, Çorum, Ankara, Konya, Hatay, Van ve Ağrı illerindesu, toprak, bitki, koyun idrarı, diş ve kemik örneklerinde flor düzeyleri belirlenmiş ve flor zehirlenmesi hakkındadeğerlendirmeler yapılmıştır. Bu kapsamda flor'un canlı organizmadaki etkisine hücresel düzeyde değinilerek flor'un serbestradikaller, ROS ve oksidatif stres oluşumuna etkisi değerlendirilmiştir.

Free Radicals, Reactive Oxygen Species and Relationship with Oxidative Stress

Fluorine is a highly reactive chemical element and a member of halogen family. Fluorides entry into the organismand cells that increases the production of superoxide. Superoxide generates hydrogen peroxide, peroxynitrite, and hydroxylradicals, and plays a decisive role at the relationship between fluorine and reactive oxygen species (ROS). The increase in ROScauses oxidative damage in lipid, protein, and DNA molecules. As a result of contact with fluoride, an increase in geneexpression levels encoding stress related response factors in the body, signal transduction compounds, and apoptosis relatedproteins occurs. Assessment of these effects at the cellular level of fluor is important in terms of suggesting a new solutionto the problem of fluorosis in Turkey. Fluoride levels were determined in water, soil, plant and sheep urine, tooth, bonesamples in the areas of Ağrı, Van, Muğla, Eskişehir, Kırşehir, Çorum, Ankara, Hatay in Turkey. Results were evaluated to findout fluor toxicosis. In this review, the effect of fluoride in the living organism is addressed at cellular level, and the effect offluoride on free radicals, ROS and oxidative stress formation is discussed.

___

  • Kaynaklar 1. Şendil, Ç, Bayşu, N. İnsan ve hayvanlardaki Ağrı İli Doğubayazıt ilçesi köylerinde görülen flor zehirlenmesi ve bunun van ili muradiye ilçesi köylerinde de saptamamızla ilgili ilk tebliğ 1973. 2. Ergun HS, Rüssel-Sinn HA., Baysu N., Dündar Y. Studies on the fluoride contents in water and soil, urine, bone and teeth of sheep, and urine of human from eastern and western parts of Turkey. Dtsch. Tierarstl Wschr 1987; 94: 381-440. 3. Fidancı UR, Salmanoğlu B, Maraşlı Ş, Maraşlı N. İç Anadolu Bölgesinde doğal ve endüstriyel florozis ve bunun hayvan sağlığı üzerine etkileri. Tr J Of Veterinary and Animal Scences 1998; 22: 537-544. 4. Altıntaş A, Fidancı UR, Sel T, Duru Ö, Başsatan A. Doğal ve endüstriyel florozisli koyunlarda böbrek fonksiyonu ve serum protein elektroforezi. Ankara Üniv. Vet. Fak. Derg, 2000; 47: 105-114. 5. Işıklı B, Kalyoncu C, Metintaş S, Demir TA. Eskişehir yöresindeki içme sularında florür düzeyleri. Ekoloji Çevre dergisi 2000; 9, 36: 28-30. 6. Erdoğan, S. Hatay bölgesi içme suyu örneklerinde flor düzeyleri. Vet Bil. Derg 2002; 18: 1-2. 7. Öksüz S. Pöhrenk (Kırşehir) sıcak su kaynaklarının hidrojeokimyasal incelemesi. Yüksek Lisans Tezi, Çukurova Üniversitesi Fen Bilimleri Enstitüsü, 2006. 8. Barbier O, Arreolar-Mendoza L, Del Roza LM. Molecular mechanisms of fluoride toxicity. Chem-Biological Interactions 2010; 188: 319-333. 9. Sivanandham V. Free radicals in the health and diseaese–a mini review. Pharmacologyonline 2011; 1: 1062-1077. 10. Ercan N, Fidancı UR. Oksidatif DNA hasar ürünleri ve hastalıklar. Dicle Üniv. Vet. Fak. Derg 2012; 2: 40-57. 11. Kargın F, Fidancı UR. Böbrek hastalıklı köpeklerde antioksidatif metabolizma. Türk. J. Vet. Anim. Sci., 2001; 25: 607-613. 12. Pisoschi AM, Negulescu GP. Methods for Total Antioxidant Activity Determination: A Review. Biochem & Anal Biochem 2011; 1: 1-10. 13. Durackova Z, Some current insights into oxidative stress. Physiol. Res 2010; 59 4: 459-469. 14. Chatterjee M, Saluja R, Kanneganti S, Chinta S, Dikshit M, Biochemical and molecular evaluation of neutrophil nos in spontaneously hypersensitive rats. Cell Mol. Biol 2007; 53: 84-93. 15. Frei B. ‘Reactive oxygen species and antioxidant vitamins Linus Pauling Institute. Oregon State University’. http://lpi.oregonstate.edu/f-w97/reactive.html. 22.05.2016 16. Genestra M. Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Review. Cell Signal 2007; 19: 1807-1819. 17. Pacher P, Beckman JS, Liaudet L, Nitric oxide and peroxynitrite in health and disease. Physiol. Rev 2007; 87: 315-424. 18. Willcox JK, Ash SL, Catignani GL. Antioxidants and prevention of chronic disease. Review. Crit. Rev. Food. Sci. Nutr 2004; 44: 275-295. 19. Pham-Huy LA, He H, Pham-Huy CP. Free radicals, antioxidants in disease and health. International Journal of Biomedical Science 2008; 4, 2: 89-96. 20. Izquierdo-Vega JA, Sánchez-Gutiérrez M, Del Razo LM. Decreased in vitro fertility in male rats exposed to fluoride-induced oxidative stress damage and mitochondrial transmembrane potential loss. Toxicol. Appl. Pharmacol 2008; 230:352-357. 21. Hassan HA, Yousef MI, Mitigating effects of antioxidant properties of black berry juice on sodium fluoride induced hepatotoxicity and oxidative stressinrats, Foodand Chemical Toxicology 2009; 47, 9: 2332-2337. 22. Liu G, Chai C, Cui L, Fluoride causing abnormally elevated serum nitric oxide levels in chicks. Environ Toxicol Pharmacol 2003; 13: 199-204. 23. Mittal M, Flora SJ, Effects of individual and combined exposure to sodium arsenite and sodium fluoride on tissue oxidative stress, Arsenic and fluoride levels in male mice. Chem. Biol. Interact 2006; 162: 128-139. 24. He LF, Chen JG. DNA damage, apoptosis and cell cycle changes induced by fluoride in rat oral mucosal cells and hepatocytes. World Journal of Gastroenterology 2006; 12, 7: 1144-1148. 25. Chouhan S, Flora JS, Effects of fluoride on the tissue oxidative stress and apoptosis in rats: biochemical assays supported by IR spectroscopy data. Toxicology 2008; 254 1-2: 61-67. 26. Chouhan S, Lomash V, Flora JS. Fluorideinduced changes in haem biosynthesis pathway, neurological variables and tissue histopathology of rats, Journal of Applied Toxicology 2010; 30: 63-73. 27. Kısmalı G, Sel T, Paraquat ile oluşturulmuş oksidatif stresin hepg2 hücrelerinde apoptozis üzerine etkisinin araştırılıması. F. Ü. Sağ. Bil. Derg 2012; 26, 2: 79-85. 28. Sun Z, Niu R, Wang B, Jiao Z, Wang J, Zhang J, Wang S, Wang J. Fluoride-induced apoptosis and gene expression profiling in mice sperm in vivo. Archives of Toxicology 2011; 85: 1441-1452. 29. Vani ML, Reddy KP. Effects of fluoride accumulation on some enzymes of brain and gastrocnemius muscle of mice. Fluoride 2000; 33, 1: 17-26. 30. Garcia-Montalvo EA, Reyes-Perez H, Del Razo LM, Fluoride exposure impairs glucose tolerance via decreased insulin expression and oxidative stress. Toxicology 2009; 263:75-83. 31. Nobes CD, Hall A. Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 1995; 81: 53-62. 32. Shivarajashankara YM, Shivashankara AR, Gopalakrishna BP, Rao SH, Oxidative stress in children with endemic skeletal fluorosis. Fluoride 2001; 34: 108-113. 33. Karube H, Nishitai G, Inageda K, Kurosu H, Matsuoka M, NaF activates MAPKs and induces apoptosis in odontoblast-like cells. J Dent Res 009; 88: 461-465. 34. Paul A, Wilson S, Belham CM, Robinson CJM, Scott PH, Gould G W, Plevin R. Stress-activated protein kinases: activation, regulation and function. Cell Signal 1997; 9: 403-410. 35. Ridley W, Matsuoka M. Fluoride-induced cyclooxygenase-2 expression and prostagland in E2 production in A549 human pulmonary epithelial cells. Toxicol. Lett 2009; 188: 180-185. 36. Chlubek D, 2003: Fluoride and oxidative stress. Fluoride, 36, 217-28. 37. Agalakova NI, Gusev GP. Molecular mechanisms of cytotoxicity and apoptosis induced by inorganic fluoride. Cell Biology 2012; 1-16. 38. Shanthakumari D, Srinivasalu S, Subramanian S. Effect of fluoride intoxication on lipidperoxidation and antioxidant status in experimental rats. Toxicology, 2004; 204: 219-228. 39. Sinha M, Manna P, Sil P. A 43kD protein from the herb, Cajanus indicus L., protects against fluoride induced oxidative stress in mice erythrocytes. Pathophysiology 2007; 14: 1, 47-54. 40. Gosh J, Das J, Manna P, Sil PC. Cytoprotective effect of arjunolic acid in response to sodium fluoride mediated oxidative stress and cell death via necrotic pathway. Toxicol In Vitro 2008; 22: 1918-1926. 41. Xu H, Wang CH, Zhao ZT, Zhang WB, Li GS. Role of oxidative stress in osteoblasts exposed to sodium fluoride. Biological Referans1 Sel, T., Ergun, H. Doğu Anadolu’da florozis belirtisi gösteren koyunlarda serum spesifik karaciğer enzimleri ve ALP düzeyi.A.Ü. Vet. Fak. Derg. Col. 39 (1-2) 30-40. 1992 Referans2 Balkan Burcu Menekşe, Kısmalı Görkem, Alpay Merve, Sayıner Serkan, Turan Deniz, Balkan Ali Burak, Salmanoğlu Berrin, Karagül Şeküre Hilal, Sel Tevhide. The effects of vitamin E on antioxidant enzyme activity in HepG2 cells. Kafkas Universitesi Veteriner Fakultesi Dergisi, 22(6) (Yayın No: 3267028) 2016 Referans3 H. Karagül, H.P. Sallmann, U.R. Fidancı, T. Sel, S. Çelik, R. Vural, A. Önal, N.Ünal. The effect of vit E and Selenium deficiency on the roproductive hormones and antioxidative systems in Akkaraman sheep.. deutsch-Türkische Agrarforschung. Redaktion. U. Planck verlag ulrich. E. Grauer. Stuttgart, 383-388, 2000.