Ayşe Burçin UYUMLU, Haldun Şükrü ERKAL, Haldun Şükrü ERKAL, Kadir BATÇIOĞLU, Meltem SERİN, Neslihan YÜCEL

Farklı Yaşlardaki Ratların Beyin Dokularında Radyasyonla İndüklenen Oksidatif Hasarın Değerlendirilmesi

Anahtar Kelimeler:

Radyoterapi, yaşlanma, oksidan hasar, beyin, serbest radikaller.

Evaluation of Oxidant Injury Induced by Irradiation in Brain Tissues of Rats of Different Ages

Objectives: We aimed to evaluate the age-related changes of oxidative injury in the brain tissues of rats produced by radiotherapy that is widely used on cancer treatment. Study Design: Fifty-five male Wistar albino rats [ages of rats were 1, 4, 12 weeks (n=10) and 1 year (n=5)] were divided into four groups. Irradiation were performed on a Cobalt-60 unit using a single fraction of 8 Gy. The brain tissues were homogenized and divided into two portions. One portion was used for the measurement of the malondialdehyde (MDA). The other portion was used for the measurement of the protein concentration, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) enzyme activities. Results: The SOD activity decreased significantly in 1-week-old rats (p&lt;0.05). The decreases in GSHPx and CAT activities were more obvious in 1-week and 1-year-old rats than that in others. No significant changes were observed in adolescent and adult rats. The MDA levels of all groups increased. The highest MDA levels were seen in 1-year-old rats (p&lt;0.05). Conclusion: Ionizing radiation used in radiotherapy affected antioxidant systems and increased MDA levels. These changes were more in the 1-week and 1-year-old rats than in others. This can be due to incomplete development of many systems in newborn rats and the loss of physiological capacities associated with aging in 1-year-old rats. Turkish Başlık: Farklı Yaşlardaki Ratların Beyin Dokularında Radyasyonla İndüklenen Oksidatif Hasarın Değerlendirilmesi Anahtar Kelimeler: Radyoterapi; yaşlanma; oksidan hasar; beyin; serbest radikaller Amaç: Bu çalışmada, kanser tedavisinde yaygın olarak kullanılan radyoterapinin farklı yaşlardaki ratların beyin dokusunda oluşturduğu oksidatif hasarın değerlendirilmesi amaçlandı. Çalışma Planı: Elli beş Wistar albino tipi erkek rat, 1, 4 ve 12 haftalık (n=10) ve 1 yaş (n=5) olmak üzere dört gruba ayrıldı. Tüm gruptaki ratlara Co-60 cihazı ile 8 Gy tek fraksiyon radyasyon uygulandı. Ratların beyin dokuları homojenize edilerek ikiye ayrıldı. Bir yarısı ile malondialdehid (MDA) ölçümü yapıldı. Diğer yarısından elde edilen süpernatant ile protein miktar tayini yapıldı, süperoksit dismutaz (SOD), katalaz (CAT), glutatyon peroksidaz (GSHPx) aktiviteleri ölçüldü. Bulgular: SOD aktivitesinin 1 haftalık ratlarda anlamlı derecede azaldığı bulundu (p&lt;0.05). GSHPx ve CAT aktivitesindeki azalma 1 haftalık ve 1 yaşındaki ratlarda daha belirgindi. Ergen ve erişkin ratlarda önemli değişmeler olmadı (p&lt;0.05). MDA düzeyinde tüm yaş gruplarında artma gözlendi. En yüksek MDA düzeyi 1 yaşındaki ratlarda gözlendi (p&lt;0.05). Sonuç: Radyoterapide kullanılan iyonize radyasyon antioksidan sistemleri etkilemekte ve doku MDA düzeylerini artırmaktadır. Bu değişiklikler 1 haftalık ve 1 yaşındaki ratlarda daha fazladır. Bu durumun yeni doğan ratlarda henüz birçok sistemin tam olarak yerleşmemiş oluşundan ve 1 yaşındaki ratlarda ise yaşlanmaya bağlı olarak ortaya çıkan fizyolojik kapasitedeki kayıplardan kaynaklandığını söyleyebiliriz.

Keywords:

Radiotherapy; aging; oxidant injury; brain; free radicals,

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Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA, et al. Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicology 2000;148:187-97.
Halliwell B, Gutteridge JM. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 1984;219:1-14.
Riley PA. Free radicals in biology: oxidative stress and the effects of ionizing radiation. Int J Radiat Biol 1994;65:27-33.
Kumar KS, Vaishnav YN, Weiss JF. Radioprotection by antioxidant enzymes and enzyme mimetics. Pharmacol Ther 1988;39:301-9.
Golden TR, Hinerfeld DA, Melov S. Oxidative stress and aging: beyond correlation. Aging Cell 2002;1:117-23.
Yankner BA, Lu T, Loerch P. The aging brain. Annu Rev Pathol 2008;3:41-66.
Kuklei ML, Stvolinskii SL, Boldyrev AA, Gannushkina IV. Lipid peroxidation in the brain of rats differing in resistance to emotional stress. Biull Eksp Biol Med 1994;118:1085-7.
Mihara M, Uchiyama M. Determination of malon- aldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978;86:271-8.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265-75.
McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 1969;244:6049-55.
Luck H. Catalase. In: Bergmeyer HU, Editor. Methods of enzymatic analysis. 2nd ed. New York: Academic Press; 1963. p. 885–8.
Lawrence RA, Burk RF. Glutathione peroxidase activ- ity in selenium-deficient rat liver. Biochem Biophys Res Commun 1976;71:952-8.
Daly JM, Bertagnoli M, De Cosse JJ, Morton DL. Oncology. In: Schwartz SI editor. Principles of sur- gery. New York: McGraw-Hill; 1999. p. 335-45.
Kirkwood TB. Evolution of ageing. Nature 1977;270:301-4.
Ainsworth C, Le Page M. Evolution's greatest mis- takes. New Scientist 2007;195:36-39.
Szweda PA, Camouse M, Lundberg KC, Oberley TD, Szweda LI. Aging, lipofuscin formation, and free radical-mediated inhibition of cellular proteolytic systems. Ageing Res Rev 2003;2:383-405.
Nakamura YK, Omaye ST. Age-related changes of serum lipoprotein oxidation in rats. Life Sci 2004;74:1265-75.
Akman SA, Forrest G, Chu FF, Doroshow JH. Resistance to hydrogen peroxide associated with altered catalase mRNA stability in MCF7 breast can- cer cells. Biochim Biophys Acta 1989;1009:70-4.
Prolla TA, Mattson MP. Molecular mechanisms of brain aging and neurodegenerative disorders: lessons from dietary restriction. Trends Neurosci 2001;24(11 Suppl):S21-31.
Bourre JM, Dumont O, Gumpel M, Cassagne C. Alteration of sulfatide synthesis in control and Trembler mice during Wallerian degeneration and remyelination. Neurochem Pathol 1984;2:153-61.
Hoptman MJ, Davidson RJ. How and why do the two cerebral hemispheres interact? Psychol Bull 1994;116:195-219.
Row BW. Intermittent hypoxia and cognitive func- tion: implications from cronic animal models. In: Roach RC, Wagner PD, Hackett PH, editors. Hypoxia and the circulation. 1st ed. New York: Springer; 2007. p. 51-67.
Schindler MK, Forbes ME, Robbins ME, Riddle DR. Aging-dependent changes in the radiation response of the adult rat brain. Int J Radiat Oncol Biol Phys 2008;70:826-34.
Niwa Y, Ishimoto K, Kanoh T. Induction of superox- ide dismutase in leukocytes by paraquat: correlation with age and possible predictor of longevity. Blood 1990;76:835-41.
Reiss U, Gershon D. Comparison of cytoplasmic superoxide dismutase in liver, heart and brain of aging rats and mice. Biochem Biophys Res Commun 1976;73:255-62.
Im MJ, Hoopes JE. Age-dependent decreases in superoxide dismutase activity in rat skin. J Invest Dermatol 1984;82:437.
Sivonová M, Tatarková Z, Duracková Z, Dobrota D, Lehotský J, Matáková T, et al. Relationship between antioxidant potential and oxidative damage to lip- ids, proteins and DNA in aged rats. Physiol Res 2007;56:757-64.
Niwa Y, Kasama T, Miyachi Y, Kanoh T. Neutrophil chemotaxis, phagocytosis and parameters of reactive oxygen species in human aging: cross-sectional and longitudinal studies. Life Sci 1989;44:1655-64.
Head E, Liu J, Hagen TM, Muggenburg BA, Milgram NW, Ames BN, et al. Oxidative damage increases with age in a canine model of human brain aging. J Neurochem 2002;82:375-81.
Niki E, Yoshida Y, Saito Y, Noguchi N. Lipid peroxi- dation: mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun 2005;338:668-76.