Gonca OZAN, Nurten TÜRKÖZKAN, Barbaros BALABANLI, Filiz SEZEN BİRCAN

ENDOTOKSEMİ MODELİNDE TAURİNİN BEYİN DOKUSU ENERJİ DURUMU VE MALONDİALDEHİT DÜZEYLERİNE ETKİSİ

Taurin pek çok memeli dokusunda ve plazmasında milimolar konsantrasyonlarda bulunan, kükürtiçeren bir β-amino asittir. Çok sayıda in vivo ve in vitro çalışmada hücre koruyucu etkilere sahip olduğugösterilmiş ve bu etkileri genellikle antioksidan rolüne bağlanmıştır. Bu çalışmada, endotoksemi oluşturulankobayların beyin dokularında, taurinin enerji metabolizması ve lipit peroksidasyonu üzerindeki etkilerininbelirlenmesi amaçlanmıştır.Gereç ve Yöntem: 40 adet yetişkin erkek kobay; kontrol, taurin, endotoksemi ve endotoksemi+taurin olmaküzere 4 gruba ayrılmıştır (n=10). Endotoksemi modeli tek doz 4 mg/kg intraperitonal lipopolisakkarit (LPS)enjeksiyonu ile gerçekleştirilmiş, taurin gruplarına eş zamanlı olarak tek doz 300 mg/kg ip taurin uygulanmıştır.Uygulamadan 6 saat sonra, hayvanlar anestezi altında feda edilerek beyin dokuları alınmıştır. DokuATP, ADP, malondialdehit (MDA) ve taurin düzeyleri yüksek performanslı sıvı kromatografisi (HPLC) ile analizedilmiştir.Bulgular: Beyin dokusu ATP/ADP oranı hem endotoksemi hem de endotoksemi+taurin gruplarında, kontrolve taurin grupları ile karşılaştırıldığında istatistiksel olarak anlamlı şekilde azalmıştır. Kontrol grubuyla karşılaştırıldığında,tüm grupların MDA seviyeleri yüksek bulunmuş olup, bunlardan taurin grubundaki artışistatistiksel olarak anlamlı bulunmuştur. Endotoksemi grubunun taurin düzeylerinin ise, kontrol grubu ilekıyaslandığında belirgin bir azalma gösterdiği tespit edilmiştir.Sonuç: Endotokseminin beyin dokusu ATP/ADP oranı ve taurin düzeylerinde önemli bir azalmaya nedenolduğu bulunmuştur. Taurin uygulaması ise herhangi bir antioksidan etki göstermemekle birlikte, bekleneninaksine bu dozda nöronal hasara katkı sağlamıştır. Bu verilere göre, beyin dokusunun korunması içintaurinin daha düşük dozda uygulanması yararlı olabilir ya da taurin uygulaması tüm dozlarda nörotoksiketki gösteriyor olabilir.

Effect of Taurine on Brain Energy Status and Malondialdehyde Levels in Endotoxemia Model

Objectives: Taurine is a sulfur-containing β-amino acid that is found in milimolar concentrations in most mammalian tissues and plasma. It was shown to have cytoprotective effects in many in vitro and in vivo studies and these actions are often attributed to an antioxidant mechanism. The aim of the present study was to determine the effects of taurine on brain energy metabolism and lipid peroxidation under conditions of experimental endotoxemia. Material and Methods: Forty adult male guinea pigs were divided into four groups: control, taurine, endotoxemia, and endotoxemia plus taurine. Taurine (300 mg/kg), lipopolysaccharide (LPS, 4 mg/kg), or taurine plus LPS was administered intraperitoneally. After 6 h of incubation, the animals were killed and brain tissue samples were collected. Tissue ATP, ADP, taurine and malondialdehyde (MDA) levels were measured using high performance liquid chromatography methods. Results: The ATP/ADP ratio decreased in endotoxemia and endotoxemia+taurine group significantly. MDA levels increased in all groups compared to control group. Also taurine group MDA levels were significantly increased in compared to control group. In endotoxemia group, LPS administration significantly decreased taurine levels compare to control group. Conclusion: Endotoxemia decreased brain tissue ATP/ADP ratio and taurine levels. Taurine did not exhibit any antioxidant effect; moreover, it may contribute to neuronal damage at this dose. Thus, we can suggest that lower dose of taurine administration may be beneficial for neuronal protection or adversely taurine administration may have neurotoxic effect at all doses.

PDF

___

Kang YS. Taurine transport mechanism through the bloodbrain barrier in spontaneously hypertensive rats. Biomed Life Sci 2006;483:321-324.
Tappaz ML. Taurine biosynthetic enzymes and taurine transporter: Molecular identification and regulation. Neurochem Res 2004;29(1):83-96.
Schaffer SW, Ramila KC, Jong CJ, et al. Does taurine prolong lifespan by improving heart function?. Adv Exp Med Biol 2015;803:555- 570.
Xu S, He M, Zhong M, et al. The neuroprotective effects of taurine against nickel by reducing oxidative stress and maintaining mitochondrial function in cortical neurons. Neurosci Lett 2015;590:52-57.
Prentice H, Modi JP, Wu J. Mechanisms of neuronal protection against excitotoxicity, endoplasmic reticulum stress, and mitochondrial dysfunction in stroke and neurodegenerative diseases. Oxid Med Cell Longev 2015;2015:964518.
Lu CL, Tang S, Meng ZJ, et al. Taurine improves the spatial learning and memory ability impaired by sub-chronic manganese exposure. J Biomed Sci 2014;21:51.
Garcia Dopico J, Diaz JP, Alonso TJ, Hernandez TG, Fuentes RC, Diaz MG. Extracellular taurine in the substantia nigra: Taurine-glutamate interaction. J Neurosci Res 2004;76(4):528-538.
Martinez RAE, Vargas RBC, Rodriguez AIC, Perez BGA, Arancibia RS. Antioxidant effects of taurine, vitamin C, and vitamin E on oxidative damage in hippocampus caused by the administration of 3-nitropropionic acid in rats. J Neurosci 2007;114(9):1133-1145.
Lee NY, Kang YS. The brain-to-blood efflux transport of taurine and changes in the blood-brain barrier transport system by tumor necrosis factor-α. Brain Res 2004;1023(1):141-147.
Panatto JP, Jeremias IC, Ferreira GK, et al. Inhibition of mitochondrial respiratory chain in the brain of rats after hepatic failure induced by acetaminophen. Mol Cell Biochem 2011;350(1-2):149- 154.
Sani M, Sebai H, Gadacha W, Boughattas NA, Reinberg A, Ben Attia M. Catalase activity and rhythmic patterns in mouse brain, kidney and liver. Comp Biochem Physiol 2006;145(3-4):331-337.
Ahmad MP, Hussain A, Siddiqui HH, Wahab S, Adak M. Effect of methanolic extract of Asparagus racemosus Willd. on lipopolysaccharide induced-oxidative stress in rats. Pak J Pharm Sci 2015;28(2):509-513.
Anaeigoudari A, Shafei MN, Soukhtanloo M, et al. Lipopolysaccharide-induced memory impairment in rats is preventable using 7-nitroindazole. Arq Neuropsiquiatr 2015;273(9):784-790.
Cherubini A, Ruggiero C, Polidori MC, Mecocci P. Potential markers of oxidative stres in stroke. Free Radic Biol Med 2005;39(7):841- 852.
Casado A, Encarnacion Lopez-Fernandez M, Concepcion Casado M, de La Torre R. Lipid peroxidation and antioxidant enzyme activities in vascular and Alzheimer dementias. Neurochem Res 2007;33(3):450-458.
Anaeigoudari A, Soukhtanloo M, Reisi P, Beheshti F, Hosseini M. Inducible nitric oxide inhibitor aminoguanidine, ameliorates deleterious effects of lipopolysaccharide on memory and long term potentiation in rat. Life Sci 2016;158:22-30.
Czapski GA, Cakala M, Chalimoniuk M, Gajkowska B, Strosznajder B. Role of nitric oxide in the brain during lipopolysaccharideevoked systemic inflammation. J Neurosci Res 2007;85(8):1694- 1703.
Phares TW, Fabis MJ, Brimer CM, Kean RB, Hooper DC. A peroxynitrite-dependent pathway is responsible for blood-brain barrier permeability changes during a central nervous system inflammatory response: TNF-alpha is neither necessary nor sufficient. J Immunol 2007;178(11):7334-7343.
Szabo C, Saunders C, O’Connor M, Salzman AL. Peroxynitrite causes energy depletion and increases permeability via activation of poly (ADP-ribose) synthetase in pulmonary epithelial cells. Am J Respir Cell Mol Biol 1997;16(2):105-109.
Nusetti S, Obregon F, Quintal M, Benzo Z, Lima L. Taurine and zinc modulate outgrowth from goldfish retinal explants. Neurochem Res 2005;30(12):1483-1492.
McMahon GP, Kennedy R, Kelly MT. High performance liquid chromatographic determination of taurine in human plasma using extraction and derivatization. J Pharm Biomed Anal 1996;14(8- 10):1287-1294.
Türközkan N, Seven I, Erdamar H, Çimen B. Effect of vitamin A pretreatment on Escherichia coli-induced lipid peroxidation and level of 3-nitrotyrosine in kidney of guinea pig. Mol Cell Biochem 2005;278(1-2):33-37.
Egan BM, Abdih H, Kelly CJ, Condron C, Bouchier-Hayes DJ. Effect of intravenous taurine on endotoxin-induced acute lung injury in sheep. Eur J Surg 2001;167(8):575-580.
Duffy AJ, Nolan B, Sheth K, Collette H, De M, Bankey PE. Inhibition of alveolar neutrophil immigration in endotoxemia is macrophage in inflammatory protein 2 independent. J Surg Res 2000;90(1):51-57.
El Idrissi A, Trenkner E. Taurine regulates mitochondrial calcium homeostasis. Adv Exp Med Biol 2003;526:527-536.
Schuller-Levis GB, Park E. Taurine and its chloramine: Modulators of immunity. Neurochem Res 2004;29(1):117-126.
Saransaari P, Oja SS. Taurine and neural cell damage. Amino Acids 2000;19(3-4):509-526.
Lallemand F, Witte PD. Taurine concentration in the brain and in the plasma following intraperitoneal injection. Amino Acids 2004;26(2):111-116.
Lourenco R, Camilo ME. Taurine: A conditionally essential amino acid in humans?. Nutr Hosp 2002;17(6):262-270.
Qin L, Wu X, Block ML, et al. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 2007;55(5):453-462.
Kheir-Eldin AA, Motawi TK. Protective effect of vit E, β-carotene and N-acetylcysteine from brain oxidative stress induced in rats by LPS. Int J Biochem 2001;33(5):475-482.
Nolan Y, Vereker E, Lynch Ailen M, Lynch Marina A. Evidence that lipopolysaccharide-induced cell death is mediated by accumulation of reactive oxygen species and activation of p38 in rat cortex and hippocampus. Exp Neurol 2003;184(2):794-804.
Facheris M, Bretta S, Ferrarese C. Peripheral markers of oxidative stres and exitotoxicity in neurodegenerative disorders: Tools for diagnosis and therapy. J Alzheimer’s Dis 2004;6(2):177-184.
Cemeli E, Smith IF, Peers C, et al. Oxygen–induced DNA damage in freshly isolated brain cells compared with cultured astrocytest in the Comet assay. Teratog Carcinog Mutagen 2003;2:43-52.
Khodir AE, Ghoneim HA, Rahim MA, Suddek GM. Montelukast attenuates lipopolysaccharide-induced cardiac injury in rats. Hum Exp Toxicol 2016;35(4):388-397.