Hürrem Turan AKKOYUN, Aydin Sukru BENGU, Aykut ULUCAN, Mahire BAYRAMOGLU AKKOYUN, Suat EKİN, Yusuf TEMEL, Mehmet ÇİFTÇİ

Kadmiyum ile Oksidatif Strese Maruz Kalan Sıçanların Beyin Dokusunda Astaksantinin Etkisi;Biyokimyasal, Histopatolojik Değerlendirme

Bu çalışmada, ratlarda kadmiyum (Cd), ile meydana gelen beyin hasarını önlemede astaksantinin (AST),koruyucu etkisinin değerlendirilmesi amaçlandı. 32 adet Winstar albino cinsi rat kontol, Kadmiyum (Cd), Astaksantin(AST), Kadmiyum (Cd)+Astaksantin (AST), olmak üzere dört gruba ayrıldı. 30. Günün sonunda rat beyin dokularıalındı. Beyin doku homojenatında malondialdehit (MDA), Glutatyon (GSH) seviyeleri ve süperoksitdismutaz (SOD)enzim aktivitesi ölçülerek, histopatolojik inceleme yapıldı. Beyin dokusu MDA, düzeyleri değerlendirildiğindekontrol grubu ile kıyaslandığında Cd uygulaması yapılan grupta (p<0,01) ve yine Cd+AST uygulanan grupta artış(p<0,05) olduğu belirlendi. Cd uygulaması yapılan gruba oranla Cd+AST grubunda görülen azalmanın istatistikselolarak önemli olduğu belirlenmişdir (p<0,01). GSH düzeyleri değerlendirildiğinde, Cd ve Cd+AST grupları,kontrol grubu ile kıyaslandığında gruplar arasında istatistiksel olarak azalışın olduğu belirlendi (p<0,05). SODenzim aktivitesi değerlendirildiğinde ise Cd ve Cd+AST gruplarında, kontrol grubuna kıyasla görülen azalışın(p<0,01) istatistiksel olarak önemli olduğu, Cd grubuna oranla, Cd+AST uygulaması yapılan grupta SOD düzeyindegörülen artışın önemli olduğu belirlendi (p<0,05). Histopatalojik bulgular değerlendirildiğinde, Serebral korteksve hipokampusta histopatolojik bulgular gruplar arasında farklılık gösterdi. Kontrol ve AST uygulanan gruplardabeyinde normal histolojik yapı gözlenirken, Cd uygulanan grupta ciddi lezyonlar görüldü. Cd+AST grubunda hafifdejeneratif lezyonlar gözlendi. Sonuç olarak, Cd uygulamasına bağlı olarak artan MDA düzeyi, AST uygulması ileazaldı. Cd uygulaması ile azalan GSH düzeyi ve SOD enzim aktivitesi AST uygulaması ile arttı. Aynı zamanda ASTuygulmasının histopatolojik lezyonları azalttığı gözlemlendi. Bundan dolayı, AST’nin Cd kaynaklı beyin oksidatifhasara karşı koruyucu olarak kullanılabileceği düşünülmektedir.

Anahtar Kelimeler:

Astaksantin, Kadmiyum, Oksidatif stres

Effect Of Astaxanthin On Rat Brains Against Oxidative Stress Induced By Cadmium:Biochemical, Histopathological Evaluation

Aim of this study is to evaluate protective impact of Astaxanthin (AST) on rats with experimentalbrain injury induced with Cadmium (Cd). 32 male Wistar albino rats were divided into four groups as Control,Cadmium, Astaxanthin (AST), Cadmium (Cd)+Astaxanthin (AST). Rat brain tissues were obtained at the endof 30th day. Malondialdehyde (MDA), glutathione (GSH) levels and superoxide dismutase (SOD) enzymeactivities were measured in brain homogenates and histopathological examination was performed. MDA levelswere improvement in cadmium administered group (p<0.01) as well as Cd+AST administered group (p<0.05)compared to control group. In addition a substantial reduction Cd+AST group was observed compared to cadmiumadministered group (p<0.01). GSH level shows a decrease in Cd and Cd+AST groups compared to control (p<0.05).SOD enzyme activity was found significantly lower in Cd and Cd+AST groups compared to control (p<0.01). Inaddition, increase of SOD in Cd+AST group compared to cadmium group was also found significant (p<0.05).Histopathological findings in the cerebral cortex and hippocampus were different between groups. In the controland AST administered groups, normal histological structure was observed in the brain, while severe lesions wereseen in the Cd administered group and in the Cd+AST group only mild degenerative lesions were observed.As a result, elevated MDA level due to Cd administration was attenuated with AST administration. Decreased GSHlevel and SOD enzyme activity due to Cd administration was increased with AST administration. In addition, ASTadministration decreased histopathological lesions. Consequently, it is thought that AST may be used for protectionagainst brain oxidative damage due to Cd.

Keywords:

Astaxanthin, cadmium, oxidative stress,

PDF

___

Adefegha SA, Omojokun OS, Oboh G, Fasakin O, Ogunsuyi O, 2016. Modulatory effects of ferulic acid on cadmium-induced brain damage. Journal of evidence-based complementary & alternative medicine, 21: 56-61.
Alaee S, Talaiekhozani A, Rezaei S , Alaee K , Yousefian E, 2014. Cadmium and male infertility. Journal of Infertility and Reproductive Biology, 2:62-69.
Amara S, Douki T, Garrel C, Favier A, Ben Rhouma K, Sakly M, Abdelmelek H, 2011. Effects of static magnetic field and cadmium on oxidative stress and DNA damage in rat cortex brain and hippocampus. Toxicology and industrial health, 27: 99-106.
Anderson G, Bancroft J, 2002. Tissue processing and microtomy, In: Bancroft, John, Gamble, Marilyn (Eds.), Theory and Practice of Histological Techniques. 5th edition, Harcourt Publishers Limited, London: Churchill Livingstone.
Chan KC, Mong MC, Yin MC, 2009. Antioxidative and Anti‐Inflammatory Neuroprotective Effects of Astaxanthin and Canthaxanthin in Nerve Growth Factor Differentiated PC12 Cells. Journal of food science,74: 225-231.
Chen S, Ren Q, Zhang J, Ye Y, Zhang Z, Xu Y, Gao W, 2014. N‐acetyl‐L‐cysteine protects against cadmium‐induced neuronal apoptosis by inhibiting ROS‐dependent activation of Akt/mTOR pathway in mouse brain. Neuropathology and applied neurobiology, 40: 759-777.
Choi HD, Kang HE, Yang SH, Lee MG, Shin WG, 2011. Pharmacokinetics and first-pass metabolism of astaxanthin in rats. British Journal of Nutrition,105: 220-227.
Ciesielski T, Weuve J, Bellinger DC, Schwartz J, Lanphear B, Wright RO, 2012. Cadmium exposure and neurodevelopmental outcomes in US children. Environmental health perspectives,120: 758.
Çetin C, Kose AA, Aral E, 2001. Protective effect of fucoidin (a neutrophil rolling inhibitor) on ischemia reperfusion injury: experimental study in rat epigastric island flaps. Ann Plast Surg, 47: 540
El‐Missiry MA, Shalaby F, 2000. Role of β‐carotene in ameliorating the cadmium‐induced oxidative stress in rat brain and testis. Journal of biochemical and molecular toxicology,14: 238-243.
Evans PH, 1993. Free radicals in brain metabolism and pathology. British Medical Bulletin, 49: 577-587.
Fairbans VF, Klee GG, 2016. Biochemical aspects of hematology. İn: CoA.Burtis and E.R.Ashwood, Editors, Tietz Textbook of clinical Chemistry,Sounders, Philadelphia, 1999: 1991-2106.
Fowler BA, 2009. Monitoring of human populations for early markers of cadmium toxicity: a review. Toxicology and applied pharmacology, 238: 294-300.
Gabbiani G, Baic D, Deziel C, 1967. Toxicity of cadmium for the central nervous system. Experimental neurology,18: 154-160.
Gonçalves JF, Fiorenza AM, Spanevello RM, Mazzanti CM, Bochi GV, Antes FG, Schetinger MRC, 2010. N-acetylcysteine prevents memory deficits, the decrease in acetylcholinesterase activity and oxidative stress in rats exposed to cadmium. Chemico-biological interactions, 186: 53-604.
Górka IM, Januszewska L, Michalak A, Prokopowicz A , Januszewska E , Pawlas N , Pawlas K, 2015. Effects of chronic exposure to lead, cadmium, and manganese mixtures on oxidative stress in rat liver and heart. Arh Hig Rada Toksikol, 66: 51-62
Gurlek A, Celik M, Parlakpinar H, 2006. The protective effect of melatonin on ischemia-reperfusion injury in the groin (inferior epigastric) flap model in rats. J Pineal Res, 40: 312 Hart RP, Rose CS, Hamer R.M, 1989. Neuropsychological effects of occupational exposure to cadmium. Journal of clinical and experimental neuropsychology, 11: 933-943.
Higuera-Ciapara I, Felix-Valenzuela L, Goycoolea FM, 2006. Astaxanthin: a review of its chemistry and applications. Critical reviews in food science and nutrition, 46: 185-196.
Hwang YH, Hong SG, Mun SK, Kim SJ, Lee SJ, Kim JJ, Yee ST, 2017. The Protective Effects of Astaxanthin on the OVA-Induced Asthma Mice Model. Molecules, 22, 2019.
Ikeda Y, Tsuji S, Satoh A, Ishikura M, Shirasawa T, Shimizu T, 2008. Protective effects of astaxanthin on 6‐hydroxydopamine‐induced apoptosis in human neuroblastoma SH‐SY5Y cells. Journal of neurochemistry, 107: 1730-1740.
Karoui-Kharrat D, Kaddour H, Hamdi Y, Mokni M, Amri M, Mezghani S, 2017. Response of antioxidant enzymes to cadmium-induced cytotoxicity in rat cerebellar granule neurons. Open Life Sciences, 12: 113-119.
Lilli RD, 2008. The Hematoxylin and Eosin, In: Gamble, Marilyn, Histopathologic Technique and Practical Biochemistry. 8th edition, Elsevier Limited, London: Churchil Livingstone.
Liu X, Shibata T, Hisaka S, Osawa T, 2009. Astaxanthin inhibits reactive oxygen species-mediated cellular toxicity in dopaminergic SH-SY5Y cells via mitochondria-targeted protective mechanism. Brain research, 1254: 18-27.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ, 1951. Protein Measurement With the Folin Phenol Reagent. The Journal of Biological Chemistry, 265-275.
Mendez-Armenta M, Barroso-Moguel R, Villeda-Hernández J, Nava-Ruız C, Rıos C, 2001. Histopathological alterations in the brain regions of rats after perinatal combined treatment with cadmium and dexamethasone. Toxicology,161: 189-199.
Méndez-Armenta M, Ríos C, 2007. Cadmium neurotoxicity. Environmental Toxicology and Pharmacology, 23: 350-358.
Nemmiche S, Chabane-Sari D, Guiraud P, 2007. Role of α-tocopherol in cadmium-induced oxidative stress in Wistar rat's blood, liver and brain. Chemico-biological interactions, 170: 221-230.
Ohkawa H, Ohishi N, Yagı K, 1979. Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction. Analytical Biochemistry, 95: 351-358.
Otton R, Marin DP, Bolin AP, Santos, RD, Polotow TG, Sampaio SC, Barros MP, 2010. Astaxanthin ameliorates the redox imbalance in lymphocytes of experimental diabetic rats. Chemico-biological interaction, 186: 306-315.
Provias JP, Ackerley CA, Smith C, Becker LE, 1994. Cadmium encephalopathy: a report with elemental analysis and pathological findings. Acta neuropathologica, 88: 583-586.
Satarug S, Garrett SH, Sens MA, Sens DA, 2010. Cadmium environmental exposure and health outcomes. Environ Health Perspect, 118: 182-190.
Seyhan N, Canseven AG, 2006. In vivo effects of ELF MFs on collagen synthesis, free radical processes, natural antioxidant system, respiratory burst system, immune system activities, and electrolytes in the skin, plasma, spleen, lung, kidney, and brain tissues. Electromagn Biol. Med 25: 291-305
Shagirtha K, Bashir N, Milton Prabu S, 2016. Neuroprotective efficacy of hesperetin against cadmium induced oxidative stress in the brain of rats. Toxicology and industrial health, 33: 454-468.
Shagirtha K, Muthumani M, Prabu SM, 2011. Melatonin abrogates cadmium induced oxidative stress related neurotoxicity in rats. Eur Rev Med Pharmacol Sci, 15: 1039-1050.
Shen H, Kuo CC, Chou J, Delvolve A, Jackson SN, Post, J, Harvey BK, 2009. Astaxanthin reduces ischemic brain injury in adult rats. The FASEB, 23: 1958-1968.
Singh N, Rani P, Gupta M, Goel N ,Tandan N, 2013. Effects of aqueous extract of Camellia sinensis (l.) O. kuntze on liver markers of cadmium treated rats. Journal of Biotechnology and Pharmaceutical Research, 4: 89-93.
Shukla GS, Chandra SV, 1987. Concurrent exposure to lead, manganese, and cadmium and their distribution to various brain regions, liver, kidney, and testis of growing rats. Archives of environmental contamination and toxicology, 16: 303-310.
Stoeppler M, 1991. Cadmium. In: Merian, E. (Ed.), Metals and their Compounds in the Environment. VCH, Weinheim, NewYork, Basel, Cambridge.
Stohs SJ, Bagchi D, Hassoun E, Bagchi M, 2001. Oxidative mechanisms in the toxicity of chromium and cadmium ions. Journal Environ.Pathol.Toxicol.Oncol, 20: 77-88.
Sun Yi, Oberley LW, Ying Li, 1988. A simple method for clinical assay of superoxide dismutase. Clinical Chemistry, 3413: 497-500.
Suzer T, Coskun E, Demir S, 2000. Lipid peroxidation and glutathione levels after cortical injection of ferric chloride in rats: effect of trimetazidine and deferoxamine. Res. Exp. Med, 199: 223-229
Szkup-Jablonska M, Karakiewicz B, Grochans E, Jurczak A, Nowak-Staz G, Rotter I, Prokopowicz A, 2012. Effects of blood lead and cadmium levels on the functioning of children with behaviour disorders in the family environment. Annals of Agricultural and Environmental Medicine, 19: 241-246.
Xia E, Rao G, Remmen HV, Heydari A, Richardson A, 1994. Activites of Antioxidant Enzymes in Various Tissues of Male Fischer 344 Rats Are Altered by Food Restriction. Biochemical and Molecular Roles of Nutrients, 125: 195-201.
Tietz F, 1969. Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues. Analytical Biochemistry, 27: 502-522.
Wong KL, Klaassen CD, 1982. Neurotoxic effects of cadmium in young rats. Toxicology and applied pharmacology, 63: 330-337. Wu S, Li S, Xu XR, Deng GF, Li F, Zhou J, Li HB, 2012. Sources and bioactivities of astaxanthin. Int. J. Mod. Biol. Med, 1: 96-107. Yadav R, Archana J, Goyal PK, 2010. Protective action of diltiazem against cadmium induced biochemical changes in the brain of Swiss albino mice. Annals of neurosciences, 12: 37-40.
Yamagishi R, Aihara M, 2014. Neuroprotective effect of astaxanthin against rat retinal ganglion cell death under various stresses that induce apoptosis and necrosis. Molecular vision, 20: 1796.
Yoshida S, 2001. Re-evaluation of acute neurotoxic effects of Cd 2+ on mesencephalic trigeminal neurons of the adult rat. Brain research, 892: 102-110.
Zhang XS, Zhang X, Zhou ML, Zhou XM, Li N, Li W, Shi JX, 2014. Amelioration of oxidative stress and protection against early brain injury by astaxanthin after experimental subarachnoid hemorrhage. Journal of neurosurgery, 121: 42-54. Zuluaga M, Barzegari A, Letourneur D, Gueguen V, Pavon-Djavid G, 2017. Oxidative Stress Regulation on Endothelial Cells by Hydrophilic Astaxanthin Complex: Chemical, Biological, and Molecular Antioxidant Activity Evaluation. Oxidative Medicine and Cellular Longevity, Article ID 8073798.