Sıçan (Wistar albino) merkezi sinir sisteminde kadmiyum sülfatla (CdSO4) birlikte verilen nitrik oksit sentaz (NOS) inhibitörlerinin toplam lipid ve protein miktarlarına etkisi

Year 2011, Volume: 28 Issue: 4, 175 - 181, 27.01.2012

Mehmet Önger , Hayri Genç , Faruk Tan

https://doi.org/10.5835/jecm.omu.28.04.010

Abstract

Sıçanlarda (Wistar albino) somatomotor kortekse kadmiyum sülfat (CdSO4) verildikten sonra spesifik Nitrik Oksit Sentaz (iNOS) enzim inhibitörü olan Aminoguanidin (AG) ve NO öncüsü olan L-Arjinin (L-Arg)’in beyin ve beyincikteki toplam lipid ve protein miktarlarına etkisini tespit etmek üzere, sunulan çalışma planlandı. Bu amaçla, saf, kontrol, kadmiyum, kadmiyum+L-Arg ve kadmiyum+AG olmak üzere 7’şer sıçandan oluşan 5 grup oluşturuldu. Kadmiyum grubu sıçanlara 0,0021 mg/kg CdSO4 sol hemisfere (bregmanın lateraline) intrakortikal yoldan enjekte edildi. Kontrol grubuna aynı hacimde serum fizyolojik verildi. Kadmiyum+AG grubuna günde iki kez olmak üzere 100 mg/ kg AG 15 gün süreyle intraperitoneal yoldan verildi. Kadmiyum+L-Arjinin grubuna da günde iki kez olmak üzere 1000 mg/kg L-Arjinin 15 gün süreyle intraperitoneal yoldan verildi. Saf grup ise hiçbir işleme tabi tutulmadı ve hiçbir madde verilmedi.
Elde edilen sonuçlar, çalışılan diğer gruplara göre kadmiyumun toplam lipid ve protein miktarlarını düşürdüğünü ve toksik etkiye sahip olduğunu göstermektedir. Ayrıca, sunulan çalışma ile sıçanda kadmiyumun bu nörotoksik etkisinin, spesifik NOS inhibitörü olan AG tarafından azaltıldığına dair sonuçlar yeni bulgulardır. L-Arjininin kadmiyumdan kaynaklanan toplam lipid ve protein miktarlarındaki azalmayı arttırdığını ve bu nörotoksik etkide NO’nun da rol aldığını, elde ettiğimiz bulgular göstermektedir. 

Keywords

Cadmium Sulphate, Cerebrum, Cerebellum, Total Lipid, Total Protein, Aminoguanidine, L-Arginine, Rat

References

• Abdollahi, M., Bahreini-Moghadam, A., Emmami, B., Fooladian, F., Zafariet, K., 2003. Increasing intracellular cAMP and cGMP inhibits cadmium-induced oxidative stress in rat submandibular saliva. Comp. Biochem. Physol. C. 135, 331-336.
• Abdollahi, M., Ranjbar, A., Shadnia, S., Nikfar, S., Rezaie, A., 2004. Pesticides and oxidative stress : a review. Med. Sci. Monit. 10, 141-147.
• Antonio, M.T., Corpas, I., Leret, M.L., 1999. Neurochemical changes in newborn rat’s brain after gestational cadmium and lead exposure. Toxi- cology Letters. 104, 1-9.
• Antonio, M.T., Corredor, L., Leret, M.L., 2003. Study of the activity of several brain enzymes like markers of the neurotoxicity induced by perinatal exposure to lead and/or cadmium. Toxicology Letters. 143, 331-340.
• Bağırıcı, F., Genç, H., Tan, F., Demir, Ş., 2001. Neuroprotective Effect of Nicardipine on Cadmium-Induced Purkinje Cell Death in Rat Cerebel- lum. Neuroscience Research Communications. 29, 2.
• Bruckdorfer, R., 2005. Nitric oxide in physiology and pathology. Molecular Aspects of Medicine. 26, 1-2.
• Brüne, B., Mebmer, U.K., Sandau, K., 1995. The role of nitric oxide in cell injury. Toxicology Letters. 82, 233-237.
• Boje, K.M.K., 1996. Inhibition of nitric oxide synthase attenuates blood-brain barrier disruption during experimental meningitis. Brain Research. 720, 75-83.
• Carageorgiou, H., Tzotzes, V., Patnos, C., Mourouzis, C., Zarros, A., Tsakiris, S., 2004. In vivo and in vitro Effects of Cadmium on Adult Rat Brain Total Antioxidant Status, Acetylcholinesterase, Na+, K+-ATPase and Mg2+-ATPase Activities: Protection by L-Cysteine. Basic&Clinical Pharmacology&Toxicology. 94, 112-118.
• Casalino, E., Sblano, S., Landriscina, C., 1997. Enzyme activity alteration by cadmium administration to rats: the possibility of iron involvement in lipid peroxidation. Archives of Biochemistry and Biophysics. 346, 171-179.
• Chao, C.C., Hu, S., Molitor, T.W., Shaskan, E.G., Peterson, P.K., 1992. Activated microglia mediate neuronal cell injury via a nitric oxide mecha- nism. J. Immunol. 149, 2736-2741.
• Chvapil, M., Elias, S.L., Ryan, J.N., Zukoski, C.F., 1972. Pathophysiology of zinc. In: Pfeiffer CC ed. Neurobiology of Trace Metals Zinc and Copper 2nd ed. Vol 1. New York, Academic Press. 105-124.
• Cochranc, C.G., 1991. Cellular injury by oxidants. Ann. J. Med. 92, 235-305.
• Çakmakçı, M., 1999. Zehirli molekülden haberci maddelerin kraliçeliğine; Nitrik Oksit. Tübitak Bilim ve Teknik Dergisi. 374, 58-62.
• Dawson, D.A., 1994. Nitric oxide and focal cerebral ischemia: multiplicity of actions and diverse outcome. Cerebrovasc Brain Metab. Rev. 6, 299-324.
• Dawson, V.L., Dawson, T.M., London, E.D., Bredt, D.S., Snyder, S.H., 1991. Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc. Natl. Acad. Sci. 88, 6368.
• Dawson, V.L., Dawson, T.M., Bartley, D.A., Uhl, G.R., Snyder, S.H., 1993. Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. J. Neuroscience. 13, 2650-2661.
• Dawson, V.L., 1995. Nitric oxide: role neurotoxicity. Clin. Exp. Pharmacol. Physiol. Australia. 224, 305-308.
• Demir, Ş., Genç, O., Bağırcı, F., Ayyıldız, M., Korkmaz, A., Marangoz, C., 1996. Beyinde çinkonun sebep olduğu hücre ölümüne verapamilin etkisi. O.M.Ü. Tıp Dergisi. 131, 19-25.
• El-Demerdash, F.M., Yousef, M.I, Kedwany, F.S., Baghdadi, H.H. 2004. Cadmium-induced changes in lipid peroxidation, blood hematology, biochemical parameters and semen quality of male rats: protective role of vitamin E and β-carotene. Food and Chemical Tox. 42, 1563- 1571.
• Facchinetti, F., Dawson, V.L., Dawson, T.M. 1998. Free radicals as mediators of neuronal injury. Cell. Mol. Neurobiol. 18, 667-682.
• Genç, H., Bağırıcı, F., Çakır, A., Demir, Ş., Tan, F. 2001. Effect of Flunarize On Cadmium-Induced Purkinje Cell Loss in Rats. Neuroscience Research Communications. 28, 2
• Gross, S.S., Volin, M.S. 1995. Nitric oxide: pathophysiological mechanisms.Ann. Rev. Physiol. 57, 737-769.
• Güven, A., Erginsoy, S., Kaya, N. 2003. Kazlarda karbon tetraklorür zehirlenmesinin biyokimyasal ve patolojik parametrelere etkisi. Kafkas Ü. Vet. Fak. Derg. 9, 131-136.
• Halliwel, B., 1991. Drug antioxidant effects. Drug. 424, 569-605.
• Ino-ue, M., Ohgiya, N., Yamamoto, M. 1998. Effect of aminoguanidine on optic nerve involvement in experimental diabetic rats. Brain Res. 800, 319-322.
• Jhonson, E.M., Chang, J.Y., Kioke, T. Martin, D.P., 1989. Why do neurons die when deprived of trophic factor? Neurobiol. Aging. 10, 549- 552.
• Kaya, S., Pirinççi, İ., Bilgili, A. 1998. Veteriner Hekimliğinde Toksikoloji. Medisan Yayın Serisi.Ankara.35, 222, 232, 273, 276, 355.
• Köse, L. 2005. Sıçan Wistar albino Merkezi Sinir Sisteminde Total Lipid ve Protein Miktarı Üzerine Kadmiyum Sülfatın CdSO4 Etkisi. Yüksek Lisans Tezi.
• Lafuente, A., Fena´ndez-Rey, E., Seara, R., Pe´rez-Lorenzo, M., Esquifino, A.I. 2001. Alternate cadmium exposure differentially affects amino acid metabolism within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats. Neurochemistry International. 39, 187-192.
• Lowry, O.H., Rose Brough, N.J., Farr, A.L., Randall, V.J. 1951. Protein Measurement with the Folin Phenol Reagent. J. Biol. Chem. 193, 265- 275.
• Lu, J., Moochhala, S., Shirhan, M., Chye, K., Teo, A.L., Tan, M.H., Moore, X.L., Wong, M.C., Ling, E.A. 2002. Neuroprotection by amin- oguanidine after lateral fluid-percussive brain injury in rats: a combined magnetic resonance imaging, histopathologic and functional study. Neuropharmacology. 44, 253-263.
• Lynch, D.R., Dawson, T.M. 1994. Secondary mechanism in neuronal trauma. Curr. Opin. Neurol. U.S.A. 76, 510-516.
• Manca, D., Ricard, A.C., Trottier, B., Chevalier, G. 1991. Studies on lipid peroxidation in rat tissues following administration of low and moder- ate doses of cadmium chloride. Toxicology. 67, 303-323.
• Marangoz, C., Genç, H. 1990. Tavşanda intrakortical çinko sülfattan uygulamasından sonra purkinje hücreleri sayısında azalma. T.K.L. Tıp Bil. Araş. Dergisi. 8,67-74.
• Marangoz, C., Ayyıldız, M., Ağar, E. 1994. Evidence that sodium nitroprusside possesses anticonvulsant effects mediated through nitric oxide. Neuro.Report. 5, 2454-2456.
• Marangoz, C. 1996. Nitrik Oksit ve Epilepsi. O.M.Ü. Tıp Dergisi. 133, 165-183.
• Me´ndez-Armenta, M., Villeda-Herna´ndez, J., Barroso-Moguel, R., Nava-Ruı´z, C., Jime´nez-Capdeville, M.E., Rı´os, C. 2003. Brain regional lipid peroxidation and metallothionein levels of developing rats exposed to cadmium and dexamethasone. Toxicology Letters. 144, 151- 157.
• Olson, D.M., Fadamiro, H., Lundgren, J.G., and Heimpel, G.E. 2000. Effects of Sugar Feding on Carbonhydrate and Lipid Metabolism in a Parasitoid Wasp. Physiol. Entomol. 25, 17-26.
• Patrick, L. 2003. Toxic metals and antioxidants. Part II. The rol of antioxidants in arsenic and cadmium toxicity. Altern. Med. Rew. 8, 106-128.
• Poliandri, A.H.B., Velardez, M.O., Cabilla, J.P., Bodo, C.C.A., Machiavelli, L.I., Quinteros, A.F., Duvilanski, B.H. 2004. Nitric Oxide Protects Anterior Pituitary Cells From Cadmium-Induced Apoptosis. Free Radical Biology & Medicine.379, 1463-1471.
• Robb, S.J., Robb-Gaspers, L.D., Scaduto, R.C., Thomas, Jr. A.p., Connor, J.R. 1999. Influence of calcium and iron on cell death and mitochon- drial function in oxidatively stressed astrocytes. J. Neurosci. Res. 556, 674-686.
• Sarkar, S., Yadav, P., Bhatnagar, D. 1997. Cadmium-induced lipid peroxidation and the antioxidant system in rat erythrocytes: the role of anti- oxidants. Journal of Trace Elements in Medicine and Bio. 11, 8-13.
• Satarug, S., Baker, J.R., Reilly, P.E.B., Esumi, H., Moore, M.R. 2000. Evidence for a Synergistic Interaction between Cadmium and Endotoxin Toxicity and for Nitric Oxide and Cadmium Displacement of Metals in the Kidney. NITRIC OXIDE: Biology and Chemistry. 44, 431-440.
• Swarup, D., Naresh, R., Varshney, V.P., Balagangatharathilagar, M., Kumar, P., Nandi, D., Patra, R.C. 2007. Changes in plasma hormones profile and liver function in cows naturally exposed to lead and cadmium around different industrial areas. Research in Veterinary Science. 82, 16- 21.
• Tan, F., Bağırıcı, F., Demir, Ş., Gökçe, F., Genç, H., Marangoz, C. 1999. Kadmiyumun Sıçan Serebellumu Purkinje Hücre Yoğunluğuna Etkisi. O.M.Ü. Tıp Dergisi. 162, 128–132.
• Tan, F. 2003. Sıçan Wistar albino serebellumunda kadmiyumun neden olduğu hücre ölümüne nitrik oksit sentaz NOS inhibitörlerinin etkisi. Doktora Tezi.
• Van Handel, E. 1985. Rapid determination of Total Lipids in Mosquitoes. J. Amer. Mosq. Cont. Assoc. 1, 302-304.
• Van Handel, E. And Day, J.F. 1988. Assay of Lipids, Glycogen and Sugars in Individual Mosquitoes: Correlations with Wing Length in Field- collected Aedes vexans. Journal of the American Mosquito Control Association. 4, 549-550.
• Waisberg, M., Joseph, P., Hale, B., Beyersmann, D. 2003. Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology. 192, 95-117.
• Wu, W., Li, L. 1993. Inhibition of nitric oxide synhase reduces motoneuron death due to spinal root avulsion. Neurscience Letters 153, 121- 124.
• Zhang, Y. M., Liu, X. Z., Lu, H., Mei, L., Liu, Z. P. 2009. Lipit Peroxidation and Ultrastructural Modifications in Brain after Perinatal Exposure to Lead and/or Cadmium in Rat Pups Original Research Article Biomedical and Environmental Sciences. 22, 423-429.