The Protective Effect of Nicardipine on Iron-Induced Purkinje Cell Loss in Rat Cerebellum: A Stereological Study

Year 2008, Volume: 13 Issue: 3, 167 - 170, 01.06.2008

Ramazan Kozan M. Ömer Bostancı Fatih Sefil Faruk Bağırıcı

Abstract

Objective: The aim of the present study is to investigate the effect of nicardipine, a calcium channel blocker, on the neurotoxicity induced by intracerebroventricular (i.c.v.) iron injection in rats. Materials and Methods: Animals were divided into three groups; control, iron and iron+nicardipine groups. Rats in iron and iron+nicardipine groups received i.c.v. FeCl3, while rats in control group received the same volume of saline. All animals were kept alive for ten days following the operation and animals in iron+nicardipine group were injected intraperitoneally nicardipine (10 mg/kg/day) once a day during this period. After ten days, all rats were perfused intracardially and cerebellar tissues were stained with Cresyl violet. Means of total Purkinje cells numbers in the cerebellum were estimated using the optical fractionator counting method. Results: Means of total Purkinje cells numbers in the cerebellum as follows: 317182±9667, 209002±7836 and 265659±8291 in the control, iron and iron+nicardipine groups, respectively. Total number of Purkinje cells in iron and iron+nicardipine groups were significantly lower than control animals (p< 0.05). However, comparison between iron and iron+nicardipine groups revealed that nicardipine significantly attenuates the iron-induced Purkinje cell loss (p

Keywords

-

Sıçan Serebellumunda Demirin İndüklediği Purkinje Hücre Kaybına Nikardipinin Koruyucu Etkisi: Stereolojik Bir Çalışma

Abstract

Amaç: Bu çalışmanın amacı, sıçanlarda, intraserebroventriküler (i.c.v.) olarak injekte edilen demirin indüklediği nörotoksisite üzerine bir kalsiyum kanal blokörü olan nikardipinin etkisini incelemektir. Gereç ve Yöntem: Hayvanlar kontrol, demir ve demir+nikardipin olmak üzere üç gruba ayrıldı. Demir ve demir+nikardipin grubuna i.c.v. olarak FeCl3, kontrol grubuna ise aynı hacimde salin verildi. Bütün hayvanlar operasyonu takiben on gün yaşatılırken bu esnada demir+nikardipin grubuna 10 mg/kg/gün dozunda nikardipin intraperitoneal olarak verildi. Onuncu günde, sıçanların tamamı intrakardiyak olarak perfüze edildi ve serebellum dokuları kresil violet ile boyandı. Serebellumda ortalama toplam Purkinje hücre sayıları optik parçalama sayım metodu kullanılarak hesaplandı. Bulgular: Hücre sayıları kontrol, demir ve demir+nikardipin gruplarında sırasıyla 317182±9667, 209002±7836 ve 265659±8291 olarak bulundu. Total Purkinje hücresi sayısı, demir ve demir+nikardipin gruplarında kontrol grubuna göre anlamlı olarak daha azdı (p

Keywords

Demir, hücre ölümü, Purkinje hücresi, nikardipin, stereoloji

References

• Aisen P, Enns C, Wessling-Resnick M. Chemistry and biology of eukaryotic iron metabolism. Int J Biochem Cell Biol 2001; 33: 940-959.
• Ponka P. Hereditary causes of disturbed iron homeostasis in the central nervous system. Ann N Y Acad Sci 2004; 1012: 267-281.
• Willmore LJ, Hiramatsu M, Kochi H, Mori A. Formation of superoxide radicals after FeCl3 injection into rat isocortex. Brain Res 1983; 277: 393-396.
• Porter NA, Caldwell SE, Mills KA. Mechanisms of free radical oxidation of unsaturated lipids. Lipids 1995; 30: 277-290.
• Robb SJ, Robb-Gaspers LD, Scaduto RC, Jr. Thomas AP, Connor JR. Influence of calcium and iron on cell death and mitochondrial function in oxidatively stressed astrocytes. J Neurosci Res 1999; 55: 674-686.
• Orrenius S, Ankarcrona M, Nicotera P. Mechanism of calcium related cell death. Adv Neurol 1996; 71: 137-151.
• Gaasch JA, Geldenhuys WJ, Lockman PR, Allen DD, Van der Schyf CJ. Voltage-gated calcium channels provide an alternate route for iron uptake in neuronal cell cultures. Neurochem Res 2007; 32:1686-1693.
• Shiino A, Matsuda M, Handa J, Marikawa S. Calcium antagonist and, acute brain ischemia. Effects of nilvadipine and nicardipine on middle cerebral artery occlusion in rats. Nippon Geka Hokan 1991; 60: 38- 44.
• Kucharczyk J, Chew W, Derugin N, et al. Nicardipine reduces ischemic brain injury, magnetic resonance imaging/spectroscopy study in cats. Stroke 1989; 20: 268-274.
• Bonthius DJ, Bonthius NE, Napper RM, et al. Purkinje cell deficits in nonhuman primates following weekly exposure to ethanol during gestation. Teratology 1996; 53: 230–236.
• Chen WJ, Edwards RB, RomeroRD, Parnell SE, Monk RJ. Long- term nicotine exposure reduces Purkinje cell number in the adult rat cerebellar vermis. Neurotoxicol and Teratol 2003; 3: 329-334.
• Bagirici F, Genç H, Tan F, Demir Ş. Neuroprotective effect of nicardipine on cadmium-induced Purkinje cell death in rat cerebellum. Neurosci Res Commun 2001; 29: 99-105
• Bostanci MO, Bagirici F, Canan S. A calcium channel blocker flunarizine attenuates the neurotoxic effects of iron. Cell Biol Toxicol 2006; 22: 119-125.
• Gundersen HJ. Stereology of arbitrary particles. A review of unbiased number and size estimator and the presentation of some new ones, in memory of William R Thompson. J Microsc 1986; 143: 3-45.
• Gundersen HJ, Bendtsen TF, Korbo L, et al. A some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS 1988; 96: 379-394.
• Pauli J, Wilce P, Bedi KS. Acute exposure to alcohol during early postnatal life causes a deficit in the total number of cerebellar Purkinje cells in the rat. J Comp Neurol 1995; 360: 506–512.
• Welsh JP, Yuen G, Placantonakis DG, et al. Why do Purkinje cells die so easily after global brain ischemia? Aldolase C EAAT4, and the cerebellar contribution to posthypoxic myoclonus. Adv Neurol 2002; 89:331-359.
• Halliwell B, Gutteridge JMC. Iron as biological pro-oxidant. ISI Atlas Sci Biochem 1988; 1: 48–52.
• Uematsu D, Araki N, Greenberg JH. Alterations in cytosolic free calcium in the cat cortex during bicuculline-induced epilepsy. Brain Res Bull 1990; 24: 285-288
• Sorkin EM, Clissold SP. Nicardipine: a review of its pharmacodynamic therapeutic efficacy, in the treatment of angina pectoris, hypertension and related cardiovascular disorders. Drugs 1987; 33: 296-345. properties, and
• Flamm ES, Adams HP Jr, Beck DW, et al. Dose-escalation study of intravenous nicardipine in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 1988; 68: 393–400.
• Bagirici F, Gokce FM, Marangoz C. Depressive effect of nicardipine on penicillin-induced epileptiform activity in rats. Neurosci Res Commun 1999; 24:149-154.
• Kabul Tarihi:25.05.2008