The Protective Effect of Amino-guanidine, an Inducible Nitric Oxide Synthase Inhibitor, on Aluminium Sulphate Neuro-toxicity in the Rat (Wistar albino) Cerebellar Purkinje Cells: Stereological Study

Year 2017, , 7 - 14, 28.12.2017

Burcu Demirel Yılmaz , Hayri Genç , Bengi Baysal Banu Eren

https://doi.org/10.19127/mbsjohs.322015

Cited By: 3

Abstract

Objective: Aluminium
(Al) is quite abundant in nature and humans are frequently exposed to Al in
daily life. Aluminium salts can exist in different forms and they may have
toxic impacts on several tissues including brain. In this study, potential
preventive effects of amino-guanidine (AG) (100 mg/kg, i.p.), an inducible
nitric oxide synthase inhibitor, on neuron damage to be created by aluminium
sulphate (3 mg/kg, i.c.v.) in cerebellar Purkinje cells were determined.

Methods: 24 female
Wistar albino rats were divided into 4 groups with 6 rats in each: Control (C),
Sham (S), Aluminium sulphate (Al₂(SO₄)₃), Aluminium
sulphate + Amino-guanidine (Al₂(SO₄)₃+AG). A
single aluminium sulphate (3 mg/kg) dose dissolved in 0.9% NaCl was injected
intracerebroventricularly to aluminium sulphate and aluminium sulphate +
amino-guanidine groups at the beginning of experiments. Following aluminium
sulphate injection, amino-guanidine (100 mg/kg) dissolved in distilled water was
injected to aluminium sulphate + amino-guanidine group intraperiteonally for 15
days. Nothing was administered to control group, a single dose of 0.9% (3
mg/kg, i.c.v.) sodium chloride (NaCl) was administered to sham group at the
beginning of experiments. Cerebellum tissues of the rats were removed 15 days
after treatments and they were assessed histopathologically and
stereologically.

Results: Stereological
optic fractionation method revealed cerebellar total number of Purkinje cells
as 417615±16238,8 in control group; 378650±20171,6 in Sham group;
272945±15499,5 in Aluminium sulphate group; 324581±16324,8 in Aluminium
sulphate + Amino-guanidine group.

Conclusion: It was
concluded based on present findings that amino-guanidine reduced aluminium
induced Purkinje cell loss through nitric oxide synthase (NOS) inhibition. 

Keywords

Aluminium, Amino-guanidine, Cerebellum, Purkinje cell, Stereology

The Protective Effect of Amino-guanidine, an Inducible Nitric Oxide Synthase Inhibitor, on Aluminium Sulphate Neuro-toxicity in the Rat (Wistar albino) Cerebellar Purkinje Cells: Stereological Study

Abstract

Objective: Aluminium (Al) is quite abundant in nature and humans are frequently exposed to Al in daily life. Aluminium salts can exist in different forms and they may have toxic impacts on several tissues including brain. In this study, potential preventive effects of amino-guanidine (AG) (100 mg/kg, i.p.), an inducible nitric oxide synthase inhibitor, on neuron damage to be created by aluminium sulphate (3 mg/kg, i.c.v.) in cerebellar Purkinje cells were determined.

Methods: 24 female Wistar albino rats were divided into 4 groups with 6 rats in each: Control (C), Sham (S), Aluminium sulphate (Al2(SO4)3), Aluminium sulphate + Amino-guanidine (Al2(SO4)3+AG). A single aluminium sulphate (3 mg/kg) dose dissolved in 0.9% NaCl was injected intracerebroventricularly to aluminium sulphate and aluminium sulphate + amino-guanidine groups at the beginning of experiments. Following aluminium sulphate injection, amino-guanidine (100 mg/kg) dissolved in distilled water was injected to aluminium sulphate + amino-guanidine group intraperiteonally for 15 days. Nothing was administered to control group, a single dose of 0.9% (3 mg/kg, i.c.v.) sodium chloride (NaCl) was administered to sham group at the beginning of experiments. Cerebellum tissues of the rats were removed 15 days after treatments and they were assessed histopathologically and stereologically.

Results: Stereological optic fractionation method revealed cerebellar total number of Purkinje cells as 417615±16238,8 in control group; 378650±20171,6 in Sham group; 272945±15499,5 in Aluminium sulphate group; 324581±16324,8 in Aluminium sulphate + Amino-guanidine group.

Conclusion: It was concluded based on present findings that amino-guanidine reduced aluminium induced Purkinje cell loss through nitric oxide synthase (NOS) inhibition. 

Keywords

Aluminium, Amino-guanidine, Cerebellum, Purkinje cell, Stereology

References

• Aktaç T, Bakar E. The histopathological changes in the mouse thyroid depending on the aluminium. Journal of Cell and Molecular Biology 2002; 1: 69-72.
• 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 Sciences 2016; 158: 22-30.
• Babu E, Gopalakrishnan VK, Sriganth IN, Gopalakrishnan R, Sakthisekaran D. Cisplatin induced nephrotoxicity and the modulating effect of glutathione ester. Mol Cell Biochem 1995; 144:7-11.
• Bharathi, Vasudevaraju P, Govindaraju M, Palanisamy AP, Sambamurti K, Rao KSJ. Molecular Toxicity of Aluminium in Relation to Neurodegeneration. Indian J Med Res 2008; 128:545-556.
• Bondy SC, Liu D, Guo-Ross S. Aluminum treatment induces nitric oxide synthase in the rat brain. Neurochem Int 1998; 33: 51-54.
• Budavari S, O’Neil MJ, Smith A, Heckelman PE. 8th edition. In: Stecher PG. The Merck Index. 1989.
• Buraimoh AA, Tayo I, Ojo SA. Effects of Aluminium Chloride on the Histology of Cerebellum of Wistar Rats. Pharmacology&Toxicology Research 2014; 1:1-4.
• Çabuş N, Oğuz EO, Tufan AÇ, Adıgüzel E. A histological study of toxic effects of aluminium sulfate on rat hippocampus. Biotechnic & Histochemistry 2014; 90-2.
• Çabuş N. The Effect of Aluminium Sulphate on rat Hippocampal Cell Populations at Toxic Dose. Denizli: Pamukkale University Health Sciences Institute, 2012.
• Chaudhary M, Joshi DK, Tripathi S, Kulshrestha S, Mahdi AA. Docosahexaenoic acid ameliorates aluminum induced biochemical and morphological alteration in rat cerebellum. Annals of Neurosciences 2014; 21:1.
• Cheng D, Xi Y, Cao J, Dongdong C, Ma Y, Jiang W. Protective effect of apple (Ralls) polyphenol extract against aluminum-induced cognitive impairment and oxidative damage in rat. NeuroToxicology 2014; 45: 111-120.
• Darbre PD. Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of human breast. Journal of Applied Toxicology 2006; 26: 191-197.
• Eroglu C, Yıldız OG, Saraymen R, Soyuer S, Kılıç S, Özcan S. Aminoguanidine ameliorates radiation-induced oxidative lung damage in rats. Clin Invest Med 2008; 31 (4).
• Esparza JL, Go´mez M, Nogue´s MR, Paternain JL, Mallo J, Domingo JL. 2005. Melatonin reduces oxidative stress and increases gene expression in the cerebral cortex and cerebellum of aluminum-exposed rats. J Pineal Res 2005; 39:129-136.
• Eweka AO, Om’Iniabohs FAE. Histological studies of the effect of the monosodium glutamate on the cerebellum of adult wistar rats. The Internet journal of Neurology 2007; 8: 1-4.
• Flora SJS, Mehta A, Satsangi K, Kannan GM, Gupta M. Aluminum-induced oxidative stress in rat brain: response to combined administration of citric acid and HEDTA. Comparative Biochemistry and Physiology Part 2003; 134(3):319-328.
• Gökçe MF, Kaplan S, Türkkanı A, Kozan R, Ayyıldız M, Emirzeoğlu M, Aslan H, Marangoz C. Nitric oxide synthase inhibitors protect cerebellar Purkinje cells from zinc-induced cell loss in adult rat. Journal of Chemical Neuroanatomy 2011; 41:25-31.
• Gross SS, Volin MS. Nitric oxide: pathophysiological mechanisms. Annu Rev Physiol 1995; 57: 737-769.
• Gundersen HJG, Jensen EB. The efficiency of systematic sampling in stereology and its prediction. J Microsc 1987; 147: 229-263.
• Kamal I, Kamal H. Effects of aluminum on rat cerebellar cortex and the possible protective role of Nigella sativa: a light and electron microscopic study. Egypt J Histol 2013; 36:979-990.
• Korkmaz A, Çiftçi N, Boşnak M, Ağar E. Simplified application of systematic field sampling and low-cost video recording set-up for viewing disector pairs-exemplified in the rat cochlear nucleu. Journal of Microscopy 2000; 200: 26-276.
• Korkmaz A, Kaplan S, Çiftçi N, Bilgiç S, Rağbetli MÇ. A morphometric study of the inferior olivary nucleus in rats treated prenatally with diclofenac sodium. Turkish Journal of Medical Sciences 1996; 26:75-79.
• Korkmaz A, Tümkaya L. Estimation of the section thickness and optical disector height with a simple calibration method. Journal of microscopy 1997; 187:104-109.
• Kozan R, Bostancı MO, Ayas B, Aslan A, Bağırıcı F. Protective Effect of Vitamin E against Iron -induced Neurotoxicity in the Rat Cerebellum. Fırat Tıp Dergisi 2009; 14(1): 07-1.
• Kutlubay R, Oğuz EO, Can B. Vitamin E protection from testicular damage caused by intraperitoneal aluminium. Int J Toxicol 2007 b; 26:297-306.
• Kutlubay R, Oğuz EO, Güven C. Histological and ultrastructural evidence for protective effects on aluminium-Induced kidney damage by intraperitoneal administration of alpha tocopherol. Int J Toxicol 2007a; 26:95-101.
• Lu J, Moochhala S, Shirhan M, Chye K, Teo AL, Tan MH, Moore XL, Wong MC, Ling EA. Neuroprotection by aminoguanidine after lateral fluid-percussive brain injury in rats: a combined magnetic resonance imaging, histopathologic and functional study. Neuropharmacology 2002; 44: 253-263.
• Malekshah AK, Torabizadeh Z, Naghshwar F. Developmental Toxicity of Aluminum from High Doses of AlCl3 in Mice. The Journal of Applied Research 2005; 5 (4): 575-579.
• Marangoz C. Nitric Oxide and Experimental Epilepsy. Ondokuz Mayıs Universty Medical Journal 1996; 13 (3): 165-183.
• Ogasawara Y, Ohata E, Sakamoto T, Ishii K, Takahashi H, Tanabe SA. A Model of aluminium exposure associated with lipid peroxidation in rat brain. Biol Trace Elem Res. Biol Trace Elem Res 2003; 96(1-3): 191-201.
• Oğuz EO, Enli Y, Şahin B, Gönen C, Turgut G. Aluminium sulphate exposure increases oxidative stress and suppresses brain development in Ross broiler chicks. Med Sci Monit 2012; 18(3): 103-108.
• Oğuz EO, Yuksel H, Enli H, Enli Y, Zorbozan O, Can Z, Turgut G. Oxidative and Inflamatory Damage Of Aluminium Suplhate On The Liver Of Term Ross Broiler Chick. Ankara University Medical Journal 2008; 61(1).
• Önger ME, Genç H, Tan F. Effect of NOS inhibitors applied with cadmium sulphate on total lipid and protein quantities in central nervous system of rat (Wistar albino). J Exp Clin Med 2011; 28: 175.
• Özgüneş H, Atasayar S. Aminoguanidine and the its sıgnificance in diseases. Turkiye Klinikleri J Med Sci 2009; 29 (4): 976-86.
• Polat A, Parlakpinar H, Tasdemir S, Colak C, Vardi N, Ucar M. Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats. Acta histochemica 2006; 108:365-71.
• Satarug S, Baker JR, Reilly PEB, Esumi H, Moore MR. 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 2000; 44: 431-440.
• Sefil F, Kozan R, Bostancı MÖ, Bağırıcı F. Protective effect of inhibition of nitric oxide synthase on iron-induced purkinje cell loss. Tıp Araştırmaları Dergisi 2009; 7(2): 71-78.
• Sharma P, Ahmad Shah Z, Kumar A, Islam F, Mishra KP. Role of combined administration of Tiron and glutathione against aluminum-induced oxidative stress in rat brain. J Trace Elem Med Biol 2007; 21(1): 63-70.
• Stevanovıc D, Jovanovıcı MD, Colıc M, Jelenkovıc A, Mıhajlovıc R, Stojanovıc I, Nınkovıc M. The Effect of Aminoguanidine, an İnducible Nitric Oxide Synthase İnhibitör, On AlCl3 Toxicity in the Rat Hippocampus. Arch. Biol Sci 2010; 62 (4): 981-991.
• Tunç AT, Aslan H, Turgut M, Ekici F, Odacı E, Kaplan S. Inhibitory effect of pinealectomy on the development of cerebellar granule cells in the chick: A stereological study 2007; 1138: 214-220.
• Türköz Y, Özerol E. Nitric oxide: actions and pathological roles. Journal of Turgut Özal Medical Center 1997; 4(4): 453-461.
• West MJ, Slomianka L, Gundersen HJ. Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator, Anat Rec 1991; 231: 482-497.
• Yavuz CI, Vaizoğlu AS, Güler Ç. Aluminium in Drinking Water. TAF Prev Med Bull 2013; 12(5): 589-596.
• Yokel AR, Hicks LC, Florence LR. Aluminum Bioavailability From Basic Sodium Aluminum Phosphate, an Approved Food Additive Emulsifying Agent, Incorporated in Cheese. Food Chem Toxicol 2008; 46(6): 2261-6.
• Zatta P, Ibn-Lkayat-Idrissi M, Zambenedetti P, Kilyen M, T. Ki ss (2002): In vivo and in vitro effects of aluminum on the activity of mouse brain acetylcholinestrase. Brain Res 2002; 59: 41-45.