The influence of melatonin supplementation against aluminum-induced toxicity in brains of male rats

The influence of melatonin supplementation against aluminum-induced toxicity in brains of male rats

Aluminum (Al), an ubiquitous element in nature, enters the body primarily through gastrointestinal tract, respiratory system and skin. Being a powerful neurotoxin for human brain, Al was reported to be involved in the etiology of Alzheimer's disease due to its easy access and accumulation in the central nervous system. Melatonin (Mel) is a tryptophan-derived neurohormone in animals and plants, and produced in the pineal gland of all mammalian species. The present study examines the effects of Mel on Al-induced oxidative stress, inflammation, tissue factor production and brain damage in rat brain. Wistar albino rats were divided into four groups. Group I: control animals; Group II: rats injected with 10 mg/kg Mel; Group III: rats injected with 5 mg/kg Al2(SO4)3; and Group IV: rats injected combination of Al and Mel (5 mg/kg Al2(SO4)3 and 10 mg/kg Mel). Animals were injected three times a week for one month. At the end of the month, rats were sacrificed, their brains were removed. It was found that lipid peroxidation, protein carbonyl, advanced oxidation protein products, hydroxyproline levels, tissue factor, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, myeloperoxidase, acetylcholine esterase, alkaline phosphatase, acid phosphatase and glucose-6-phosphate dehydrogenase activities were increased, while paraoxonase, arylesterase, sodium potassium ATPase activities and glutathione levels were decreased in the Al-treated group. Mel treatment reversed these changes by demonstrating significant antioxidant effects. Results indicated that Mel has potential therapeutic value against Al-induced oxidative stress in the rat brain tissue and these effects may be related to its antioxidant activities.

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  • Nelson N. Metal ion transporters and homeostasis. EMBO J. 1999; 18(16): 4361-4371. [CrossRef]
  • Verstraeten SV, Aimo L, Oteiza PI. Aluminium and lead: molecular mechanisms of brain toxicity. Arch Toxicol. 2008; 82(11): 789-802.
  • Bhattacharjee S, Zhao Y, Hill JM, Culicchia F, Kruck TP, Percy ME, Pogue AI, Walton JR, Lukiw WJ. Selective accumulation of aluminum in cerebral arteries in Alzheimer's disease (AD). J Inorg Biochem. 2013; 126: 35-37. [CrossRef]
  • Fulgenzi A, Vietti D, Ferrero ME. Aluminium involvement in neurotoxicity. BioMed Res Int. 2014; 2014. [CrossRef]
  • Zatta P, Ibn-Lkhayat-Idrissi M, Zambenedetti P, Kilyen M, Kiss T. In vivo and in vitro effects of aluminum on the activity of mouse brain acetylcholinesterase. Brain Res Bull. 2002; 59(1): 41-45. [CrossRef]
  • Reinke CM, Breitkreutz J, Leuenberger H. Aluminium in over-the-counter drugs: risks outweigh benefits? Drug Saf. 2003; 26(14): 1011-1025.
  • Şahin G, Varol I, Temizer A, Benli K, Demirdamar R, Duru S. Determination of aluminum levels in the kidney, liver, and brain of mice treated with aluminum hydroxide. Biol Trace Elem Res. 1994; 41(1-2): 129-135.
  • Sushma NJ, Rao KJ. Total ATPases activity in different tissues of albino mice exposed to aluminium acetate. J Environ Biol. 2007; 28(2 Suppl): 483-484.
  • Krewski D, Yokel RA, Nieboer E, Borchelt D, Cohen J, Harry J, Kacew S, Lindsay J, Mahfouz AM, Rondeau V. Human health risk assessment for aluminium, aluminium oxide, and aluminium hydroxide. J Toxicol Environ B. 2007; 10(1): 1-269.
  • Makala LH. The role of indoleamine 2, 3 dioxygenase in regulating host immunity to leishmania infection. J Biomed Sci. 2012; 19(5): 1-8.
  • Yuan CY, Lee YJ, Hsu GSW. Aluminum overload increases oxidative stress in four functional brain areas of neonatal rats. J Biomed Sci. 2012; 19: 51.
  • Yu L, Jiang R, Su Q, Yu H, Yang J. Hippocampal neuronal metal ion imbalance related oxidative stress in a rat model of chronic aluminum exposure and neuroprotection of meloxicam. Behav Brain Funct. 2014; 10(6): 1-10.
  • Abdel Moneim AE, Ortiz F, Leonardo-Mendonca RC, Vergano-Villodres R, Guerrero-Martínez JA, López LC, AcuñaCastroviejo D, Escames G. Protective effects of melatonin against oxidative damage induced by Egyptian cobra (Naja haje) crude venom in rats. Acta Trop. 2015; 143: 58-65. [CrossRef]
  • Reiter JR, Tan DX, Rosales-Corral S, C. Manchester L. The universal nature, unequal distribution and antioxidant functions of melatonin and its derivatives. Mini Rev Med Chem. 2013; 13(3): 373-384.
  • Rodriguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ. Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res. 2004; 36(1): 1-9.
  • Reiter RJ, Tan DX, Osuna C, Gitto E. Actions of melatonin in the reduction of oxidative stress. J Biomed Sci. 2000; 7(6): 444-458.
  • Nazıroğlu M. Role of selenium on calcium signaling and oxidative stress-induced molecular pathways in epilepsy. Neurochem Res. 2009; 34(12): 2181-2191. Nazıroğlu M, Kutluhan S, Uğuz AC, Çelik Ö, Bal R, Butterworth PJ. Topiramate and vitamin E modulate the electroencephalographic records, brain microsomal and blood antioxidant redox system in pentylentetrazol-induced seizure of rats. J Membr Biol. 2009; 229(3): 131-140.
  • Wang W, Ballatori N. Endogenous glutathione conjugates: occurrence and biological functions. Pharmacol Rev. 1998; 50(3): 335-356.
  • Praticò D, Uryu K, Sung S, Tang S, Trojanowski JQ, Lee VM. Aluminum modulates brain amyloidosis through oxidative stress in APP transgenic mice. FASEB J. 2002; 16(9): 1138-1140.
  • Butterfield DA, Lauderback CM. Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid β-peptide-associated free radical oxidative stress 1, 2. Free Radic Biol Med. 2002; 32(11): 1050-1060. [CrossRef]
  • Stadtman ER. Protein oxidation and aging. Science. 1992; 257(5074): 1220-1224. [CrossRef]
  • Evans P, Lyras L, Halliwell B. Measurement of protein carbonyls in human brain tissue. Methods Enzymol. 1999; 300: 145-156. [CrossRef]
  • Al-Amin MM, Reza HM, Saadi HM, Mahmud W, Ibrahim AA, Alam MM, Alam MM, Kabir N, Saifullah ARM, Tropa ST, Quddus AHRM. Astaxanthin ameliorates aluminum chloride-induced spatial memory impairment and neuronal oxidative stress in mice. Eur J Pharmacol. 2016; 777: 60-69. [CrossRef]
  • Sharma DR, Wani WY, Sunkaria A, Kandimalla RJ, Verma D, Cameotra SS, Gill KD. Quercetin protects against chronic aluminum-induced oxidative stress and ensuing biochemical, cholinergic, and neurobehavioral impairments in rats. Neurotox Res. 2013; 23(4): 336-357.
  • Emekli‐Alturfan E, Kasikci E, Yarat A. Tissue factor activities of streptozotocin induced diabetic rat tissues and the effect of peanut consumption. Diabetes Metab Res Rev. 2007; 23(8): 653-658.
  • Mackman N. Role of tissue factor in hemostasis, thrombosis, and vascular development. Arterioscler Thromb Vasc Biol. 2004; 24(6): 1015-1022.
  • Ingram G, Hills M. Reference method for the one-stage prothrombin time test on human blood. International committee for standardization in hematology. Thromb Haemost 1976; 36(1): 237-238.
  • García J, Reiter R, Pié J, Ortiz G, Cabrera J, Sáinz R, Acuña-Castroviejo D. Role of pinoline and melatonin in stabilizing hepatic microsomal membranes against oxidative stress. J Bioenerg Biomembr. 1999; 31(6): 609-616.
  • Benzi G, Marzatico F, Pastoris O, Villa R. Relationship between aging, drug treatment and the cerebral enzymatic antioxidant system. Exp Gerontol. 1989; 24(2): 137-148.
  • Reddy PH. Amyloid precursor protein‐mediated free radicals and oxidative damage: Implications for the development and progression of Alzheimer's disease. J Neurochem. 2006; 96(1): 1-13.
  • Gómez M, Esparza JL, Nogués MR, Giralt M, Cabré M, Domingo JL. Pro-oxidant activity of aluminum in the rat hippocampus: gene expression of antioxidant enzymes after melatonin administration. Free Radic Biol Med. 2005; 38(1): 104-111.
  • Frank-Cannon TC, Alto LT, McAlpine FE, Tansey MG. Does neuroinflammation fan the flame in neurodegenerative diseases? Mol Neurodegener. 2009; 4(1): 47.
  • Nehru B, Bhalla P, Garg A. Further evidence of centrophenoxine mediated protection in aluminium exposed rats by biochemical and light microscopy analysis. Food Chem Toxicol. 2007; 45(12): 2499-505. [CrossRef]
  • Bulan NÖ, Sarıkaya-Ünal G, Tunalı S, Arda-Pirinççi P, Yanardağ R. Melatonin is a potent modulator of antioxidative defense and cellular proliferation against aluminum toxicity in rats. Turk J Biol. 2015; 39(6): 911-924. [CrossRef]
  • Kaur P, Sodhi R. Memory recuperative potential of rifampicin in aluminum chloride-induced dementia: Role of pregnane x receptors. Neuroscience. 2015; 288: 24-36. [CrossRef]
  • Moumen R, Ait-Oukhatar N, Bureau F, Fleury C, Bouglé D, Arhan P, Neuville D, Viader F. Aluminium increases xanthine oxidase activity and disturbs antioxidant status in the rat. J Trace Elem Med Biol. 2001; 15(2): 89-93. [CrossRef]
  • Teixeira A, Morfim MP, Cordova CA, Charão CC, Lima VR, Creczynski‐Pasa TB. Melatonin protects against prooxidant enzymes and reduces lipid peroxidation in distinct membranes induced by the hydroxyl and ascorbyl radicals and by peroxynitrite. J Pineal Res. 2003; 35(4): 262-268.
  • Abdel-Salam OM, Khadrawy YA, Mohammed NA. Neuroprotective effect of nitric oxide donor isosorbide-dinitrate against oxidative stress induced by ethidium bromide in rat brain. EXCLI J. 2012; 11: 125-141.
  • Menini T, Gugliucci A. Paraoxonase 1 in neurological disorders. Redox Rep. 2014; 19(2): 49-58.
  • Rajkovic MG, Rumora L, Barisic K. The Paraoxonase 1, 2 and 3 in humans. Biochem Med. 2011; 21(2): 122-130.
  • Hernández AF, Gil F, Leno E, López O, Rodrigo L, Pla A. Interaction between human serum esterases and environmental metal compounds. Neurotoxicology. 2009; 30(4): 628-635. [CrossRef]
  • Grisaru D, Sternfeld M, Eldor A, Glick D, Soreq H. Structural roles of acetylcholinesterase variants in biology and pathology. Eur J Biochem. 1999; 264(3): 672-686.
  • Kumar A, Dogra S, Prakash A. Protective effect of curcumin (Curcuma longa), against aluminium toxicity: Possible behavioral and biochemical alterations in rats. Behav Brain Res. 2009; 205(2): 384-390. [CrossRef]
  • Kumar A, Prakash A, Dogra S. Neuroprotective effect of carvedilol against aluminium induced toxicity: possible behavioral and biochemical alterations in rats. Pharmacol Rep. 2011; 63(4): 915-923. [CrossRef]
  • Ravi S, Prabhu B, Raju T, Bindu P. Long-term effects of postnatal aluminium exposure on acetylcholinesterase activity and biogenic amine neurotransmitters in rat brain. Indian J Physiol Pharmacol. 2000; 44(4): 473-478.
  • Rodrigo R, Rivera G, Orellana M, Araya J, Bosco C. Rat kidney antioxidant response to long-term exposure to flavonol rich red wine. Life Sci. 2002; 71(24): 2881-2895. [CrossRef]
  • Silva VS, Duarte AI, Rego AC, Oliveira CR, Gonçalves PP. Effect of chronic exposure to aluminium on isoform expression and activity of rat (Na+/K+) ATPase. Toxicol Sci. 2005; 88(2): 485-494. [CrossRef]
  • Sumathi T, Shobana C, Thangarajeswari M, Usha R. Protective effect of L-Theanine against aluminium induced neurotoxicity in cerebral cortex, hippocampus and cerebellum of rat brain–histopathological, and biochemical approach. Drug Chem Toxicol. 2015; 38(1): 22-31.
  • Yu SP. Na+, K+-ATPase: The new face of an old player in pathogenesis and apoptotic/hybrid cell death. Biochem Pharmacol. 2003; 66(8): 1601-1609. [CrossRef]
  • Millán JL. Alkaline phosphatases: Structure, substrate specificity and functional relatedness to other members of a large superfamily of enzymes. Purinergic Signal. 2006; 2(2): 335-341.
  • Oktay S, Alev B, Tunali S, Emekli-Alturfan E, Tunali-Akbay T, Koc-Ozturk L, Yanardag R, Yarat A. Edaravone ameliorates the adverse effects of valproic acid toxicity in small intestine. Human Exp Toxicol. 2015; 34(6): 654-661. [CrossRef]
  • Akinrinade ID, Memudu AE, Ogundele OM. Fluoride and aluminium disturb neuronal morphology, transport functions, cholinesterase, lysosomal and cell cycle activities. Pathophysiology. 2015; 22(2): 105-115. [CrossRef]
  • Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev. 1979; 59(3): 527-605.
  • Martins RN, Harper CG, Stokes GB, Masters CL. Increased cerebral glucose‐6‐phosphate dehydrogenase activity in Alzheimer's disease may reflect oxidative stress. J Neurochem. 1986; 46(4): 1042-1045.
  • Tiwari M. Glucose-6-phsphate dehydrogenase (G6PD) and neurodegenerative disorders: Mapping diagnostic and therapeutic opportunities. Genes Dis. 2018; 4(4): 196-203. [CrossRef]
  • Kalaria RN, Pax AB. Increased collagen content of cerebral microvessels in Alzheimer's disease. Brain Res. 1995; 705(1): 349-352. [CrossRef]
  • Beutler E, Red Cell Metabolism: A Manual of Biochemical Methods, second ed., Grune & Stratton, New York, USA 1975.
  • Ledwożyw A, Michalak J, Stȩpień A, Ka̧dziołka A. The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis. Clin Chim Acta. 1986; 155(3): 275-283.
  • Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 1990; 186: 464-478. [CrossRef]
  • Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, Jungers P, DescampsLatscha B. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int. 1996; 49(5): 1304-1313. [CrossRef]
  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951; 193(1): 265-275.
  • Aebi H, Catalase in vitro. Methods Enzymol. 1984; 105: 121-126. [CrossRef]
  • Mylroie AA, Collins H, Umbles C, Kyle J. Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol. 1986; 82(3): 512-520. [CrossRef]
  • Wendel A. Glutathione peroxidase. Methods Enzymol. 1981; 77: 325-333. [CrossRef]
  • Beutler E, Red Cell Metabolism: A Manual of Biochemical Methods. Grune & Stratton, New York, USA 1971.
  • Wei H, Frenkel K. In vivo formation of oxidized DNA bases in tumor promoter-treated mouse skin. Cancer Res. 1991; 51(16): 4443-4449.
  • Corte ED, Stirpe F. Regulation of xanthine oxidase in rat liver: modifications of the enzyme activity of rat liver supernatant on storage at 20 degrees. Biochem J. 1968; 108(2): 349-351.
  • Furlong CE, Richter R, Seidel S, Motulsky A. Role of genetic polymorphism of human plasma paraoxonase/arylesterase in hydrolysis of the insecticide metabolites chlorpyrifos oxon and paraoxon. Am J Hum Genet. 1988; 43(3): 230-238.
  • Gan KN, Smolen A, Eckerson HW, La Du BN. Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities. Drug Metab Dispos. 1991; 19(1): 100-106.
  • Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961; 7(2): 88-95.
  • Ridderstap A, Bonting S. Na+-K+-activated ATPase and exocrine pancreatic secretion in vitro. Am J Physiol. 1969; 217(6): 1721-1727.
  • Walter K, Schütt C. Alkaline phosphatase in serum (continuous assay). In: Bergmeyer HU. (Ed). Methods in Enzymatic Analysis, Academic Press, New York, USA, 1974; pp.860-864. [CrossRef]
  • Beutler E, Red Cell Metabolism: A Manual of Biochemical Methods, third ed., Grune& Stratton, New York, USA 1984.
  • Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem. 1996; 29(3): 225-229. [CrossRef]
Journal of research in pharmacy (online)-Cover
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  • Yayıncı: Marmara Üniversitesi
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