Hepatoprotective effect of Zinc and Magnesium against subchronic Cadmium toxicity on biochemical, histopathological and neurobehavioral parameters in Wistar rats
Mohamed Kouadria, Samir Djemli, Abdelkrim Tahraoui
Abstract
The aim of this study was carried out to investigate the possible hepato protective effect of Zinc and Magnesium against subchronic cadmium toxicity on biochemical, histopathological and neurobehavioral parameters in Wistar rats during 90 days. Fourty Wistar rats, were randomly divided in four experimental group: 1, control only water; 2, water and oral administration (Cd); 3, (Cd+Mg) in water oral administration; 4, (Cd+Zn) in water oral administration. Zinc and Magnesium was used to reduce hepatoxicity and neurobehavioral disorders induced by Cadmium in Wistar rats. The Cd-Zn and Cd-Mg groups received 10 mg/kg of ZnCl2, 10 mg/kg of MgCl2 added to drinking water. The Cd group received 15mg / kg of CdCl2. Blood glucose level and body weight were measured every day. According to the results, which have been obtained. There was a reduction in body weight gain due to Cd group and an increase liver weight. The results indicated also changes in biochemical parameters, which are characterized by an increase in serum glucose, serum urea, serum creatinine, of animals contaminated with cadmium compared to the control animals. However, the supplementation of (Zn) and Mg combination improved some but not all the previous parameters. Moreover, the findings showed variation in hematological parameters of Cd treated animals. In other word, there was a rise in number of white cells, and reduction of red cells counts, hemoglobin concentration and hematocrit percentage, but all these parameters returned approximately to their normal values after combined Zn and Mg addition. The neurobehavioral test shows an increase in the number of cells crossed, the number of straightening in the test. Open field in the group exposed to Cd resulting in locomotors hyperactivity compared to the control and it is minimal in other groups treated with Zn and Mg. On the other hand, the elevated plus maze (EPM) revealed an increase of the time spent in the closed arms of the cadmium group compared to the control. The results clearly showed also deteriorations of liver structure tissue in comparison with the controls, including extensive degeneration of hepatocytes with necrosis, inflammation, the presence of cellular debris within a central vein and cytological vacuolization. The present investigation indicated that Cd had toxicity effects on the previous mentioned parameters. However, the supplementation of combined Zn and Mg was ameliorated some of these parameters and reduced liver histological alterations caused by Cd toxicity.
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References
Ambali SF, Shuaib K, Edeh R, Orieji BC, Shittu M, Akande M (2011) Hyperglycemia induced by subchronic co-administration of chlorpyrifos and lead in Wistar rats: Role of pancreatic lipoperoxidation and alleviating effect of vitamin C. Biology and Medicine 3:6-14.
Andersen O, Nielsen JB, Nordberg GF (2004) Nutritional interactions in intestinal cadmium uptake-possibilities for risk reduction. Biometals 17:543-7.
Bernard A, Roels H, Buchet JP, Cardenas A, Lauwerys R (1992) Cadmium and health: the Belgian experience. IARC Scientific Publications 118:15-33
Bettger JW and Dell BL (1981) Critical physiological role of zinc in the structure and function of biomembranes. Life Sci 28:1425–1438.
Brzoska M, Moniuszko-Jakoniuk J (2000) Interactions between cadmium and zinc in the organism. Food Chem Toxicol 39:967–80.
Brzóska MM, Moniuszko-Jakoniuk J, Piłat-Marcinkiewicz B, Sawicki B (2002)Liver and kidney function and histology in rats exposed to cadmium and ethanol. Alcohol Alcohol 38:2-10.
Bulat ZP, Djukić-Cosić D, Malicević Z, Bulat P, Matović V (2008) Zinc or magnesium supplementation modulates cd intoxication in blood, kidney, spleen, and bone of rabbits. Biol Trace Elem Res 124:110-114
Cempel M and Janicka K (2002) Distribution of nickel, zinc, and copper in rat organs after oral administration of nickel (II) chloride. Biol Trace Elem Res 90:215–226.
Cernaki Savic V, Kotur J, Prokic CV, Kuljic BD, Grbovic Veljovic M (2000) Alterations in magnesium and oxidative status during chronic emotional stress. Magnesium Research 13:29-36.
Comhair SA and Erzurum SC (2002) Antioxidant responses to oxidant-mediated lung diseases. Am Physiol Lung Cell Mol Physiol. 283:246-255.
Contribution à l’étude de conduites émotionnelles chez le rat: Utilisation du handling postnatal et de l’approche éthoexpérimental du comportement (2002) Thèse de doctorat, Université de Rouen, France.
Dawson GR, Crawford SP, Collinson N, Iverson SD and Tricklebank MD (1995) Evidence that the anxiolytic-like effects of chlordiazepoxide on the elevated plus maze are confounded by increases in locomotor activity. Psychopharmacology 118:316-323.
Dhawan D and Goel A (1996) Further evidence for zinc as a hepatoprotective agent in rat liver toxicity. Exp Mol Pathol 63110-117.
Dhawan D, Goel A, Gautam CS (1992) Effects of zinc intake on liver enzymes in carbontetrachloride induced liver injury. Med Sci Res 20:55-56.
Djemli S, Fraia A, Frih H, Bachir A, Zaafour M and Djenidi R (2015) Neurobehavioral Effects of Dexamethasone (Inhibition of Adrenal Axis) in Male Mice Mus musculus. Global Veterinaria 15:545-553.
Djemli S, Zine Kechrid Z, Djabar MR (2010) Combined protective effect of zinc and vitamin C on nickel-induced oxidative liver injury in rats. Scholar Research Library: Annals of Biological Research 3:3278-3286.
Djukić-Cosić D, Ninković M, Malicević Z, Matović V, Soldatović D (2007) Effect of magnesium pretreatment on reduced glutathione levels in tissues of mice exposed to acute and subacute cadmium intoxication: a time course study. Magnes Res 20:177-186.
Dormer RL, Kerbey AL, McPherson M, Manley S, Ashcroft JH, Schofield JG, Randle PJ (1976) The effect of nickel on secretory systems: Studies on the release of amylase, insulin and growth hormone. Biochemistry 140:135-140.
Drury RA, Wallington EA (1980) Carletons histological techniques. Oxford University Press, London, New York Toronto.
El-Refaiy AI, Eissa FI (2012) Protective effects of ascorbic acid and zinc against cadmium-induced histopathological, histochemical, and cytogenetic changes in rats. Comunicata Scientiae 3:162-180.
Erdogan Z, Erdogan S, Celik S, Unlu V (2005) Effects of ascorbic acid on cadmium-induced oxidative stress and performance of broilers. Biol Trace Elem Res 104:19-31.
Finco DR, Kamekeo JJ, Harvey JW, Bruce ML (1997) Kideny fuctions in Clinical Biochemestiry of Domestic Animals. Academic press, San Diego, California. pp. 462-478.
Fraia A, B Ali Rachedi, S Zouiche, S. Djemli and H. Frih (2015) Polyphenon E Could Improve Negative Disorders Changes Caused by Chronic Mild Stress in Male, Wistar Rats. Global Veterinaria 4:478-489.
Golf SW, Bender S, Gruttner J (1998) The significance of magnesium in extreme physical stress. Cardiovascular Drugs and Therapy 12:197-202.
Gurer H, Ozunes H, Neal R, Spitz DR, Ercal N (1998) Antioxidants effects of N-acetylcysteine and succimer in red blood cells from lead exposed rats. Toxicology 120:181-189.
Hossam El Din Omar, Ahmed Ibrahim, Marwa Magdy, Emad Ahmed (2016) The protective effects of zinc and vitamin E supplementation against kidney toxicity by lithium in rats.European Journal of Biological Research 6:21-27.
Kaplan A (1984) Glucose.Clin.Chem.Toronto. Princeton. pp 1032-1036.
Kaplan A (1984) Urea.Clin.Chem. Toronto. Princeton. pp 1257-1260.
Kostic MM, Ognjanovic B, Dimitrijevic S, Zikic RV, Stajnrosic GL,Zivkovic, RV (1993) Cadmium-induced changes of antioxidant and metabolic status in red blood cells of rats: in vivo effects. Eur. J. Haematol 51:86-92.
Kusal KD, Swastika ND, Shakuptala D (2001) The influence of ascorbic acid on nickel induced hepatic lipid peroxidation in rats. Basic Clin Physiol Pharmac 12:187-195.
M Kouadria, S Djemli, A Tahraoui (2019) The protective effect of Zinc and Magnesium against subchronic Cadmium toxicity in Wistar rats (Biochemical and neurobehavioral effects). Asian Journal of Pharmaceutical and Clinical Research 12:217-225.
Mahran AA, Osman HEH, El-Mawla AMAA, Attia AM (2011) Protective effect of zinc (Zn) on the histology and histochemistry of liver and kidney of albino rat treated with cadmium. J Cytol Histol 2:2-9.
Massanyi P, Toman R, Valent M, Cupka P (1995) Evaluation of selected parameters of a metabolic profile and levels of cadmium in reproductive organs of rabbits after an experimental administration. Acta Physiologica andt Hung 83:267–273.
Matović V, Buha A, Bulat Z, Đukić-Ćosić D (2011) Cadmium toxicity revisited: focus on oxidative stress induction and interactions with zinc and magnesium. Arhiv za higijenu rada toksikologiju. 1:65-75.
Matović V, Buha A, Bulat Z, Đukić-Ćosić D (2011) Cadmium toxicity revisited: focus on oxidative stress induction and interactions with zinc and magnesium. Arhiv za higijenu rada toksikologiju. 1:65-75.
Matovic V, Bulat ZP, Dukic-cosic D, Soldatovic D (2004) Zinc, copper, or magnesium supplementation against cadmium toxicity. New York: Nova Science Pub Inc.
Merali Z, Singhal R (1976) Prevention by zinc of cadmiuminduced alterations in pancreatic and hepatic functions. British Journal of pharmacology 57:573-579.
Montgomery K C (1955) The relationship between fear induced by novel stimulation and exploratory behaviour. J. Comp Physio Psychol 48:254-260.
Murry R (1984) Alanine aminotransferase. Clin. Chem. Toronto. Princeton. pp. 1117-1121.
Murry R (1984) Aspartate aminotransferase. Clin. Chem. Toronto. Princeton. pp. 1112-1116.
Murry RL (1984) Creatinine. Clin. Chem. Toronto Princeton. pp 1261-1266.
Nemmiche, D, Chabane, S, Guiraud, P (2007) Role of alpha-tocopherol in cadmium induced oxidative stress in Wistar rat's blood, liver and brain. Chem. Biol. Interact. 170:221-30.
Nepton Soltani, Mansoor Keshavarz, Hamid Sohanaki, Ahmed Reza Dehpour,Saleh Zahedi Asl (2005) Oral magnesium administration prevents vascular complications in STZ –diabetics rats. Life Sciences 76:1455-1464.
Nic Dhonnchadha BA, Bourin M and Hascoët M (2003) Anxiolytic-like effects of 5-HT2 ligands on three mouse models of anxiety. Behav Brain Res 140:203-214.
Noël L, Huynh-Delerme C, Guérin T, Huet H, Frémy J-M, Kolf-Clauw M (2006) Cadmium accumulation and interactions with zinc, copper, and manganese, analysed by ICP-MS in a longterm Caco-2 TC7 cell model. Biometals. 19:473-81.
Obaiah Jamakala A, Usha Rani (2014) Mitigating role of Zinc and Iron against Cadmium induced toxicity liver and kidney of male albino Wistar: a study with reference to Metallothioneine quantification. Int J Pharm Pharm Sci 6:411-417.
Pari L, Murugavel P (2005) Role of diallyl tetrasulfide in ameliorating the cadmium induced biochemical changes in rats. Environ. Toxicol. Pharmacol 20:493-500.
Rana SV, Rekha S, Seema V (1996) Protective effects of few antioxidants on liver function in rats treated with cadmium and mercury. Indian Journal of Experimental Biology 34:177–179.
Rogalska J, Brzóska MM, Roszczenko A, Moniuszko-Jakoniuk J (2009) Enhanced zinc consumption prevents cadmium-induced alterations in lipid metabolism in male rats. Chemico-biological interactions 177:142-52.
Sameeh A, Mansour Abdel-Tawab, Mossa H (2009) Lipid peroxidation and oxidative stress in rat erythrocytes induced by chloropyrifos and the protective effect of zinc. Pesticide Biochemistry and Physiology 93:34-39.
Santon A, Irato P, Medici V, D’Inca R, Albergoni LV, Sturniolo GC (2003) Effect and possible role of Zn treatment in LEC rats, an animal model of Wilson’s disease. Biochim Biophys Acta 1637:91-97.
Sidhu P, Singh N, Shahi JS, Garg ML, Dhawan DK (2003) Hepatotoxic effects of differential doses of nickel—a biochemical and elemental profile study. Vinbull 8:589-593.
Sidhu P, Singh N, Shahi J S, Garg ML, Dhawan DK (2006) Zinc protects rat liver histo-architecture from determined effects of nickel. Bio.Metals 19:301-313.
Silvina Alvarez, Nidia Gomez, Luis Scardapane, Fanny Zirulnik, Dante Martinez, Maria Sofia Gménez (2004) Morphological changes and oxidative stress in rat prostate exposed to a non carcinogenic dose of cadmium.Toxicology letters. 153:365-376.
Simons JE, Yang RSH, Berman E (1995) Evaluation of the mixtures containing organic metals advantages and deasvantages of the use of red world complex mixtures. Environ Health Perspect 103:67-71.
Slotkin TA, Mac Killop EA , Ryde IT,Tate CA, Seidler FJ (2007) Screening for developmental neurotoxicity using PC12 cells: comparisons of organophosphates with a carbamate, anorganochlorine, and divalent nickel. Environ Health Perspect 115:93-101.
Smialowicz RJ, Rogers RR, Riddle MM, Leubke Fogelson LD, Rowe DG (1987) Effects of manganese, calcium, magnesium, and zinc on nickel induced suppression of murine natural killer cell activity. Toxicol Environ Health 20:67-80.
Soldatovic D, Vujanovic D, Matovic V,Plamenac Z (1997) Compared effects of high oral Mg supplements and of EDTA chelating agent on chronic lead intoxication in rabbits. Magnesium research: official organ of the International Society for the Development of Research on Magnesium 10:127-33.
Solomons NW, Viteri F, Shuler TR, Nielsen FH (1982) Bioavailability of nickel in man effects of foods and chemically defined dietary constituents on the absorption of inorganic nikel. Nutr 112:39-50.
Soubrié D (1971) Open-Field chez le rat: inter-relations entre locomotion exploration et emotivité. Journal of Pharmacology 2:457-472.
Sugiwara N (1977) Inhibitory effect of cadmium on calcium absorption from the rat duodenum. Arch. Environ. Contam Toxicol 5:167-175.
Sunderman Jr, Kasprzak KS, Horak E, Gitltz P, Onkelinx C (1976) Effect of triethylenetetramine upon the metabolism and toxicity of 63NiCl2 in rats. Toxicology Applied Pharmacology 38:177-188.
Tandon A, Nagpaul JP, Bandhu H, Singh N, Dhawan D (1999) Effect of lithium on hepatic and serum elemental status under different dietary protein regimens. Biol Trace Elem Res 68:51-62.
Tandon SK, Singh S, Prasad S, Mathur N (2001) Hepatic and renal metallothionein induction by an oral equimolar dose of zinc, cadmium or mercury in mice. Food Chem Toxicol 39:571–577.
Treit D M, Menard J, Royan C (1993) Anxiogenic stimuli in the elevated plus-maze. Pharmacol Biochem Béhaï 44:463-469.
Uyanik F, Eren M, Atasever A, Tuncoku G, Kolsuz AH (2001) Changes in some biochemical parameters and organs of broilers exposed to cadmium and effect of Zinc on cadmium induced alteration. Israel Veterinary Medicine 56:128-134.
Waalkes MP, Kasprzak KS, Oshima M, Poirier LA (1985) Protective effects of zinc acetate towards the toxicity of nickelous acetate in rats. Toxicology 39:29-41.
Washko PW, Cousins RJ (1977) Metabolism of Cd109 in rats fed normal and low-calcium diets. Toxicol Environ Health 1056-1066.
WHO (World Health Organisation) (1992) Environmental Health Criteria, 134Cadmium. IPCS: Geneva.
Submitted date:
10/10/2019
Accepted date:
11/03/2019