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Therapeutic Effect of Deferasirox and Glycine on Chronic Cadmium Toxicosis in Rats
Document Type : Original Article
Authors
Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
Abstract
Objective: It has been shown that deferasirox can reduce blood and tissues lead content in animal models. In this study the effect of deferasirox alone or combined with glycine as an antioxidant was evaluated in chronic cadmium toxicosis in rat. Methods: Male wistar albino rats were exposed to 200 ppm cadmium in the drinking water for 3 weeks and treated thereafter with deferasirox (140 mg/kg), glycine (1000 mg/kg) and deferasirox (140 mg/kg) + glycine (1000 mg/kg) by oral gavages, twice daily for 7 days. The effect of these treatments on blood, liver, kidney, bone and testis cadmium values and parameters indicative of oxidative stress (superoxide dismutase, catalase, glutathione peroxidase and total antioxidant capacity in blood) were investigated. Results: Deferasirox was found to be effective in reducing cadmium level in blood, liver and kidney and glycine reduced cadmium levels in bone. Individual administration of deferasirox or glycine mitigated the effects of cadmium on some indicative parameters of oxidative stress in blood. But the best results were obtained following co-administration of both drugs.
Keywords
Subjects
Alcaraz-Contreras, Y., Garza-Oca˜nas, L., Carca˜no-D´ıaz, K., and Ram´ırez-G´omez, X.S. (2011). Effect of Glycine on LeadMobilization, Lead-Induced Oxidative Stress, and Hepatic Toxicity in Rats. Journal of Toxicology,
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doi:10.1155/2011/430539.
Aslani, M., Najarnezhad, V., and Mohri, M. (2009). Individual and Combined Effect of Meso-2, 3- Dimercaptosuccinic Acid and Allicin on Blood and Tissue
Lead Content in Mice. Planta Med, 76:241-244.
Aslani, M.R., Najarnezhad, V., Mohri, M., and Azad, M. (2011). The effect of allicin on blood and tissue lead content in mice. Comp Clin Pathol, 20:121-125.
Balaknina, T., Kosobryukhov, A., Ivanov, A., and Kreslauskii, V. (2005). The effect of cadmium on CO2 exchange, variable fluorescence of chlorophyll and the level of antioxidant enzymes in pea leave. Russian J. Plant Physiol, 52:15-20.
Bray, T.M., and Taylor, C.G. (1993). Tissue glutathione, nutrition and oxidative stress. Can. J. Physiol. Pharmacol, 71:746–775.
Dailiah Roopha, P., Savarimuthu Michael, J., Padmalatha, C., and Ranjit Singh, A.J.A. (2011). Cadmium toxicity exposure – Induced oxidative stress in postnatal development of wistar rats. Journal of Toxicology and Environmental Health Sciences, 3:176-179.
Demirevska, K.K., Simova–Stoilova, L., Stoyamova, Z., and Feller, U. (2006). Cadmium stress in barlely. Growth, leaf pigment and protein composition and detoxification of reactive oxygen species. J. Plant Nutr, 29:451-468.
Gaurav, D., Preet, S., and Dua, K.K. (2010). Chronic cadmium toxicity in rats: treatment with combined administration of vitamins, amino acids, antioxidants and essential Metals. Journal of Food and Drug Analysis, 18:464-470.
Heinz, U., Hegetschweiler, K., Acklin, P., Faller, B., Lattmann, R., and Schnebli, H. (1999). 4-[3, 5-bis (2-hydroxyphenyl)-1, 2, 4-triazol-1-yl]-benzoic acid: a novel fficient and selective iron (III) complexing agent. Angew
Chem Int Ed, 38:2568–2570.
Hendy, G.A.F., Baker, A.J.M., and Evart, C.F. (1992). Cadmium tolerance and toxicity, oxygen radical processes and molecular damage in cadmium tolerant
and cadmium - sensitive clones of Holcuse Ianatees. Acta. Bot. Neerl, 41:271-281.
IARC. (1993). Meeting of the IARC working group on beryllium, cadmium, mercury and exposures in the glass manufacturing industry. Scand. J. Work. Environ. Health, 19:360-363.
Karabulut-Bulan, O., Bolkent, S., Yanardag, R., BilginSokmen, B. (2008). The Role of Vitamin C, Vitamin E, and Selenium on Cadmium-Induced Renal Toxicity of Rats. Drug. Chem. Toxicol, 31:413-426.
Kelley, C., Sargent, D.E., and Uno, J.K. (1999). Cadmium therapeutic agents. Curr. Pharm. Des, 5:229–240.
Kini, R.D., Tripathi, Y., Raghuveer, C., Pai, S.R., Ramaswamy, C., and Kamath. P. (2011). Role of vitamin C as an antioxidant in cadmium chloride testicular damage. International journal of applied biology and pharmaceutical technology, 2:484-488.
Mauriz, J., Matilla, B., Culebras, J., Gonzalez, P., and Gonzalez-Gallego, J. (2001). Dietary glycine inhibits activation of nuclear factor kappa B and prevents liver injury in hemor-rhagic shock in the rat. Free Radical
Biology & Medicine, 31:1236–1244.
Muller, L. (1986). Consequences of cadmium toxicity in rat hepatocytes: mitochondrial dysfunction and lipid peroxidation. Toxicology, 40:285–292.
Najar-Nezhad, V., Aslani, M.R., and Balali-Mood, M. (2008). Evaluation of Allicin for the Treatment of Experimentally Induced Subacute Lead Poisoning in Sheep. Biol. Trace. Elem. Res, 126:141-147.
Najarnezhad, V., Aslani, M., and Balali-Mood, M. (2010). The therapeutic potential of thiamine for treatment of experimentally induced subacute lead poisoning in sheep. Comparative Clinical Pathology, 19:69-73.
Nishida, K., Ohta, Y., and Ishiguro, I. (1997). Glycine facilitates γ-glutamylcysteinylethyl ester-mediated increase in liver glu-tathione level. European Journal of Pharmacology, 333:289–292.
Okoko, T., and Awhin, E.P. (2010). Glycine reduces cadmium-induced alterations in the viability and activation of macrophage U937 cells. Food and Chemical Toxicology, 48:536–538.
Paglia, D.E., and Valentine, W.N. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med, 70:158-169.
Patra, R., Swarup, D., Naresh, R., Kumar, P., Nandi, D., Shekhar, P., Roy, S., and Ali, S. (2007). Tail hair as an indicator of environmental exposure of cows to lead and cadmium in different industrial areas. Ecotoxicology and
Environmental Safety, 66:127-131.
Patra, R.C., Rautray, A.K. and Swarup, D. (2011). Oxidative Stress in Lead and Cadmium Toxicity and Its Amelioration. Veterinary Medicine International, 47-52.
Patra, R.C., Swarup, D., Naresh, R., Kumar, P., Shekhar, P., and Ranjan, R. (2005). Cadmium level in blood and milk from animals reared around different polluting sources in India. Bulletin of Environmental Contamination and
Toxicology, 74:1092-1097.
Patra, R.C., Swarup, D., and Senapat, S.K. (1999). Effects of cadmium on lipid peroxides and superoxide dismutasein hepatic, renal and testicular tissue of rats. Veterinary and Human Toxicology, 41:65-67.
Peters, J.M., Thomas, D., Falk, H., Oberdorster, G., and Smith, T.J. (1986). Contribution of metals to respiratory cancer. Environ Health Perspect, 70:71-83.
SaÃ, ¯d. L., Banni, M., Kerkeni, A., Saïd, K., and Messaoudi, I. (2010). Influence of combined treatment with zinc and selenium on cadmium induced testicular pathophysiology in rat. Food and Chemical Toxicology,48:2759-2765.
Saljooghi, A., and Fatemi, S. (2010). Clinical evaluation of Deferasirox for removal of cadmium ions in rat. Biometals, 23:707-712.
Sarkar, S., Yadav, P., and Bhatnagar, D. (1998). Lipid peroxidative damage on cadmium exposure and alterations in antioxidant system in rat erythrocytes: a
study with relation to time. Bio.Metals, 11:153-157.
Scott, L., and Orvig, C. (2009). Medicinal inorganic chemistry approaches to passivation and removal of aberrant metal ions in disease. Chem. Rev, 109:4885–4910.
Slaughter, M.R., and O’Brien, P.J. (2000). Fully-automated spectrophoto-metric method for measurement of antioxidant activity of catalase. Clin. Biochem, 33:525–534.
Somashekaraiah, B.V., Padmaja, K., and Prasad, A.P.K. (1992). Phytotoxicity of cadmium ion in germinating seedling of mung beam (Phaseoles vulgaris):
Involvement of lipid peroxides in chlorophyll degradation. Phys. Plant, 85:85-89.
Tandon, S.K., and Prasad, S. (2000). Effect of thiamine on the cadmium–chelating capacity of thiol compounds. Hum. Exp. Toxicol, 19:523-528.
Yang, L., Keam, S., and Keating, G. (2007). Deferasirox: a review of its use in the management of transfusional chronic iron overload. Drugs, 67:2211–2230.
Balaknina, T., Kosobryukhov, A., Ivanov, A., and Kreslauskii, V. (2005). The effect of cadmium on CO2 exchange, variable fluorescence of chlorophyll and the level of antioxidant enzymes in pea leave. Russian J. Plant Physiol, 52:15-20.
Bray, T.M., and Taylor, C.G. (1993). Tissue glutathione, nutrition and oxidative stress. Can. J. Physiol. Pharmacol, 71:746–775.
Dailiah Roopha, P., Savarimuthu Michael, J., Padmalatha, C., and Ranjit Singh, A.J.A. (2011). Cadmium toxicity exposure – Induced oxidative stress in postnatal development of wistar rats. Journal of Toxicology and Environmental Health Sciences, 3:176-179.
Demirevska, K.K., Simova–Stoilova, L., Stoyamova, Z., and Feller, U. (2006). Cadmium stress in barlely. Growth, leaf pigment and protein composition and detoxification of reactive oxygen species. J. Plant Nutr, 29:451-468.
Gaurav, D., Preet, S., and Dua, K.K. (2010). Chronic cadmium toxicity in rats: treatment with combined administration of vitamins, amino acids, antioxidants and essential Metals. Journal of Food and Drug Analysis, 18:464-470.
Heinz, U., Hegetschweiler, K., Acklin, P., Faller, B., Lattmann, R., and Schnebli, H. (1999). 4-[3, 5-bis (2-hydroxyphenyl)-1, 2, 4-triazol-1-yl]-benzoic acid: a novel fficient and selective iron (III) complexing agent. Angew
Chem Int Ed, 38:2568–2570.
Hendy, G.A.F., Baker, A.J.M., and Evart, C.F. (1992). Cadmium tolerance and toxicity, oxygen radical processes and molecular damage in cadmium tolerant
and cadmium - sensitive clones of Holcuse Ianatees. Acta. Bot. Neerl, 41:271-281.
IARC. (1993). Meeting of the IARC working group on beryllium, cadmium, mercury and exposures in the glass manufacturing industry. Scand. J. Work. Environ. Health, 19:360-363.
Karabulut-Bulan, O., Bolkent, S., Yanardag, R., BilginSokmen, B. (2008). The Role of Vitamin C, Vitamin E, and Selenium on Cadmium-Induced Renal Toxicity of Rats. Drug. Chem. Toxicol, 31:413-426.
Kelley, C., Sargent, D.E., and Uno, J.K. (1999). Cadmium therapeutic agents. Curr. Pharm. Des, 5:229–240.
Kini, R.D., Tripathi, Y., Raghuveer, C., Pai, S.R., Ramaswamy, C., and Kamath. P. (2011). Role of vitamin C as an antioxidant in cadmium chloride testicular damage. International journal of applied biology and pharmaceutical technology, 2:484-488.
Mauriz, J., Matilla, B., Culebras, J., Gonzalez, P., and Gonzalez-Gallego, J. (2001). Dietary glycine inhibits activation of nuclear factor kappa B and prevents liver injury in hemor-rhagic shock in the rat. Free Radical
Biology & Medicine, 31:1236–1244.
Muller, L. (1986). Consequences of cadmium toxicity in rat hepatocytes: mitochondrial dysfunction and lipid peroxidation. Toxicology, 40:285–292.
Najar-Nezhad, V., Aslani, M.R., and Balali-Mood, M. (2008). Evaluation of Allicin for the Treatment of Experimentally Induced Subacute Lead Poisoning in Sheep. Biol. Trace. Elem. Res, 126:141-147.
Najarnezhad, V., Aslani, M., and Balali-Mood, M. (2010). The therapeutic potential of thiamine for treatment of experimentally induced subacute lead poisoning in sheep. Comparative Clinical Pathology, 19:69-73.
Nishida, K., Ohta, Y., and Ishiguro, I. (1997). Glycine facilitates γ-glutamylcysteinylethyl ester-mediated increase in liver glu-tathione level. European Journal of Pharmacology, 333:289–292.
Okoko, T., and Awhin, E.P. (2010). Glycine reduces cadmium-induced alterations in the viability and activation of macrophage U937 cells. Food and Chemical Toxicology, 48:536–538.
Paglia, D.E., and Valentine, W.N. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med, 70:158-169.
Patra, R., Swarup, D., Naresh, R., Kumar, P., Nandi, D., Shekhar, P., Roy, S., and Ali, S. (2007). Tail hair as an indicator of environmental exposure of cows to lead and cadmium in different industrial areas. Ecotoxicology and
Environmental Safety, 66:127-131.
Patra, R.C., Rautray, A.K. and Swarup, D. (2011). Oxidative Stress in Lead and Cadmium Toxicity and Its Amelioration. Veterinary Medicine International, 47-52.
Patra, R.C., Swarup, D., Naresh, R., Kumar, P., Shekhar, P., and Ranjan, R. (2005). Cadmium level in blood and milk from animals reared around different polluting sources in India. Bulletin of Environmental Contamination and
Toxicology, 74:1092-1097.
Patra, R.C., Swarup, D., and Senapat, S.K. (1999). Effects of cadmium on lipid peroxides and superoxide dismutasein hepatic, renal and testicular tissue of rats. Veterinary and Human Toxicology, 41:65-67.
Peters, J.M., Thomas, D., Falk, H., Oberdorster, G., and Smith, T.J. (1986). Contribution of metals to respiratory cancer. Environ Health Perspect, 70:71-83.
SaÃ, ¯d. L., Banni, M., Kerkeni, A., Saïd, K., and Messaoudi, I. (2010). Influence of combined treatment with zinc and selenium on cadmium induced testicular pathophysiology in rat. Food and Chemical Toxicology,48:2759-2765.
Saljooghi, A., and Fatemi, S. (2010). Clinical evaluation of Deferasirox for removal of cadmium ions in rat. Biometals, 23:707-712.
Sarkar, S., Yadav, P., and Bhatnagar, D. (1998). Lipid peroxidative damage on cadmium exposure and alterations in antioxidant system in rat erythrocytes: a
study with relation to time. Bio.Metals, 11:153-157.
Scott, L., and Orvig, C. (2009). Medicinal inorganic chemistry approaches to passivation and removal of aberrant metal ions in disease. Chem. Rev, 109:4885–4910.
Slaughter, M.R., and O’Brien, P.J. (2000). Fully-automated spectrophoto-metric method for measurement of antioxidant activity of catalase. Clin. Biochem, 33:525–534.
Somashekaraiah, B.V., Padmaja, K., and Prasad, A.P.K. (1992). Phytotoxicity of cadmium ion in germinating seedling of mung beam (Phaseoles vulgaris):
Involvement of lipid peroxides in chlorophyll degradation. Phys. Plant, 85:85-89.
Tandon, S.K., and Prasad, S. (2000). Effect of thiamine on the cadmium–chelating capacity of thiol compounds. Hum. Exp. Toxicol, 19:523-528.
Yang, L., Keam, S., and Keating, G. (2007). Deferasirox: a review of its use in the management of transfusional chronic iron overload. Drugs, 67:2211–2230.
Volume 3, Issue 3 - Serial Number 3
September and October 2015Pages 231-236
- Receive Date 05 September 2015
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