Effect of prolonged intake of iron enriched diet on testicular functions of experimental rats
Mohamed M. El-Seweidy, Mervat E. Asker, Sousou I. Ali, Hebatallah H. Atteia
DOI: 10.4236/ns.2010.26069   PDF   HTML     5,474 Downloads   11,539 Views   Citations


Iron deficiency anemia represents a common nutritional problem which affects many societies allover the world and iron fortified diet has been suggested as one of possible tools to combat and solve such problem. Present study was designed to illustrate the effect of dietary iron intake on certain biochemical markers dealing with oxidative stress, inflammatory response and cellular alterations of testicular tissues. Adult male rats which were fed on biscuits fortified with iron (0.3% ferrous sulfate) daily for 10 weeks (iron group) showed increased serum iron, ferritin, tumor necrosis factoralpha (TNF-α), nitric oxide (NO) and decreased Testosterone level (p < 0.05). Testicular tissues content of Malondialdehyde (MDA), hydroxyproline (Hyp), iron showed significant increase (p < 0.05) and decreased glutathione (GSH) as compared to control group. Testicular tissues demonstrated massive iron distribution in sertoli interstial tissues and degeneration of germinal epithelial cells. Apparent reduction in number of sperms and spermatogenic cells were also observed. These symptoms may demonstrate that prolonged intake of Biscuit fortified with iron causes certain testicular damage through certain mechanism.

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El-Seweidy, M. , Asker, M. , Ali, S. and Atteia, H. (2010) Effect of prolonged intake of iron enriched diet on testicular functions of experimental rats. Natural Science, 2, 551-556. doi: 10.4236/ns.2010.26069.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Boldt, D.H. (1999) New perspectives on iron: An introduction. American Journal of the Medical Sciences, 318(4), 207-212.
[2] Houglum, K., Filip, M, Witztum, J.L. and Chojkier, M. (1990) Malondialdehyde and 4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload. Journal of Clinical Investigation, 86(6), 1991-1998.
[3] Toyokunis, J. (2002) Iron and carcinogenesis: From fenton reaction to target genes. Redox Report, 7(4), 189-197.
[4] Swanson, C.A. (2003) Iron intake and regulation: Implications for iron deficiency and iron overload. Alcohol, 30(2), 99-102.
[5] Papanikolaou, G. and Pantapoulos, k. (2005) Iron metabolism and toxicity. Toxicology and Applied Pharmacology, 202(2), 199-211.
[6] Richard, A., Johnson, A. C. and Hanson, S. (2005) Parenteral iron compounds sensitize mice to injury-initiated TNF-α mRNA production and TNF-α release. American Journal of Physiology. Renal Physiology, 57(2), F290F297.
[7] Brown, K. E., Meleah, M., Keimberly, A. and weydert, J. (2006) Chronic iron overload stimulates hepatocyte proliferation and cyclin D1 expression in rodent liver. Translational Research, 148(2), 55-62.
[8] Dunger, A., Cunningham, J.M., Delaney, C.A. and Lowe, E. (1990) Tumor necrosis factor-α and Interferone-y inibit insulin secretion and cause DNA damage in unweanled rat islets. Diabetes, 45(2), 183-189.
[9] Alderton, W., Cooper, C. and Knowles, R. (2001) Nitric oxide synthases: Structure, function and inhibition. Biochemical Journal, 357(pt 3), 593-615.
[10] Cornejero, P., Fernandez, V., Vial, M., Videla, L.A. (2007) Hepatoprotective role of NO in an experimental model of chronic iron overload. Nitric Oxide, 16(1), 143-149.
[11] Vogt, H.J., Weidenbach, T., Marqart, K.H. and Vogel, G. (1987) Idiopathic hemochromatosis in a 45 year old infertile man. Androlgia, 19(5), 532-538.
[12] Gupta, R. S., Gupta, E. S., Dhakal, B. K. and Thakur, A. R. (2004) Vitamin C and Vitamin E protect the rat testes from cadmium-induced reactive oxygen species. Mol cells, 17(1), 132-139.
[13] Elmegeed G. A., Ahmed, H. and Hussein, J. S. (2005) Novel synthesized aminsteroidal hetrocycles intervention for inhibiting iron induced oxidative stress Eur. J. Med. Chem. ,40, 1283-1294.
[14] Burits, C. A. and Ashwood, E. R. (1999) Methods for the determination of serum iron, iron binding capacity, and transferrin saturation. In: Tietz Textbook of clinical chemistry, 3rd ed. AACC, 1701-1703.
[15] Moshage, H., Kok, B., Huizenga, J. R., Jansen, P. L. M. (1995) Nitrite and nitrate determination in plasma. A critical evaluation. Clin. Chem. ,41, 892-896.
[16] Chen, W., Jin, W., Cook, M., Weiner, H. L. and Wahl, S. M. (1998) Oral delivery of group a streptococcal cell walls augments circulating TGF. beta and suppresses streptococcal cell wall arthritis. J. Immunol., 161, 6297-6304.
[17] Wheeler, M. J. (1995) The determination of bio-available testosterone.Ann. Clin. Biochem., 32, 345-357.
[18] Lotz, J., Hafner, G. and Prellwitz, W. (1997) Reference study for ferritin assays. Kurzmitteilung Clin. Lab., 43, 993-994.
[19] Buege, J. and Aust, S. (1978) Microsomal lipid peroxidation . Methods Enzymol., 52, 302-306.
[20] Ahmed, A. E., Gamal, I. H., Loh, J. and Abdel-Rahman, S. Z. (1991) Studies on mechanism of haloacetonitrile induced gasyrointestinal toxicity, interaction of dibromoacetonitrile with glutathione as glutath ione-s-transferase in rats. J. Biol. Toxicol., 612, 115-121.
[21] Basset, M. L., Halliday, J. W. and Powell, L. W. (1986) Value of hepatic measurement in early hemochromatosis and determination of the critical iron level associated with fibrosis. Hepatology, 61, 24-29.
[22] Fujita, M., Shannon, J. M., Morikawa, O., Gauldie, J., Hara, N. and Mason, R. J. (2003) Overexpression of tumor necrosis factor-α diminishes pulmonary fibrosis induced by bleomycin or transforming growth Factor-β. Am. J. Respir. Cell Mol. Biol., 29, 669-676.
[23] Zhao, Y., Li, H., Gao, Z. and Xu, H. (2005) Effects of dietary baicalin supplementation on iron overload induced mouse liver oxidative injury. European Journal of Pharmacology, 509, 195-200.
[24] Silvana, M. L., Ribeiro, T., Sliva, M. E., Chianca, D. A., Paula, H. D., Cardoso, L. M., Colombari, E. and Pedrosa, L. (2003) Iron overload in hypercholesterolemic rats affects iron homeostasis and serum lipids but not blood pressure. J. Nutr., 133, 15-20.
[25] Pietrangelo, A., Rocchi, E., Schiaffonati, L., Ventura, E. and Cairo, G. (1990) Liver gene expression during chronic dietary iron overload in rats. Hepatology, 11, 798-804.
[26] Valerio, L. G. Jr. and Petersen, D. R. (2000) Characterization of hepatic iron overload following dietary administration of dicyclopentadienyl iron (ferrocene) to mice: cellular, biochemical, and molecular aspects. Experimental and molecular pathology, 68, 1-12.
[27] Teresa, L., Brissot, P., Ma, W-L. and Weisiger, R. A. (1986) Characterization of non-transferrin-bound iron clearance by rat liver. The Journal of Biological Chemistry, 261, 10909-10914.
[28] Lucesoli, F. and Fraga, C. G. (1999) Oxidative stress in testes of rats subjected to chronic iron intoxication and α-tocopherol supplementation.Toxicology 1999, 132, 179-186.
[29] Galleano, M. and Puntarulo, S. (1997) Dietary α-tocopherol supplementatiom on antioxidant defenses after in vivo iron overload in rats. Toxicology, 124, 73-81
[30] Sylvester, S. R. and Griswold, M. D. (1993) Molecular biology of iron transport in the testis. In: De Krester D. Ed. Molecular Biology of the Male Reproductive System. Academic Press: San Diego, 311-23.
[31] Harandi, A. A., Allameh, A., O´Brien, P. J. (2005) In vivo effects of iron overload on toxicological parameters in isolated hepatocytes obtained from adult rats. FEBS Journal, 272(s1).
[32] Jagetia, G. C., Reddy, T. K., Venkatesha, V. A. and Kedlaya, R. (2004) Influence of naringin on ferric iron induced oxidative damage in vitro. Clin. Chim. Acta, 347, 189-197.
[33] Alidoost, F., Gharagozloo, M., Bagherpour, B., Jafarian, A., Sajjadi, S. E., Hourfar H. and Moayedi, B. (2006) Effects of silymarin on the proliferation and glutathione levels of peripheral blood mononuclear cells from beta-thalassemia major patients. Int. Immunopharmacol. , 6, 1305-1310.
[34] Zhang, Y., Li, H., Zhao, Y. and Gao, Z. (2006) Dietary supplementation of baicalin and quercetin attenuates iron overload induced mouse liver injury. European Journal of Pharmacology, 535, 263-269.
[35] Poli, G. and Parola, M. (1997) Oxidative damage and fibrogenesis. Free Radic. Biol. Med., 22, 287-305.
[36] Lucesoli, F., Caligiuri, M., Roberti, M. F., Perazzo, J. C. and Fraga, C. G. (1999) Dose-dependent increase of oxidative damage in the testes of rats subjected to acute iron overload. Arch. Biochem. Biophys., 372, 37-43.
[37] Tsukamoto, H., Lin, M., Ohata, M., Giulivi, C., French, S.W. and Brittenham G. (1999) Iron primes hepatic macrophages for NF-kB activation in alcoholic liver injury. Am. J. Physiol., 277, G1240-G1250.
[38] Flohe´, L., Brigelius-Flohe, R., Saliou, C., Traber, M. G. and Packer, L. (1997) Redox regulation of NF-kB activation. Free Radic. Biol. Med., 22, 1115-1126.
[39] Li, S., Li, X. and Rozanski, G. J. (2003) Regulation of glutathione in cardiac myocytes. J. Mol. Cell Cardiol., 35, 1145-1152.
[40] Dunger, A., Cunningham, J. M., Delaney, C. A., Lowe, J. E., Green, M.H.L., Bone, A. J. and Green, I. C. (1996) Tumor necrosis factor-α and interferone-γ inhibit insulin secretion and cause DNA damage in unweanted-rat islets. Diabetes , 45, 183-189.
[41] Galleano, M., Simontacchi, M. and Puntarulo, S. (2004) Nitric oxide and iron: Effect of iron overload on nitric oxide production in endotoxemia. Mol. Aspects Med., 25, 141-154.
[42] Kleinert, H., Pautz, A., Linker, K., Schwarz, P. (2004) Regulation of the expression of inducible nitric oxide synthase. Eur. J. Parmacol. , 500, 255-266.
[43] Seracchioli, R., Porcu, F., Colombi, C. (1994) Transfusion-dependent homozygous β-thalassemia major successful twin pregnancy following in-vitro fertilization and tubal embryo transfer. Hum. Reprod. , 9, 1964-1965.
[44] Sparacia, G., Iaia, A., Banco, A., D’Angelo, P. and Lagalla, R. (2000) Transfusional hemochromatosis: quantitative relation of MR imaging pituitary signal intensity reduction to hypogonadotropic Hypogonadism. Radiology, 215, 818-823.
[45] Bergeron, C. and Kovacs, K. (1978) Pituitary siderosis: a histologic, immunocytologic and ultrastructural study. Am. J. Pathol. , 93, 295-310.
[46] Wang, C., Tso, S. and Todd, D. (1989) Hypogonadotropic hypogonadism in severe beta-thalassemia: effect of chelation and pulsatile gonadotropin-releasing hormone therapy. J. Clin. Endocrinol. Metab. , 68, 511-516.
[47] van der Poll, T., Romijn, J. A., Endert, E. and Sauerwein, H. P. (1993) Effects of tumor necrosis factor on the hypothalamic-pituitary-testicular axis in healthy men. Metabolism, 42: 303-307.

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