Volume 11, Issue 6 (9-2013)                   IJRM 2013, 11(6): 487-0 | Back to browse issues page

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Kheradmand F, Nourmohammadi I, Ahmadi-Faghih M A, Firoozrai M, Modarressi M H. Zinc and low-dose of cadmium protect sertoli cells against toxic-dose of cadmium: The role of metallothionein. IJRM 2013; 11 (6) :487-0
URL: http://ijrm.ir/article-1-433-en.html
Zinc and low-dose of cadmium protect sertoli cells against toxic-dose of cadmium: The role of metallothionein
Fatemeh Kheradmand1 , Issa Nourmohammadi2 , Mohamad Amin Ahmadi-Faghih2 , Mohsen Firoozrai2 , Mohammad Hossein Modarressi * 3
1- Department of Biochemistry, Faculty of Medicine and Center for Cellular and Molecular Research, Urmia University of Medical Sciences, Urmia, Iran
2- Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
3- Department of Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran , modaresi@sina.tums.ac.ir
Abstract:   (2468 Views)
Background: The impact of cadmium (Cd) on male infertility may be related to the interaction with metal-binding proteins known as metallothioneins (Mts). Trace elements like zinc (Zn) have protective effects on testicular damage induced by Cd.
Objective: We determined the effect of Zn and low-dose Cd pre-treatment on the expression of Mt1 and Mt2 genes on testicular Sertoli cells.
Materials and Methods: The cultured TM4 mouse sertoli cells were treated with 50 μM ZnSO4 (Zn pre-treated group; ZnPG), 2 μM CdCl2 (Cd pre-treated group; CdPG), or distilled water (DW pre-treated group; DWPG). After 18 hour, all of these groups were exposed to 100 μM CdCl2 for different periods of time (1, 2, 3, and 6 hours). There was also a control group for all three groups, which was treated only with distilled water (without Cd or Zn pre-treatment). Cellular viability, Zn and Cd concentrations and gene expression were assessed by MTT, atomic absorption spectrometry and real time PCR methods, respectively.
Results: The expression of Mt1 and Mt2 genes in ZnPG, CdPG, and DWPG was greater than the control group (p=0.02 and p=0.01, respectively). Cd concentrations in CdPG and DWPG were greater than the control group (p=0.00). Expression of both genes in ZnPG and CdPG increased after 3 hours of treatment and Cd concentration decreased simultaneously, which was more obvious in ZnPG.
Conclusion: Zn and short term low-dose Cd pre-treatment might reduce the adverse effects of Cd by increasing expression of Mts genes in Sertoli cells. The protective effect of Zn was stronger than Cd.
Keywords: Cadmium, Gene expression, Metallothionein, Sertoli cells, Zinc
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Type of Study: Original Article |
References
1. Shimada H, Narumi R, Nagano M, Yasutake A, Waalkes MP, Imamura Y. Strain difference of cadmium-induced testicular toxicity in inbred Wistar-Imamichi and Fischer 344 rats. Arch Toxicol 2009; 83: 647-652. [DOI:10.1007/s00204-009-0442-y]
2. Saygi S, Deniz G, Kutsal O, Vural N. Chronic effects of cadmium on kidney, liver, testis, and fertility of male rats. Biol Trace Elem Res 1991; 31: 209-214. [DOI:10.1007/BF02990191]
3. Kusakabe T, Nakajima K, Suzuki K, Nakazato K, Takada H, Satoh T, et al. The changes of heavy metal and metallothionein distribution in testis induced by cadmium exposure. Biometals 2008; 21: 71-81. [DOI:10.1007/s10534-007-9094-7]
4. Amara S, Abdelmelek H, Garrel C, Guiraud P, Douki T, Ravanat JL, et al. Preventive effect of zinc against cadmium-induced oxidative stress in the rat testis. J Reprod Dev 2008; 54: 129-134. [DOI:10.1262/jrd.18110]
5. Akinloye O, Arowojolu AO, Shittu OB, Anetor JI. Cadmium toxicity: a possible cause of male infertility in Nigeria. Reprod Biol 2006; 6: 17-30.
6. Nava-Hernandez MP, Hauad-Marroquin LA, Bassol-Mayagoitia S, Garcia-Arenas G, Mercado-Hernandez R, Echavarri-Guzman MA, et al. Lead-, cadmium-, and arsenic-induced DNA damage in rat germinal cells. DNA Cell Biol 2009; 28: 241-248. [DOI:10.1089/dna.2009.0860]
7. Waalkes MP. Cadmium carcinogenesis in review. J Inorg Biochem 2000; 79: 241-244. [DOI:10.1016/S0162-0134(00)00009-X]
8. Nzengue Y, Steiman R, Rachidi W, Favier A, Guiraud P. Oxidative stress induced by cadmium in the C6 cell line: role of copper and zinc. Biol Trace Elem Res 2012; 146: 410-419. [DOI:10.1007/s12011-011-9265-9]
9. Siu ER, Mruk DD, Porto CS, Cheng CY. Cadmium-induced testicular injury. Toxicol Appl Pharmacol 2009; 238: 240-249. [DOI:10.1016/j.taap.2009.01.028]
10. Thompson J, Bannigan J. Cadmium: toxic effects on the reproductive system and the embryo. Reprod Toxicol 2008; 25: 304-315. [DOI:10.1016/j.reprotox.2008.02.001]
11. Goyer RA, Liu J, Waalkes MP. Cadmium and cancer of prostate and testis. Biometals 2004; 17: 555-558. [DOI:10.1023/B:BIOM.0000045738.59708.20]
12. Ren XY, Zhou Y, Zhang JP, Feng WH, Jiao BH. Metallothionein gene expression under different time in testicular Sertoli and spermatogenic cells of rats treated with cadmium. Reprod toxicology (Elmsford, NY 2003; 17: 219-227. [DOI:10.1016/S0890-6238(02)00151-X]
13. Xu L, Wang S, Zhao R, Yang X. [Protection of metallothionein on the peroxidative injury in testis induced by cadmium]. Wei Sheng Yan Jiu 2000; 29: 78-79. (In Chinese)
14. Goering PL, Klaassen CD. Altered subcellular distribution of cadmium following cadmium pretreatment: possible mechanism of tolerance to cadmium-induced lethality. Toxicol Appl Pharmacol 1983; 70: 195-203. [DOI:10.1016/0041-008X(83)90095-9]
15. Park JD, Liu Y, Klaassen CD. Protective effect of metallothionein against the toxicity of cadmium and other metals (1). Toxicology 2001; 163: 93-100. [DOI:10.1016/S0300-483X(01)00375-4]
16. Klaassen CD, Liu J, Diwan BA. Metallothionein protection of cadmium toxicity. Toxicol Appl Pharmacol 2009; 238: 215-220. [DOI:10.1016/j.taap.2009.03.026]
17. Jemai H, Lachkar HA, Messaoudi I, Kerkeni A. Effects of zinc pre-treatment on blood glutathione, serum zinc and kidney histological organisation in male rats exposed to cadmium. J Trace Elem Med Biol 2010; 24: 277-282. [DOI:10.1016/j.jtemb.2010.07.001]
18. Benoff S, Hauser R, Marmar JL, Hurley IR, Napolitano B, Centola GM. Cadmium concentrations in blood and seminal plasma: correlations with sperm number and motility in three male populations (infertility patients, artificial insemination donors, and unselected volunteers). Mol Med 2009; 15: 248-262. [DOI:10.2119/molmed.2008.00104]
19. Al-Bader A, Omu AE, Dashti H. Chronic cadmium toxicity to sperm of heavy cigarette smokers: immunomodulation by zinc. Arch Androl 1999; 43: 135-140. [DOI:10.1080/014850199262643]
20. Matsuda Y, Watanabe T. Effects of oyster extract on the reproductive function of zinc-deficient mice: bioavailability of zinc contained in oyster extract. Congenit Anom (Kyoto) 2003; 43: 271-279. [DOI:10.1111/j.1741-4520.2003.tb01013.x]
21. Wei Q, Fan R, Yang X, Chen T. [Effect of zinc on reproductive toxicity in rats]. Wei Sheng Yan Jiu 2003; 32: 618-619. (In Chinese)
22. Li J, Yi J, Wang C, Xu P. [Effect of cadmium on apoptosis of spermatogenic cells of rat testis and the protection effect of zinc against it]. Wei Sheng Yan Jiu 2000; 29: 135-137. (In Chinese)
23. Burukoglu D, Baycu C. Protective effects of zinc on testes of cadmium-treated rats. Bull Environ Contam Toxicol 2008; 81: 521-524. [DOI:10.1007/s00128-007-9211-x]
24. Wahba ZZ, Waalkes MP. Effect of in vivo low-dose cadmium pretreatment on the in vitro interactions of cadmium with isolated interstitial cells of the rat testes. Fundam Appl Toxicol 1990; 15: 641-650. [DOI:10.1016/0272-0590(90)90181-I]
25. Coogan TP. Enhanced metallothionein gene expression is associated with protection from cadmium-induced genotoxicity in cultured rat liver cells. J Toxicol Environ Health 1994; 41 233-245. [DOI:10.1080/15287399409531839]
26. Hu Y, Jin T, Zhou T, Pang B, Wang Y. Effects of zinc on gene expressions induced by cadmium in prostate and testes of rats. Biometals 2004; 17: 571-572. [DOI:10.1023/B:BIOM.0000045835.21954.c7]
27. Messaoudi I, Hammouda F, El Heni J, Baati T, Said K, Kerkeni A. Reversal of cadmium-induced oxidative stress in rat erythrocytes by selenium, zinc or their combination. Exp Toxicol Pathol 2009; 62: 281-288. [DOI:10.1016/j.etp.2009.04.004]
28. Kara H, Karatas F, Canatan H, Servi K. Effects of exogenous metallothionein on acute cadmium toxicity in rats. Biol Trace Elem Res 2005; 104: 223-232. [DOI:10.1385/BTER:104:3:223]
29. Leber AP, Miya TS. A mechanism for cadmium- and zinc-induced tolerance to cadmium toxicity: involvement of metallothionein. Toxicol Appl Pharmacol 1976; 37: 403-414. [DOI:10.1016/0041-008X(76)90202-7]
30. Yang XF, Wang SY, Zhao RC, Ao SQ, Xu LC, Wang XR. Changes in tissue metals after cadmium intoxication and intervention with chlorpromazine in male rats. Biomed Environ Sci 2000; 13:19-25.
31. Dorian C, Klaassen CD. Protection by zinc-metallothionein (ZnMT) against cadmium-metallothionein-induced nephrotoxicity. Fundam Appl Toxicol 1995; 26: 99-106. [DOI:10.1006/faat.1995.1079]
32. Squibb KS, Cousins RJ, Silbon BL, Levin S. Liver and intestinal metallothionein: function in acute cadmium toxicity. Exp Mol Pathol 1976; 25: 163-171. [DOI:10.1016/0014-4800(76)90026-5]
33. Haffor AS, Abou-Tarboush FM. Testicular cellular toxicity of cadmium: transmission electron microscopy examination. J Environ Biol 2004; 25: 251-258.
34. Hosseini-Asl S, Modarressi MH, Atri M, Salhab M, Mokbel K, Mehdipour P. The association between telomerase activity and expression of its RNA component (hTR) in breast cancer patients: the importance of DNase treatment. J Carcinog 2006; 5: 17. [DOI:10.1186/1477-3163-5-17]
35. Espevik T, Lamvik MK, Sunde A, Eik-Nes KB. Effects of cadmium on survival and morphology of cultured rat Sertoli cells. J Reprod Fertil 1982; 65: 489-495. [DOI:10.1530/jrf.0.0650489]
36. Miura N. Individual susceptibility to cadmium toxicity and metallothionein gene polymorphisms: with references to current status of occupational cadmium exposure. Ind Health 2009; 47: 487-494. [DOI:10.2486/indhealth.47.487]
37. Zhang M, He Z, Wen L, Wu J, Yuan L, Lu Y, et al. Cadmium suppresses the proliferation of piglet Sertoli cells and causes their DNA damage, cell apoptosis and aberrant ultrastructure. Reprod Biol Endocrinol 2010; 8: 97. [DOI:10.1186/1477-7827-8-97]
38. Wang SH, Chen JH, Lin LY. Functional integrity of metallothionein genes in testicular cell lines. J Cell Biochem 1994; 55: 486-495. [DOI:10.1002/jcb.240550408]
39. Wahba ZZ, Miller MS, Waalkes MP. Absence of changes in metallothionein RNA in the rat testes made refractory to cadmium toxicity by zinc pretreatment. Hum Exp Toxicol 1994; 13: 65-67. [DOI:10.1177/096032719401300110]
40. Bonda E, Wlostowski T, Krasowska A. Testicular toxicity induced by dietary cadmium is associated with decreased testicular zinc and increased hepatic and renal metallothionein and zinc in the bank vole (Clethrionomys glareolus). Biometals 2004; 17: 615-624. [DOI:10.1007/s10534-004-1226-8]
41. Buhler RH, Kagi JH. Human hepatic metallothioneins. FEBS Lett 1974; 39: 229-234. [DOI:10.1016/0014-5793(74)80057-8]
42. Souza V, Escobar Mdel C, Bucio L, Hernandez E, Gutierrez-Ruiz MC. Zinc pretreatment prevents hepatic stellate cells from cadmium-produced oxidative damage. Cell Biol Toxicol 2004; 20: 241-251. [DOI:10.1023/B:CBTO.0000038462.39859.2f]
43. Mishima A, Yamamoto C, Fujiwara Y, Kaji T. Tolerance to cadmium cytotoxicity is induced by zinc through non-metallothionein mechanisms as well as metallothionein induction in cultured cells. Toxicology 1997; 118: 85-92. [DOI:10.1016/S0300-483X(96)03565-2]
44. Klaassen CD, Liu J, Choudhuri S. Metallothionein: an intracellular protein to protect against cadmium toxicity. Annu Rev Pharmacol Toxicol 1999; 39: 267-294. [DOI:10.1146/annurev.pharmtox.39.1.267]
45. Ren XY, Zhou Y, Zhang JP, Feng WH, Jiao BH. Expression of metallothionein gene at different time in testicular interstitial cells and liver of rats treated with cadmium. World J Gastroenterol 2003; 9: 1554-1558. [DOI:10.3748/wjg.v9.i7.1554]
46. Liu J, Corton C, Dix DJ, Liu Y, Waalkes MP, Klaassen CD. Genetic background but not metallothionein phenotype dictates sensitivity to cadmium-induced testicular injury in mice. Toxicol Appl Pharmacol 2001; 176: 1-9. [DOI:10.1006/taap.2001.9262]
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