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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)

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Abstract

Mechanism of testicular toxicity induced by dietary cadmium (Cd) has been less investigated than that following acute Cd injection. In the present study we characterized testicular injury in a small rodent, the bank vole, exposed subchronically to dietary Cd in a quantity of 0.9 μmol/g, and determined the importance of some factors (Cd accumulation, metallothionein (MT), oxidative stress, and zinc (Zn)) in the injury. Dietary Cd induced moderate histopathological changes (hemorrhage in interstitium, necrosis and apoptosis in seminiferous tubule epithelium) in young (1 month old) bank voles fed, for 6 weeks, Fe-adequate (1.1–1.4 μmol/g) and Fe-enriched (4.5–4.8 μmol/g) diets. In contrast, adult (5 months old) bank voles appeared to be resistant to the toxic effects of dietary Cd, despite the fact that testicular Cd contents were higher and MT levels lower than those in the young animals. The Cd-induced histopathological changes and apoptosis were accompanied by increased testicular lipid peroxidation, decreased testicular Zn concentration and elevated levels of hepatic and renal MT and Zn. Supplemental dietary Zn (1.7–1.8 μmol/g) prevented the Cd-induced testicular Zn depletion and injury. The data indicate that dietary Cd produces testicular lesions indirectly, through decreasing testicular Zn, which seems to be due to the sequestration of this element by the Cd-induced hepatic and renal MT.

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References

  • Beyersmann D, Hechtenberg S. 1997 Cadmium, gene regulation, and cellular signalling in mammalian cells. Toxicol Appl Phar-macol 144, 247–261.

    Google Scholar 

  • Bus JS, Vinegar A, Brooks SM. 1978 Biochemical and physiologic changes in lungs of rats exposed to a cadmium chloride aerosol.Am Rev Resp Dis 118, 573–580.

    Google Scholar 

  • Carey LC, Coyle P, Philcox JC, Rofe AM. 2000 Maternal ethanol exposure is associated with decreased plasma zinc and increased fetal abnormalities in normal but not metallothionein-mull mice.Alkohol Clin Exp Res 24, 213–219.

    Google Scholar 

  • Cassalino E, Calzaretti G, Sblano C, Landriscina C. 2002 Molecu-lar inhibitory mechanism of antioxidant enzymes in rat liver and kidney by cadmium. Toxicology 179, 37–50.

    Google Scholar 

  • Chellman GJ, Shaikh ZA, Baggs RB. 1984 Decreased uptake and altered subcellular disposition of testicular cadmium as possible mechanism of resistance to cadmium-induced testicular necrosis in inbred mice. Toxicology 30, 157–169.

    Google Scholar 

  • Chellman GJ, Shaikh ZA, Bags RB, Diamond GL. 1985 Resistance to cadmium-induced necrosis in testes of inbred mice: Possible role of a metallothionein-like cadmium-binding protein. Toxicol Appl Pharmacol 79, 511–523.

    Google Scholar 

  • Cherian MG, Goyer RA, Delaquerriere-Richardson L. 1976 Cadmium-metallothionein-induced nephrotoxicity. Toxicol Appl Pharmacol 38, 399–408.

    Google Scholar 

  • Coyle P, Philcox JC, Carey LC, Rofe AM. 2002 Metallothionein: The multipurpose protein. Cell Mol Life Sci 59, 627–647.

    Google Scholar 

  • Dalton T, Fu K, Enders GC, Palmiter RD, Andrews GK. 1996 Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium. Environ Health Perspect 104, 68–76.

    Google Scholar 

  • Goering PL, Waalkes MP, Klaassen CD. 1995 Toxicology of cad-mium. In: Goyer RA, Cherian MG, eds. Toxicology of Metals: Biochemical Aspects. New York: Springer; 189–213.

    Google Scholar 

  • Goyer RA, Miller CR, Zhu SY, Victery W. 1989 Non-metallothionein-bound cadmium in the pathogenesis of cadmium nephrotoxicity in the rat. Toxicol Appl Pharmacol 101, 232–244.

    Google Scholar 

  • Groten JP, Sinkeldom EJ, Luten JB, Muys T, van Bladeren PJ. 1991 Interaction of dietary Ca, P, Mg, Cu, Fe, Zn, and Se with the.623 accumulation and oral toxicity of cadmium in rats. Food Chem Toxicol 29, 249–258.

    Google Scholar 

  • Habeebu SS, Liu J, Klaassen CD. 1998 Cadmium-induced apoptosis in mouse liver. Toxicol Appl Pharmacol 149, 203–209.

    Google Scholar 

  • Habeebu SS, Liu J, Liu Y, Klaassen CD. 2000a Metallothionein-null mice are more sensitive than wild-type mice to liver injury induced by repeated exposure to cadmium. Toxicol Sci 55, 223–232.

    Google Scholar 

  • Habeebu SS, Liu J, Liu Y, Klaassen CD. 2000b Metallothionein-null mice are more susceptible than wild-type mice to chronic CdCl 2-induced bone injury. Toxicol Sci 56, 211–219.

    Google Scholar 

  • Kaji T, Mishima A, Yamamoto C, Sakamoto M, Kozuka H. 1993 Zinc protection against cadmium-induced destruction of the monolayer of cultured vascular endothelial cells. Toxicol Lett 66, 247–255.

    Google Scholar 

  • King LM, Bauks WA, George WJ. 1999 Differences in cadmium transport to the testis, epididymis and brain in cadmium-sensitive and-resistant murine strains 129/J and A/J. J Pharmacol Exp Ther 289, 825–830.

    Google Scholar 

  • Klaassen CD, Liu J, Choudhuri S. 1999 Metallothionein: an intra-cellular protein to protect against cadmium toxicity. Annu Rev Pharmacol Toxicol 39, 267–294.

    Google Scholar 

  • Koizumi T, Li ZG. 1992 Role of oxidative stress in single-dose, cadmium-induced testicular cancer. J Toxicol Environ Health A37, 25–36.

    Google Scholar 

  • Kotsonis FN, Klaassen CD. 1978 The relationship of metallo-thionein to the toxicity of cadmium after prolonged oral admin-istration to rats. Toxicol Appl Pharmacol 46, 39–54.

    Google Scholar 

  • Liu J, Corton C, Dix DJ, Liu Y, Waalkes MP, Klaassen CD. 2001 Genetic background but not metallothionein phenotype dictates sensitivity to cadmium-induced testicular injury in mice. Toxicol Appl Pharmacol 176, 1–9.

    Google Scholar 

  • Liu Y, Liu J, Iszard MB, Andrews GK, Palmiter RD, Klaassen CD. 1995 Transgenic mice that overexpress metallothionein-I are pro-tected from cadmium lethality and hepatotoxicity. Toxicol Appl Pharmacol 135, 222–228.

    Google Scholar 

  • Maitani T, Suzuki KT. 1986 Essential metal contents and metallothionein-like protein in testes of mice after cadmium administration. Toxicology 40, 1–12.

    Google Scholar 

  • Mason KE, Burns WA, Smith JC. 1982 Testicular damage associ-ated with zinc deficiency in pre-and post-pubertal rats: response to zinc repletion. J Nut r112, 1019–1028

    Google Scholar 

  • Masters BA, Kelly EJ, Quaite CJ, Brinster RL, Palmiter RD. 1994 Targeted disruption of metallothionein I and II genes increases sensitivity to cadmium. Proc Natl Acad Sci USA 91, 584–588.

    Google Scholar 

  • McKenna IL, Bare RM, Waalkes MP. 1996 Metallothionein gene expression in testicular interstitial cells and liver of rats treated with cadmium. Toxicology 107, 121–130.

    Google Scholar 

  • Nodera M, Yanagisawa H, Wada O. 2001 Increased apoptosis in a variety of tissues of zinc-deficient rats. Life Sci 69, 1639–1649.

    Google Scholar 

  • Nolan CV, Shaikh ZA. 1986 An evaluation of tissue metallothionein and genetic resistance to cadmium toxicity in mice. Toxicol Appl Pharmacol 85, 135–144.

    Google Scholar 

  • Nomiyama K, Nomiyama H. 1998 Cadmium-induced renal dys-function: new mechanism, treatment and prevention. J Trace Elem Exp Med 11, 275–288.

    Google Scholar 

  • Nordberg GF. 1971 Effects of acute and chronic cadmium exposure on the testicle of mice. Environ Physiol 1, 171–187.

    Google Scholar 

  • Nordberg M, Nordberg GF. 2000 Toxicological aspects of metallo-thionein. Cell Mol Biol 46, 451–463.

    Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K. 1979 Assay of lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95, 351–358.

    Google Scholar 

  • Onosaka S, Cherian MG. 1982 Comparison of metallothionein de-termination by polarographic and cadmium saturation methods. Toxicol Appl Pharmacol 63, 270–274.

    Google Scholar 

  • Oteiza PI, Olin KL, Fraga CG, Keen CL. 1995 Zinc deficiency causes oxidative damage to proteins, lipids and DNA in rat testes. J Nut r125, 823–829.

    Google Scholar 

  • Oteiza PI, Adonaylo VN, Keen CL. 1999 Cadmium-induced testes oxidative damage in rats can be influenced by dietary zinc intake. Toxicology 137, 13–22.

    Google Scholar 

  • Parizek J. 1957 The destructive effect of cadmium ion on testicular tissue and its prevention by zinc. J Endocrinol 15, 56–63.

    Google Scholar 

  • Parizek J, Zahor Z. 1956 Effect of cadmium salts on testicular tissue. Nature 177, 1036–1037.

    Google Scholar 

  • Saygi S, Deniz G, Kutsal O, Vural N. 1991 Chronic effects of cad-mium on kidney, liver, testis and fertility of male rats. Biol Trace Elem Res 31, 209–214.

    Google Scholar 

  • Shaikh ZA, Jordan SA, Tewari PC. 1993 Cadmium disposition and metallothionein induction in mice: strain-, sex-, age-, and dose-dependent differences. Toxicology 80, 51–70.

    Google Scholar 

  • Shiraishi N, Uno H, Waalkes MP. 1993 Effect of L-ascorbic acid pretreatment on cadmium toxicity in the male Fisher (F344/NCr) rat. Toxicology 85, 85–100.

    Google Scholar 

  • Suzuki Y, Apostolova MD, Cherian MG. 2000 Astrocyte cultures from transgenic mice to study the role of metallothionein in cytotoxicity of tert-butyl hydroperoxide. Toxicology 145, 51–62

    Google Scholar 

  • Świergosz R, Zakrzewska M, Sawicka-Kapusta K, Bacia K, Janowska I. 1998 Accumulation of cadmium in and its effect on bank vole tissues after chronic exposure. Ecotoxicol Environ Saf 41, 130–136.

    Google Scholar 

  • Waalkes MP, Perantoni A, Bhave MR, Rehm S. 1988 Strain de-pendence in mice of resistance and susceptibility to the testic-ular effects of cadmium: Assessment of the role of testicular cadmium-binding proteins. Toxicol Appl Pharmacol 93, 47–61.

    Google Scholar 

  • Waalkes MP, Anver MR, Diwan BA. 1999 Chronic toxic and car-cinogenic effects of oral cadmium in the Noble (NBL/Cr) rat: induction of neoplastic and proliferative lesions of the adrenal, kidney, prostate, and testes. J Toxicol Environ Health A 58, 199–214.

    Google Scholar 

  • Wahba ZZ, Miller MS, Waalkes MP. 1994 Absence of changes in metallothionein RNA in the rat testes made refractory to cadmium toxicity by zinc pretreatment. Hum Exp Toxicol 13, 65–67.

    Google Scholar 

  • Winge DR, Miklossy KA. 1982 Domain nature of metallothionein. J Biol Che m257, 3471–3476.

    Google Scholar 

  • Włostowski T, Krasowska A. 1999 Subcellular distribution of metallothionein and cadmium in the liver and kidneys of bank voles (Clethrionomys glareolus) exposed to dietary cadmium. BioMetals 12, 173–179.

    Google Scholar 

  • Włostowski T, Krasowska A, Dworakowski W. 1996 Low ambient temperature decreases cadmium accumulation in the liver and kidneys of the bank vole (Clethrionomys glareolus). BioMetals 9, 363–369.

    Google Scholar 

  • Włostowski T, Krasowska A, Bonda E. 2003 An iron-rich diet pro-tects the liver and kidneys against cadmium-induced injury in the bank vole (Clethrionomys glareolus). Ecotoxicol Environ Saf 54, 194–198.

    Google Scholar 

  • Włostowski T, Bonda E, Krasowska A. 2004 Photoperiod affects hepatic and renal cadmium accumulation, metallothionein induc-tion, and cadmium toxicity in the wild bank vole (Clethrionomys glareolus). Ecotoxicol Environ Saf 58, 29–36.

    Google Scholar 

  • Wormser U, Nir I. 1988 Effect of age on cadmium-induced metallo-thionein synthesis in the rat. Arch Toxicol 62, 392–394.

    Google Scholar 

  • Xu C, Johnson JE, Singh PK, Jones MM, Yan H, Carter CE. 1996 In vivo studies of cadmium-induced apoptosis in testicular tissue of.624 the rat and its modulation by a chelating agent. Toxicology 107, 1–8.

    Google Scholar 

  • Xu G, Zhou G, ** T et al. 1999 Apoptosis and p53 gene expression in male reproductive tissues of cadmium exposed rats. BioMetals 12, 131–139.

    Google Scholar 

  • Yiin SJ, Cheru CL, Sheu JY, Lin TH. 1999 Cadmium-induced lipid peroxidation in rat testes and protection by selenium. BioMetals 12, 353–359.

    Google Scholar 

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  1. Institute of Biology, University of Białystok, Świerkowa 20B, 15-950, Białystok, Poland

    Elżbieta Bonda, Tadeusz Włostowski & Alicja Krasowska

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  1. Elżbieta Bonda
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  2. Tadeusz Włostowski
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Bonda, E., Włostowski, 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 17, 615–624 (2004). https://doi.org/10.1007/s10534-004-1226-8

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