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Effects of chronic exposure to cadmium on prostate lipids and morphology

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Abstract

Cadmium is an environmental toxic metal implicated in human prostate carcinogenesis. The mechanism of its toxicity is not fully understood. Previously, we showed that cadmium exposure induces oxidative stress, especially lipid peroxidation. This study evaluates the effect of chronic exposure to 0.886 mM of cadmium (Cd) per liter in the drinking water on prostate lipid content and metabolism in Wistar rats. We determined the lipid profile and measured the expression of lipogenic enzymes: FAS, GPAT, LPL, DGAT-1, DGAT-2, ACO, CPT-1 and CT, and of certain factors involved in lipid regulation and fatty acid transporters: FAT/CD36, E-FABP, SREBP-2, PPAR-γ and PPAR-α by RT-PCR. Ultrastructure was analyzed by electron microscopy and, as prostate is an androgen controlled gland, AR expression was measured by RT-PCR and Western blot. Cd altered the prostatic lipid profile. Triglycerides (TG) and esterified cholesterol (EC) decreased, free cholesterol (FC) and phospholipids (PL) increased and total cholesterol (TC) did not change. FAS, MDH and IDH activities did not vary but G6PDH decreased significantly in Cd group. Regarding TG synthesis, DGAT-1 decreased while GPAT increased and FAS, LPL and DGAT-2 remained unchanged. Regarding beta oxidation, CPT-1 increased while ACO expression decreased in Cd group. In the PL pathway, CT expression was increased. All these results would justify the decrease of TG in Cd group when compared to control. In the cholesterol metabolic pathway, HMGCoAR and SREBP-2 increased. PPAR-α increased but PPAR-γ did not change. Regarding fatty acid transporters, FAT/CD36 decreased, while E-FABP increased. AR mRNA and protein expression decreased. Ultrastructural analysis showed a decrease in lipid droplets and signs of cellular damage in the Cd group.

Cadmium exposure induces important changes in prostatic lipid profile and metabolism, confirmed by the morphology analyses, which also showed signs of cellular damage. These results could be important to further understanding the complex mechanism of cadmium toxicity in prostate and in the development of better treatments for people and animals exposed to the heavy metal.

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Abbreviations

LD50:

medial lethal doses

FAS:

fatty acid synthetase

HMGCoAR:

hydroxymethylglutaryl coenzyme A reductase

GPAT:

glycerol-3-phosphate acyltransferase

DGAT:

diacyl glycerol acyl transferase

LPL:

lipoprotein lipase

FC:

free cholesterol

EC:

esterified cholesterol

TG:

triglycerides

AR:

androgen receptor

CT:

CTP-phosphocholine cytidylyltransferase

DAG:

diacyl glycerol

ACO:

acyl CoA oxidase

CPT-1:

carnitin palmitoil transferase

PC:

phosphatidilcholine

FA:

fatty acids

TBARS:

thiobarbituric acid – reactive susbtances

References

  • Abell LL, Levy BB, Brodie BB, Kendal FE (1952) A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J Biol Chem 195:357–366

    CAS  Google Scholar 

  • Alberts AW, Ferguson K, Hennesy S, Vagelos PR (1974) Regulation of lipid synthesis in cultured animal cells. J Biol Chem 24:5241–5249

    Google Scholar 

  • Alvarez SM, Gomez NN, Scardapane L, Zirulnik F, Martinez D, Gimenez MS (2004) Morphological changes and oxidative stress in rat prostate exposed to a non-carcinogenic dose of cadmium. Toxicol Lett 153:365–376

    Article  PubMed  CAS  Google Scholar 

  • Arienti G, Carlini E, Polci A, Cosmi EV, Palmerini CA (1998) Fatty acid pattern of human prostasome lipid. Arch Biochem Biophys 358:391–395

    Article  PubMed  CAS  Google Scholar 

  • Brown MS, Goldstein JL (1999) A proteolytic pathway that controls the cholesterol content of membranes, cells and blood. Proc Natl Acad Sci USA 96:11041–11048

    Article  PubMed  CAS  Google Scholar 

  • Caisová D, Eybl V (1997) The influence of repeated administration of cadmium and lead on the activity of glutathion peroxidase and lipid peroxidation in mice. Biomarkers Environ 2:57–60

    Article  Google Scholar 

  • Calderoni AM, Oliveros L, Jahn G, Anton R, Luco J, Giménez MS (2005) Alterations in the lipid content of pituitary gland and serum prolactin and growth hormone in cadmium treated rats. BioMetals 18:213–220

    Article  PubMed  CAS  Google Scholar 

  • Carter JM, Waite KA, Campenot RB, Vance JE, Vance DE (2003) Enhanced expression and activation of CTP:phosphocoline cytidylyltransferase β2 during neurite outgrowth. J Biol Chem 278:44988–44994

    Article  PubMed  CAS  Google Scholar 

  • Caviglia JM, Gómez Dumm de INT, Coleman RA, Igal RA (2004) Phosphatidylcholine deficiency upregulates enzymes of triacylglycerol metabolism in CHO cells. J Lipid Res 45:1500–1509

    Article  PubMed  CAS  Google Scholar 

  • Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ (2002) Nuclear receptor and lipid phisiology: opening the X-files. Science 294:1866–1870

    Article  PubMed  CAS  Google Scholar 

  • Clegg MS, Keen CL, Lonnerdal B, Hurley LS (1981) Influence of ashing techniques on the analysis of trace elements in animal tissue. I. Wet-ashing. Biol Trace Elem Res 3:107–115

    Article  CAS  Google Scholar 

  • El-Demerdash FM, Yousef MI, Kedwany FS, Baghdadi HH (2004) Cadmium-induced changes in lipid peroxidation, blood hematology, biochemical parameters and semen quality of male rats: protective role of vitamin E and β-carotene. Food Chem Toxicol 42:1563 – 1571

    Article  PubMed  CAS  Google Scholar 

  • Farrell HM (1980) Purification and properties of NADP-isocitrate dehydrogenase from lactating bovine mammary gland. Archiv Biochem Biophys 204:551–559

    Article  CAS  Google Scholar 

  • Finney RE, Nudelman E, White T, Bursten S, Klein P, Leer LL, Wang N, Waggoner D, Singer JW, Lewis RA. 2000. Pharmacological inhibition of phosphatidylcholine biosynthesis is associated with induction of phosphatidylinositol accumulation and cytolysis of neoplastic cell lines. Cancer Res. 60, 5204–5213

    Google Scholar 

  • Folch J, Less M, Sloane-Stanley GH (1968) A simple method for the isolation and purification of total lipid from animal tissues. J Biol Chem 226:497–509

    Google Scholar 

  • Glock GE, Mc Lean P (1953) Further studies on the properties and assay of glucose-6-phosphate dehydrogenase and 6-phospho-gluconate dehydrogenase of rat liver. Biochem J 55:400–408

    PubMed  CAS  Google Scholar 

  • Guthmann F, Haupt R, Looman C, Spener F, Rustow B (1999) Fatty acid translocase/CD36 mediates the uptake of palmitate by type II pneumocytes. Am J Physiol 277:191–196

    Google Scholar 

  • Guthmann F, Hohoff C, Fechner H et al. (1998) Expression of fatty-acid-binding proteins in cells involved in lung-specific lipid metabolism. Eur J Biochem 253:430–436

    Article  PubMed  CAS  Google Scholar 

  • Hoekstra M, Kruijt JK, Van Eck M, Van Berkel TJ (2003) Specific gene expression of ATP-binding cassette transporters and nuclear hormone receptors in rat liver parenchymal, endothelial, and Kupffer cells. J Biol Chem 278:25448–25453

    Article  PubMed  CAS  Google Scholar 

  • IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans. 1993 Beryllium, cadmium, mercury, and exposures in the glass manufacturing industry. International Agency for Research on Cancer, Lyon, France 58:119–238

    Google Scholar 

  • Igal RA, Caviglia JM, Gomez Dumm IN, Coleman RA (2001) Diacylglicerol generated in CHO cell plasma membrane by phospholipase C is used for tracylglycerol synthesis. J Lipid Res 42:88–95

    PubMed  CAS  Google Scholar 

  • Ihnat M. 1990 Metals and other elements at trace levels in food: arsenic, cadmium, lead, selenium and zinc in food. In: Official Methods of Analysis of AOAC International. Virginia, USA. Chapt. 9

  • Koizumi T, Shirakura H, Kumagai H, Tatsumoto H, Suzuki KT (1996) Mechanism of cadmium-induced cytotoxicity in rat hepatocytes: cadmium-induced active oxygen – related permeability changes of the plasma membrane. Toxicology 114:125–134

    Article  PubMed  CAS  Google Scholar 

  • Koonen DPY, Glatz JFC, Bonen A, Luiken JJFP (2005) Long-chain fatty acid uptake and FAT/CD36 translocation in hert and skeletal muscle. Bioch et Biophys Acta 1736:163–180

    CAS  Google Scholar 

  • Kudo N, Nakagawa Y, Waku K (1990) The effect of cadmium on the composition and metabolism of hepatic fatty acids in zinc-adequate and zinc-deficient rats. Toxicol Lett 50:203–212

    Article  PubMed  CAS  Google Scholar 

  • Kudo N, Nakagawa Y, Waku K (1992) Inhibition of the liberation of arachidonic acid by cadmium ions in rabbit alveolar macrophages. Arch Toxicol 66:131–136

    Article  PubMed  CAS  Google Scholar 

  • Kudo N, Waku K (1996) Cadmium suppresses delta 9 desaturase activity in rat hepatocytes. Toxicology 114:101–111

    Article  PubMed  CAS  Google Scholar 

  • Li M, Kondo T, Zhao QL et al. (2000) Apoptosis induced by cadmium in human lymphoma U937 cells through Ca2+-calpain and caspase-mitochondria-dependent pathways. J Biol Chem 275:39702–39709

    Article  PubMed  CAS  Google Scholar 

  • Martin JJ, Martin R, Codesal J, Fraile B, Paniagua R, Santamaria L (2001) Cadmium chloride – induced dysplastic changes in the ventral rat prostate: an immunohistochemical and quantitative study. Prostate 46:11–20

    Article  PubMed  CAS  Google Scholar 

  • Martin MB, Voeller HJ, Gelmann EP et al. (2002) Role of cadmium in the regulation of AR gene expression and activity. Endocrinology 143:263–275

    Article  PubMed  CAS  Google Scholar 

  • Michaut M, Carrasco M, Gimenez MS (1992) Effects of castration on the incorporation of [3H2O] in lipids of male rat liver. Horm Metab Res 24:593–594

    Article  PubMed  CAS  Google Scholar 

  • Nakamura MT, Cheon Y, Li Y, Nara TY (2004) Mechanisms of regulation of gene expression by fatty acids. Lipids 39:1077–1083

    Article  PubMed  CAS  Google Scholar 

  • Nordberg G (1972) Cadmium metabolism and toxicity. Environ Physiol Biochem 2:7–36

    CAS  Google Scholar 

  • Ochoa S, Mehler AH, Kornberg A (1948) Biosynthesis of dicarboxylic acids by carbon dioxide fixation I. Isolation and properties of an enzyme from pigeon liver catalyzing the reversible oxidation of L-malic acid. J Biol Chem 174:979–1000

    CAS  PubMed  Google Scholar 

  • Ogunlewe JO, Osegbe DN (1989) Zinc and cadmium concentrations in indigenous blacks with normal, hypertrophic, and malignant prostate. Cancer 63:1388 – 1392

    Article  PubMed  CAS  Google Scholar 

  • Ojeda MS, Gomez NN, Gimenez MS (1997) Androgen regulation of lung lipids in the male rat. Lipids 32:57–62

    Article  PubMed  CAS  Google Scholar 

  • Ramírez DC, Gimenez MS (2002) Lipid modification in mouse peritoneal macrophages after chronic cadmium exposure. Toxicology 172:1 – 12

    Article  PubMed  Google Scholar 

  • Rhomberg W, Schmoll HJ, Schneider B (1995) High frequency of metal workers among patients with seminomatous tumors of the testis: a case–control study. Am J Ind Med 28:79 – 87

    Article  PubMed  CAS  Google Scholar 

  • Rong Y, Geng Z, Lau BSH (1996) Ginko biloba attenuates oxidative stress in macrophages and endotelial cells. Free Rad Biol Med 20:121–127

    Article  PubMed  CAS  Google Scholar 

  • Rouser G, Fluster S, Yamamoto A (1970) Two-dimensional thin-layer chromatographic separation of polar lipid and determination of phospholipids analysis of spots. Lipids 5:494–496

    Article  PubMed  CAS  Google Scholar 

  • Sardesai VM, Manning JA (1968) Determination of triglycerides in plasma and tissues. Clin Chem 14:156–161

    CAS  Google Scholar 

  • Shiratori Y, Houweling M, Zha X, Tabas I (1995) Stimulation of CTP:phosphocholine cytidylyltransferase by free cholesterol loading of macrophages involves signaling through protein dephosphorylation. J Biol Chem 270:29894–29903

    Article  PubMed  CAS  Google Scholar 

  • Swinnen JV, Ubrix W, Heyns W, Verhoeven G (1997) Coordinate regulation of gene expression by androgens: evidence for a cascade mechanism involving sterol regulatory element binding proteins. Proc Natl Acad Sci USA 94:12975–12980

    Article  PubMed  CAS  Google Scholar 

  • Swinnen JV, Verhoeven G (1998) Androgens and the control of lipid metabolism in human prostate cancer cells. J Steroid Biochem Molec Biol 65:191–198

    Article  PubMed  CAS  Google Scholar 

  • Terracio L, Nachtigal M (1986) Transformation of prostatic epithelial cells and fibroblasts with cadmium chloride in vitro. Archives of Toxicology 58:141–151

    Article  PubMed  CAS  Google Scholar 

  • US Public Health Service. (1985) Guide to the care and use of laboratory animals. National Institutes of Health, Bethesda MD, 85–23

    Google Scholar 

  • USAF. 1990 Cadmium. In: Installation Restoration Program Toxicology Guide, vol. 5. Harry G, ed. Armstrong Aerospace Medical Research Laboratory, Wright Patterson AFB, OH)

  • Waalkes MP, Rehm S, Riggs CW et al. (1988) Cadmium carcinogenesis in male Wistar [Crl: (WI)BR] rats: dose–response analysis of tumor induction in the prostate and testes and at the injection site. Cancer Res 48:4656–4663

    PubMed  CAS  Google Scholar 

  • Waalkes MP, Rehm S (1994) Cadmium and prostate cancer. J Toxicol Environ Health 43:251–259

    Article  PubMed  CAS  Google Scholar 

  • Wang C, Smith RL (1975) Lowry determination of protein in the presence of Triton X-100. Anal Biochem 63:414–417

    Article  PubMed  CAS  Google Scholar 

  • Waterman IJ, Price NT, Zammit VA (2002) Distinct ontogenic patterns of overt and latent DGAT activities of rat liver microsomes. J Lipid Res 43:1555–1562

    Article  PubMed  CAS  Google Scholar 

  • Zack B, Moss N, Boyle AS, Zlatkis A (1954) Reaction of certain unsaturated steroids with acid iron reagent. Anal Chem 26:776–777

    Article  Google Scholar 

  • Zha S, Ferdinandusse S, Hicks JL et al. (2005) Peroxisomal branched chain fatty acid beta-oxidation pathway is upregulated in prostate cancer. Prostate 63:316–323

    Article  PubMed  CAS  Google Scholar 

  • Zhou YT, Wang ZW, Higa M, Newgard CB, Unger RH (1999) Reversing adipocyte differenciation: implication for treatment of obesity. Proc Natl Acad Sci USA 96:2391–2395

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work has been supported by grant, PIP 4931 from CONICET (National Investigation Council of Science and Technology, Argentina), and Project 8104 from San Luis University, Argentina. MSG, MWF are Career Scientists from CONICET, and SMA has fellowship from CONICET. Authors would like to thank Miss Isabel Sosa, Mr. R. Dominguez for their technical assistance, Dr. Luis D. Martinez for the analysis of cadmium content by ICP-AES in water and prostate samples and Dr. Graciela Jahn and Dr. Silvia Varas for critical reading of the manuscript.

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Authors and Affiliations

  1. Laboratorio de Bioquímica Molecular, Departamento de Bioquímica y Ciencias Biológicas. Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Avenida Ejército de los Andes 950, 5700, San Luis, Argentina

    Silvina Mónica Alvarez, Nidia Noemí Gómez & María Sofía Giménez

  2. Histología y Embriología. Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Avenida Ejército de los Andes 950, 5700, San Luis, Argentina

    Luis Scardapane

  3. IHEM, Universidad Nacional de Cuyo, 5500, Mendoza, Argentina

    Miguel Walter Fornés

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  1. Silvina Mónica Alvarez
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  2. Nidia Noemí Gómez
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  3. Luis Scardapane
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  4. Miguel Walter Fornés
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  5. María Sofía Giménez
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Correspondence to María Sofía Giménez.

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Fellowship from the National Council of Scientific and Technical Investigations (CONICET) – Argentina.

Career Scientific Investigator. National Council of Scientific and Technical Investigations (CONICET) – Argentina.

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Alvarez, S.M., Gómez, N.N., Scardapane, L. et al. Effects of chronic exposure to cadmium on prostate lipids and morphology. Biometals 20, 727–741 (2007). https://doi.org/10.1007/s10534-006-9036-9

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