Abstract
The effects of latent iron deficiency combined with parenteral subchronic or acute cadmium exposure during pregnancy on maternal and fetal tissue distribution of cadmium, iron and zinc, and on fetal viability were evaluated. Timed-pregnant Sprague-Dawley rats were fed on semisynthetic test diets with either high iron (240 mg kg) or low iron (10 mg kg), and concomitantly exposed to 0, 3 or 5 mg cadmium (as anhydrous CdCl2) per kilogram body weight. Animals were exposed to cadmium from gestation day 1 through 19 by subcutaneously implanted mini pumps (Subchronic exposure) or on gestation day 15 by a single subcutaneous injection (Acute exposure). All rats were killed on gestation day 19. Blood samples, selected organs and fetuses were removed and prepared for element analyses by atomic absorption spectrometry. Low iron diet caused decreases in maternal body weight, maternal and fetal liver weights, placental weights and tissue iron concentrations. By cadmium exposure, both subchronic and acute, tissue cadmium concentrations were increased and the increase was dose-related, maternal liver and kidney zinc concentrations were increased, and fetal zinc concentration was decreased. Cadmium concentration in maternal liver was additionally increased by low iron diet. Acute cadmium exposure caused lower maternal body and organ weights, high fetal mortality, and decreased fetal weights of survivors. In conclusion, parenteral cadmium exposure during pregnancy causes perturbations in essential elements in maternal and fetal compartments. Acute cadmium exposure in the last trimester of gestation poses a risk for fetal viability especially when combined with low iron in maternal diet.
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References
Ahokas RA, Dilts PV. 1979 Cadmium uptake by the rat embryo as a function of gestational age. Am J Obstet Gynecol 135, 219–222.
Akesson A, Berglund M, Schutz A, Bjellerup P, Bremme K, Vahter M. 2002 Cadmium exposure in pregnancy and lactation in relation to iron status. Am J Publ Health 92, 284–287.
Andrews NC, Fleming MD, Gunshin H. 1999 Iron transport across biologic membranes. Nutr Rev 57, 114–123.
Ashby SL, King LJ, Parke VW. 1980 Effect of acute administration of cadmium on the disposition of copper, zinc, and iron in the rat. Environ Res 21, 177–185.
Beard JL. 2000 Iron requirements in adolescent females. J Nutr 130, 440S–442S.
Beard JL. 2001 Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr 131, 568S–580S.
Berglund M, Akesson A, Nermell B, Vahter M. 1994 Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake. Environ Health Perspect 102, 1058–1066.
Bhattacharyya MH, Wilson AK, Rajan SS, Jonah M. 2000 Biochemical pathways in cadmium toxicity. In: Zalups RK, Koropatnick J, eds. Molecular Biology and Toxicology of Metals. London/New York: Taylor & Francis; 34–74.
Bin QH, Garfinkel D. 1994 The cadmium toxicity hypothesis of aging: A possible explanation for the zinc deficiency hypothesis of aging. Med Hypotheses, 42, 380–384.
Blanuša M, Breški Ð. 1981 Comparison of dry and wet ashing procedures for cadmium and iron determination in biological material by atomic-absorption spectrophotometry. Talanta 28, 681–684.
Blanuša M, Kralj Z, Bunarević A. 1985 Interaction of cadmium, zinc and copper in relation to smoking habit, age and histopathological findings in human kidney cortex. Arch Toxicol 58, 115–117.
Blanuša M, Telišman S, Hršak J, Fugaš M, Prpić-Majić D, Šarić M. 1991 Assessment of exposure to lead and cadmium through air and food in inhabitants of Zagreb. Arh Hig Rada Toksikol 42, 257–266.
Blanuša M, Bremner I, SchÖnwald N, Piasek M, Košićek M. Kostial K. 1993 Influence of maternal iron deficiency and cadmium exposure on trace element status of suckling rats. In: Anke M, Meissner D, Mills CF, eds. Trace Elements in Man and Animals-TEMA 8. Gersdorf, Germany: Verlag Media Touristik; 955–958.
Bremner I. 1987 Nutritional and physiological significance of metallothionein. Experientia Suppl 52, 81–107.
BrzÓska MM, Moniuszko-Jakoniuk J. 2001 Interaction between cadmium and zinc in the organism. Food Chem Toxicol 39, 967–980.
Carmichael NG, Backhouse BL, Winder C, Lewis P. 1982 Teratogenicity, toxicity and perinatal effects of cadmium. Human Toxicol 1, 159–186.
Chan HM, Cherian MG. 1993 Mobilization of hepatic cadmium in pregnant rats. Toxicol Appl Pharmacol 120, 308–314.
Crowe A, Morgan EH. 1997 Effect of dietary cadmium on iron metabolism in growing rats. Toxicol Appl Pharmacol 145, 136–146.
Cukerski MA, Sina JL, Prahalada S. Robertson RT. 1991 Effects of seminal vesicle and coagulating gland ablation on fertility in rats. Reprod Toxicol 5, 347–352.
Cook JD. 1999 Defining optimal body iron. Proc Nutr Soc 58, 489–495.
DiDonato M, Sarker B. 2000 Metal transport and metabolism, In: Zalups RK, Koropatnick J, eds. Molecular Biology and Toxicology of Metals. London/New York: Taylor & Francis: 150–178.
Donangelo CM, Woodhouse LR, King SM, Viteri FE, King JC. 2002 Supplemental zinc lowers measures of iron status in young women with low iron reserves. J Nutr 132, 1860–1864.
Dorian C, Gattone VH II, Klaasen CD. 1995 Discrepancy between the nephrotoxic potencies of cadmium-metallothionein and cadmium chloride and the renal concentration of cadmium in the proximal convoluted tubules. Toxicol Appl Pharmacol 130, 161–168.
Elsenhans B, Kolb K, SchÜmann K. Forth W 1994. The longitudinal distribution of cadmium, zinc, copper, iron, and metallothionein in the small-intestinal mucosa of rats after administration of cadmium chloride. Biol Trace Elem Res 41, 31–46.
Flanagan PR, McLellan JS, Haist J, Cherian MG, Chamberalin MJ, Valberg LS. 1978 Increased dieatry cadmium absorption in mice and human subjects with iron deficiency. Gastroneterology 74: 841–846.
Goyer RA. 1995 Transplacental transfer of lead and cadmium. In: Goyer RA, Cherian MG, eds. Toxicology of Metals. Biochemical Aspects. Berlin-Heidelberg, Germany: Springer-Verlag; 1–17.
Groten JP, Sinkeldam EJ, Muys T, Luten JB, van Bladeren PJ. 1991. Interaction of dietary Ca, P, Mg, Mn, Cu, Fe, Zn and Se with the accumulation and oral toxicity of cadmium in rats. Food Chem Toxicol 29, 249–258.
Groten JP, Luten JB, van Bladern PJ. 1992. Dieatry iron lowers the intestinal uptake of cadmium-metallothionein in rats. Eur J Pharmacol-Environ Toxicol Pharmacol Section 228, 23–28.
Hamilton DL, Valberg LS. 1974 Relationship between cadmium and iron absorption. Am J Physiol 227, 1033–1037.
JÄrup L, Berglund M, Elinder CG, Nordberg G, Vahter M. 1998 Health effects of cadmium exposure-a review of the literature and risk estimate. Scand J Work Environ Health 24 (Suppl 1), 1–52.
Jin T, Lu J, Nordberg M. 1998 Toxicokinetics and biochemistry of cadmium with special emphasis on the role of metallothionein. NeuroToxicol 19, 529–536.
Kollmer WE, Berg D. 1989 The influence of a zinc-calcium-or iron-deficient diet on the resorption and kinetics of cadmium in the rat. In: Southgate DAT, Johnson IT, Fenwick GR, eds. Boiavailability 88-Nutrient Availability: Chemical and Biological Aspects. Special Publ No. 72. Cambridge, UK: The Royal Society of Chemistry; 287–289.
LÖnnerdall B. 2000 Dietary factors influencing zinc absorption. J Nutr 130, 1378S–1383S.
Matek Sarić M, Blanuša M, Piasek M, Varnai VM, Jureša D, Kostial K. 2002 Effect of dietary calcium on cadmium absorption and retention in suckling rats. Bio Metals 15, 175–182.
Monsen ER. 1999 The ironies of iron. Am J Clin Nutr 69, 831–832.
Naismith DJ, Binns NM. 1978 Foetal accumulation of iron and copper in maternal protein deprivation. Proc Nutr Soc 37, 54A.
Nordberg M. Winblad B. Basun H. 2000 Cadmium concentration in blood in an elderly urban population. BioMetals 13, 311–317.
Oishi S. Nakagawa J. Ando M. 2000 Effects of cadmium administration on the endogenous metal balance in rats. Biol Trace Elem Res 76, 257–278.
Park JD, Cherrington NJ, Klaassen CD. 2002 Intestinal absorption of cadmium is associated with divalent metal transporter 1 in rats. Toxicol Sci 68, 288–294.
Petering HG, Choudhury H, Stemmer KL. 1979 Some observations of oral ingestion of cadmium on zinc, copper, and iron metabolism. Environ Health Perspect 28, 97–106.
Piasek M, Laskey JW. 1994 Acute cadmium exposure and ovarian steroidogenesis in cycling and pregnant rats. Reprod Toxicol 8, 495–507.
Piasek M, SchÖnwald N, Blanuša M, Kostial K, Laskey JW. 1996 Biomarkers of heavy metal reproductive effects and interaction with essential elements in experimental studies on female rats. Arh Hig Rada Toksikol 47, 245–259.
Piasek M, Blanuša M, Kostial K, Laskey JW. 2001 Placental cadmium and progesterone concentrations in cigarette smokers. Reprod Toxicol 15, 673–681.
Radi SA, Pond WG. 1979 Effects of dietary cadmium on fate of parenterally administered 59Fe in the weanling pig. Nutr Rep Int 19, 695–699.
Ragan HA. 1977 Effects of iron deficiency on the absorption and distribution of lead and cadmium in rats. J Lab Clin Med 90, 700–796.
Reeves PG, Chaney RL. 2001 Mineral status of female rats affects the absorption and organ distribution of dietary cadmium derived from edible sunflower kernels (Helianthus annus L.). Environ Res A 85, 215–225.
Sandstead HH. 2000 Causes of iron and zinc deficiencies and their effects on brain. J Nutr 130, 347S–349S.
Sansi KAO, Pond WG. 1974 Pathology of dietary cadmium toxicity in growing rats and the protective effect of injected iron. Nutr Rep Int 9, 407–414.
Satarug S, Baker JR, Reilly PEB, Moore MR, Williams DJ. 2001 Changes in zinc and copper homeostasis in human livers and kidneys associated with exposure to environmental cadmium. Hum Exp Toxicol 20, 205–213.
SchÄfer SG, Forth W. 1984 Effect of acute and subchronic exposure to cadmium on the retention of iron in rats. J Nutr 114, 1989–1996.
SchÄfer SG, Elsenhans B. 1985 Iron retention and distribution in the cadmium-induced iron deficiency. Ecotoxicol Environ Safety 10, 128–141.
SchÄfer SG, Schwegler U, SchÜmann K. 1990 Retention of cadmium in cadmium-naive normal and iron-deficient rats as well as cadmium-induced iron-deficient animals. Ecotoxicol Environ Safety 20, 71–81
SchÜmann K, Elsenhans B, Maurer A. Iron supplementation. 1998 J Trace Elem Med Biol 12, 129–140.
Sonawane BR, Nordberg M, Nordberg GF, Lucier GW. 1975 Placental transfer of cadmium in rats: influence of dose and gestational age. Environ Health Perspect 12, 97–102.
Sorell TL, Graziano JH. 1990 Effect of oral cadmium exposure during pregnancy on maternal and fetal zinc metabolism in the rat. Toxicol Appl Pharmacol 102, 537–545.
Sugawara N, Sugawara C, Miyake H. 1984 Effects of subcutaneous and oral cadmium on iron metabolism: role of ceruloplasmin and metallothionein. Arch Toxicol 56, 25–28.
Sugawara N, Chen B-Q, Sugawara C, Miyake H. 1988 Effects of cadmium on Fe+3-transferrin formation in the rat intestinal mucosa. Bull Environ Contam Toxicol 41, 50–55.
Sugawara N, Sugawara C. 1991 Interactions of cadmium compounds with endogenous iron in the intestinal tract. Bull Environ Contam Toxicol 46, 263–270.
Tallkvist J, Bowlus CL, LÖnnerdal B. 2001 DMT1 gene expression and cadmium absorption in human absorptive enterocytes. Toxicol Lett 122, 171–177.
Tandon SK, Khandelwal S, Jain VK, Mathur N. 1993 Influence of dietary iron deficiency on acute metal intoxication. BioMetals 6, 133–138.
Tandon SK, Khandelwal S, Jain VK, Mathur N. 1994 Influence of dietary iron deficiency on nickel, lead and cadmium intoxication. Sci Total Environ 148, 167–173.
Trottier B, Athot J, Ricard A, Lafond J. 2002 Metal-fetal distribution of cadmium in the ginea pig following a low dose inhalation exposure. Toxicol Lett 129, 189–197.
Tsuchiya K. 1978 Cadmium Studies in Japan-A Review. Tokyo, Japan: Kodanasha Ltd.-Amsterdam, The Netherlands: Elsevier/North Holland Biomedical Press.
Valberg LS, Sorbie J, Hamilton DL. 1976 Gastrointestinal metabolism of cadmium in experimental iron deficiency. Am J Physiol 231: 462–467.
Whelton BD, Peterson DP, Moretti ES, Mauser RW, Bhattacharyya MH. 1997 Hepatic levels of cadmium, zinc and copper in multiparous, nulliparous and ovariectomized mice fed either a nutrient-sufficient or-deficient diet containing cadmium. Toxicology 119, 141–153.
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Piasek, M., Blanuša, M., Kostial, K. et al. Low iron diet and parenteral cadmium exposure in pregnant rats: the effects on trace elements and fetal viability. Biometals 17, 1–14 (2004). https://doi.org/10.1023/A:1024426931676
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DOI: https://doi.org/10.1023/A:1024426931676