Advertisement

Effect of Prepubertal Exposure to CdCl2 on the Liver, Hematological, and Biochemical Parameters in Female Rats; an Experimental Study

  • Saman Saedi
  • Mohammad Reza Jafarzadeh ShiraziEmail author
  • Mehdi Totonchi
  • Mohammad Javad Zamiri
  • Amin Derakhshanfar
Article
  • 8 Downloads

Abstract

The examination chemical factors including industrial toxins and heavy metals seem to be crucial during the prepubertal period. In order to investigate the effects of prepubertal exposure to toxic doses of Cd on liver, hematological, and biochemical parameters in the serum, 16 female rats weaned on postnatal day (PND) 21 were randomly divided into four groups with four rats in each (n = 4). The treatments were as follows: control (0.5 mL distilled water), 25, 50, and 75 mg/kg/day received cadmium chloride (CdCl2). The CdCl2 were administered orally from PND 21 days until observed first vaginal opening (VO). The result showed that the treatment of 75 mg/kg CdCl2 dramatically increased the serum level of LDL (P < 0.0001) and LDL/HDL ratio (P = 0.0004). Conversely, treatment of 75 mg/kg CdCl2 considerably decreased the serum level of HDL in comparison with control group (P = 0.0002). Nevertheless, the rats that received different doses of CdCl2 showed no significant differences in Glu, TG, and TC compared to control group. Number of RBC and Hb of rats treated with 75 mg/kg CdCl2 were significantly less than the other groups (P < 0.0001), whereas a number of WBCs in rats treated with 75 mg/kg CdCl2 (5.27 ± 0.13 103/μL) showed significant difference (P < 0.0001) compared to control group (4.23 ± 0.09 103/μL). Histopathological exams showed nodular accumulation of lymphocytes in the liver (lymphocytic hepatitis) of rats, treated with 75 mg/kg CdCl2. These results showed that CdCl2 could cause change in serum lipidome and hematological parameters. What is more, exposure to Cd triggers liver injury and cardiovascular disease during the prepubertal period.

Keywords

Cadmium Liver Lipid profile Hematological parameters Lymphocytic hepatitis 

Notes

Acknowledgments

The authors are grateful to members of the Center of Comparative and Experimental Medicine, Shiraz University of Medical Sciences, Shiraz.

Funding Information

The Shiraz University provided financial support.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interests.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

References

  1. 1.
    Agarwal S, Zaman T, Murat Tuzcu E, Kapadia SR (2011) Heavy metals and cardiovascular disease: results from the National Health and nutrition examination survey (NHANES) 1999-2006. Angiology 62:422–429CrossRefGoogle Scholar
  2. 2.
    Andjelkovic M, Buha Djordjevic A, Antonijevic E, Antonijevic B, Stanic M, Kotur-Stevuljevic J, Spasojevic-Kalimanovska V, Jovanovic M, Boricic N, Wallace D, Bulat Z (2019) Toxic effect of acute cadmium and Lead exposure in rat blood, liver, and kidney. Int J Environ Res Public Health 16:274CrossRefGoogle Scholar
  3. 3.
    Arroyo V, Flores K, Ortiz L et al (2012) Liver and cadmium toxicity. J Drug Metab Toxicol S 5Google Scholar
  4. 4.
    Atsdr S (2012) Toxicological profile for chromium. Agency for Toxic Substances and Disease Registry. Public Health Service, US Department of Health and Human Services. http://www.atsdr.cdc.gov/toxprofiles/tp.asp
  5. 5.
    Badisa VL, Latinwo LM, Odewumi CO et al (2007) Mechanism of DNA damage by cadmium and interplay of antioxidant enzymes and agents. Environmental Toxicology: An International Journal 22:144–151CrossRefGoogle Scholar
  6. 6.
    Bhattacharyya M (2000) Biochemical pathways in cadmium toxicity. Molecular biology and toxicology of metals:34–74Google Scholar
  7. 7.
    Bizoń A, Milnerowicz H (2017) The effect of passive and active exposure to tobacco smoke on lipid profile parameters and the activity of certain membrane enzymes in the blood of women in the first trimester of pregnancy. Environ Toxicol Pharmacol 53:74–80CrossRefGoogle Scholar
  8. 8.
    Brzóska MM (2012) Low-level chronic exposure to cadmium enhances the risk of long bone fractures: a study on a female rat model of human lifetime exposure. J Appl Toxicol 32:34–44CrossRefGoogle Scholar
  9. 9.
    Brzóska MM, Galażyn-Sidorczuk M, Dzwilewska I (2013) Ethanol consumption modifies the body turnover of cadmium: a study in a rat model of human exposure. J Appl Toxicol 33:784–798CrossRefGoogle Scholar
  10. 10.
    Chapatwala K, Hobson M, Desaiah D et al (1982) Effect of cadmium on hepatic and renal gluconeogenic enzymes in female rats. Toxicol Lett 12:27–34CrossRefGoogle Scholar
  11. 11.
    Chapatwala K, Rajanna E, Desaiah D (1980) Cadmium induced changes in gluconeogenic enzymes in rat kidney and liver. Drug Chem Toxicol 3:407–420CrossRefGoogle Scholar
  12. 12.
    Chen JP (2012) Decontamination of heavy metals: processes, mechanisms, and applications. Crc PressGoogle Scholar
  13. 13.
    Ding D, Li X, Qiu J et al. (2014) Serum lipids, apolipoproteins, and mortality among coronary artery disease patients. BioMed research international 2014Google Scholar
  14. 14.
    Duffus JH (2002) " heavy metals" a meaningless term? (IUPAC technical report). Pure Appl Chem 74:793–807CrossRefGoogle Scholar
  15. 15.
    El-Boshy ME, Risha EF, Abdelhamid FM et al (2015) Protective effects of selenium against cadmium induced hematological disturbances, immunosuppressive, oxidative stress and hepatorenal damage in rats. J Trace Elem Med Biol 29:104–110CrossRefGoogle Scholar
  16. 16.
    Enomoto M, Adachi H, Hirai Y et al (2011) LDL-C/HDL-C ratio predicts carotid intima-media thickness progression better than HDL-C or LDL-C alone. J Lipids:2011Google Scholar
  17. 17.
    Ferraro PM, Costanzi S, Naticchia A, Sturniolo A, Gambaro G (2010) Low level exposure to cadmium increases the risk of chronic kidney disease: analysis of the NHANES 1999-2006. BMC Public Health 10:304CrossRefGoogle Scholar
  18. 18.
    Franssen D, Ioannou YS, Alvarez-Real A et al (2014) Pubertal timing after neonatal diethylstilbestrol exposure in female rats: neuroendocrine vs peripheral effects and additive role of prenatal food restriction. Reprod Toxicol 44:63–72CrossRefGoogle Scholar
  19. 19.
    Gadelha ICN, Fernandes De Macedo M, Oloris SCS et al (2014) Gossypol promotes degeneration of ovarian follicles in rats. Sci World J:2014Google Scholar
  20. 20.
    Giesbrecht GF, Ejaredar M, Liu J et al (2017) Prenatal bisphenol a exposure and dysregulation of infant hypothalamic-pituitary-adrenal axis function: findings from the APrON cohort study. Environ Health 16:47CrossRefGoogle Scholar
  21. 21.
    Gill TS, Epple A (1993) Stress-related changes in the hematological profile of the American eel (Anguilla rostrata). Ecotoxicol Environ Saf 25:227–235CrossRefGoogle Scholar
  22. 22.
    Go Y-M, Sutliff RL, Chandler JD, Khalidur R, Kang BY, Anania FA, Orr M, Hao L, Fowler BA, Jones DP (2015) Low-dose cadmium causes metabolic and genetic dysregulation associated with fatty liver disease in mice. Toxicol Sci 147:524–534CrossRefGoogle Scholar
  23. 23.
    Graczyk A, Radomska K, Dlugaszek M (2000) Synergizm i antagonizm miedzy biopierwiastkami i metalami toksycznymi. Ochrona Środowiska i Zasobów Naturalnych:39–45Google Scholar
  24. 24.
    Hambach R, Lison D, D’haese P et al (2013) Co-exposure to lead increases the renal response to low levels of cadmium in metallurgy workers. Toxicol Lett 222:233–238CrossRefGoogle Scholar
  25. 25.
    Han X, He Y, Zeng G, Wang Y, Sun W, Liu J, Sun Y, Yu J (2017) Intracerebroventricular injection of RFRP-3 delays puberty onset and stimulates growth hormone secretion in female rats. Reprod Biol Endocrinol 15:35CrossRefGoogle Scholar
  26. 26.
    Hoshyari E, Pourkhabbaz A, Mansouri B (2012) Contaminations of metal in tissues of Siberian gull Larusheuglini: gender, age, and tissue differences. Bull Environ Contam Toxicol 89:102–106CrossRefGoogle Scholar
  27. 27.
    Hounkpatin A, Edorh P, Guédénon P et al (2013) Haematological evaluation of Wistar rats exposed to chronic doses of cadmium, mercury and combined cadmium and mercury. Afr J Biotechnol 12Google Scholar
  28. 28.
    Ibraheem AS, Seleem AA, El-Sayed MF et al (2016) Single or combined cadmium and aluminum intoxication of mice liver and kidney with possible effect of zinc. The Journal of Basic & Applied Zoology 77:91–101CrossRefGoogle Scholar
  29. 29.
    Ibrahim MA, Almaeen AH, El Moneim MA et al (2018) Cadmium-induced hematological, renal, and hepatic toxicity: the amelioration by spirulina platensis. The Saudi Journal of Forensic Medicine and Sciences 1:5CrossRefGoogle Scholar
  30. 30.
    Järup L (2003) Hazards of heavy metal contamination. Br Med Bull 68:167–182CrossRefGoogle Scholar
  31. 31.
    Jung U, Choi M-S (2014) Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci 15:6184–6223CrossRefGoogle Scholar
  32. 32.
    Jurczuk M, Brzóska MM, Moniuszko-Jakoniuk J et al (2004) Antioxidant enzymes activity and lipid peroxidation in liver and kidney of rats exposed to cadmium and ethanol. Food Chem Toxicol 42:429–438CrossRefGoogle Scholar
  33. 33.
    Jurczuk M, Moniuszko-Jakoniuk J, Brzóska M et al (2003) Superoxidase dismutase and catalase activities and malondialdehyde concentration in the brain rats co-exposed to lead or cadmium and ethanol. Pol J Environ Stud 12:199–203Google Scholar
  34. 34.
    Kinouchi R, Matsuzaki T, Iwasa T, Gereltsetseg G, Nakazawa H, Kunimi K, Kuwahara A, Yasui T, Irahara M (2012) Prepubertal exposure to glucocorticoid delays puberty independent of the hypothalamic Kiss1-GnRH system in female rats. Int J Dev Neurosci 30:596–601CrossRefGoogle Scholar
  35. 35.
    Kojima M, Masui T, Nemoto K, Degawa M (2004) Lead nitrate-induced development of hypercholesterolemia in rats: sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis. Toxicol Lett 154:35–44CrossRefGoogle Scholar
  36. 36.
    Kucuk A, Uslu AU, Icli A et al (2017) The LDL/HDL ratio and atherosclerosis in ankylosing spondylitis. Z Rheumatol 76:58–63CrossRefGoogle Scholar
  37. 37.
    Larregle EV, Varas SM, Oliveros LB, Martinez LD, Antón R, Marchevsky E, Giménez MS (2008) Lipid metabolism in liver of rat exposed to cadmium. Food Chem Toxicol 46:1786–1792CrossRefGoogle Scholar
  38. 38.
    Liju VB, Jeena K, Kuttan R (2013) Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L). Food Chem Toxicol 53:52–61CrossRefGoogle Scholar
  39. 39.
    Lucia M, André J-M, Gonzalez P, Baudrimont M, Bernadet MD, Gontier K, Maury-Brachet R, Guy G, Davail S (2010) Effect of dietary cadmium on lipid metabolism and storage of aquatic bird Cairina moschata. Ecotoxicology 19:163–170CrossRefGoogle Scholar
  40. 40.
    Marcondes F, Bianchi F, Tanno A (2002) Determination of the estrous cycle phases of rats: some helpful considerations. Braz J Biol 62:609–614CrossRefGoogle Scholar
  41. 41.
    Mehbub M, Lei J, Franco C, Zhang W (2014) Marine sponge derived natural products between 2001 and 2010: trends and opportunities for discovery of bioactives. Marine drugs 12:4539–4577CrossRefGoogle Scholar
  42. 42.
    Menke A, Muntner P, Silbergeld EK et al (2008) Cadmium levels in urine and mortality among US adults. Environ Health Perspect 117:190–196CrossRefGoogle Scholar
  43. 43.
    Murugavel P, Pari L (2007) Diallyl tetrasulfide protects cadmium-induced alterations in lipids and plasma lipoproteins in rats. Nutr Res 27:356–361CrossRefGoogle Scholar
  44. 44.
    Ng DS (2013) Lecithin cholesterol acyltransferase deficiency protects from diet-induced insulin resistance and obesity—novel insights from mouse models. Vitamins & Hormones, Elsevier, pp 259–270Google Scholar
  45. 45.
    Ojeda SR, Skinner MK (2006) Puberty in the rat. In: Knobil and Neill's physiology of reproduction. Elsevier IncGoogle Scholar
  46. 46.
    Olisekodiaka M, Igbeneghu C, Onuegbu A et al (2012) Lipid, lipoproteins, total antioxidant status and organ changes in rats administered high doses of cadmium chloride. Med Princ Pract 21:156–159CrossRefGoogle Scholar
  47. 47.
    Pamir N, Hutchins P, Ronsein G, Vaisar T, Reardon CA, Getz GS, Lusis AJ, Heinecke JW (2016) Proteomic analysis of HDL from inbred mouse strains implicates APOE associated with HDL in reduced cholesterol efflux capacity via the ABCA1 pathway. J Lipid Res 57:246–257CrossRefGoogle Scholar
  48. 48.
    Parasuraman S, Raveendran R, Kesavan R (2010) Blood sample collection in small laboratory animals. J Pharmacol Pharmacother 1:87CrossRefGoogle Scholar
  49. 49.
    Ramaiah L, Bounous DI, Elmore SA (2013) Hematopoietic system. In: Haschek and Rousseaux's handbook of Toxicologic pathology. Elsevier, Third Edition, pp 1863–1933CrossRefGoogle Scholar
  50. 50.
    Ramirez DC, Gimenez MS (2002) Lipid modification in mouse peritoneal macrophages after chronic cadmium exposure. Toxicology 172:1–12CrossRefGoogle Scholar
  51. 51.
    Rogalska J, Brzóska MM, Roszczenko A, Moniuszko-Jakoniuk J (2009) Enhanced zinc consumption prevents cadmium-induced alterations in lipid metabolism in male rats. Chem Biol Interact 177:142–152CrossRefGoogle Scholar
  52. 52.
    Samarghandian S, Azimi-Nezhad M, Shabestari MM, Azad FJ, Farkhondeh T, Bafandeh F (2015) Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative stress indices in male rats. Interdiscip Toxicol 8:151–154CrossRefGoogle Scholar
  53. 53.
    Sarmiento-Ortega VE, Treviño S, Flores-Hernández JÁ, Aguilar-Alonso P, Moroni-González D, Aburto-Luna V, Diaz A, Brambila E (2017) Changes on serum and hepatic lipidome after a chronic cadmium exposure in Wistar rats. Arch Biochem Biophys 635:52–59CrossRefGoogle Scholar
  54. 54.
    Satarug S, Baker JR, Urbenjapol S, Haswell-Elkins M, Reilly PEB, Williams DJ, Moore MR (2003) A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicol Lett 137:65–83CrossRefGoogle Scholar
  55. 55.
    Schwartz GG, Il’yasova D, Ivanova A (2003) Urinary cadmium, impaired fasting glucose, and diabetes in the NHANES III. Diabetes Care 26:468–470CrossRefGoogle Scholar
  56. 56.
    Smyth CE, Knee R, Wilkinson M, Murphy PR (1997) Decline in basic fibroblast growth factor (FGF-2) mRNA expression in female rat hypothalamus at puberty. J Neuroendocrinol 9:151–159CrossRefGoogle Scholar
  57. 57.
    Syers J, Gochfeld M (2000) Environmental cadmium in the food chain: sources, pathways, and risks. In: Proceedings of the SCOPE Workshop, Brussels. p 13–16Google Scholar
  58. 58.
    Takiguchi M, Yoshihara SI (2006) New aspects of cadmium as endocrine disruptor. Environmental Sciences: an international journal of environmental physiology and toxicology 13:107–116Google Scholar
  59. 59.
    Tellez-Plaza M, Navas-Acien A, Menke A, Crainiceanu CM, Pastor-Barriuso R, Guallar E (2012) Cadmium exposure and all-cause and cardiovascular mortality in the US general population. Environ Health Perspect 120:1017–1022CrossRefGoogle Scholar
  60. 60.
    Tinkov AA, Filippini T, Ajsuvakova OP et al (2017) The role of cadmium in obesity and diabetes. Sci Total Environ 601:741–755CrossRefGoogle Scholar
  61. 61.
    Tomaszewska E, Dobrowolski P, Winiarska-Mieczan A, Kwiecień M, Tomczyk A, Muszyński S (2017) The effect of tannic acid on the bone tissue of adult male Wistar rats exposed to cadmium and lead. Exp Toxicol Pathol 69:131–141CrossRefGoogle Scholar
  62. 62.
    Toth D, Wonger H (2003) Clinical chemistry textbook. Oxford University Press, OxfordGoogle Scholar
  63. 63.
    Umemura T (2000) Experimental reproduction of itai-itai disease, a chronic cadmium poisoning of humans, in rats and monkeys. Jpn J Vet Res 48:15–28Google Scholar
  64. 64.
    Winiarska-Mieczan A (2013) Protective effect of tannic acid on the brain of adult rats exposed to cadmium and lead. Environ Toxicol Pharmacol 36:9–18CrossRefGoogle Scholar
  65. 65.
    Yamano T, Shimizu M, Noda T (1998) Comparative effects of repeated administration of cadmium on kidney, spleen, thymus, and bone marrow in 2-, 4-, and 8-month-old male Wistar rats. Toxicol Sci 46:393–402CrossRefGoogle Scholar
  66. 66.
    Yang R, Wang Y-M, Zhang L-S, Zhang L, Zhao ZM, Zhao J, Peng SQ (2015) Delay of the onset of puberty in female rats by prepubertal exposure to T-2 toxin. Toxins 7:4668–4683CrossRefGoogle Scholar
  67. 67.
    Yang R, Wang Y, Zhang L et al (2016) Prepubertal exposure to T-2 toxin advances pubertal onset and development in female rats via promoting the onset of hypothalamic–pituitary–gonadal axis function. Hum Exp Toxicol 35:1276–1285CrossRefGoogle Scholar
  68. 68.
    Yildirim S, Celikezen FC, Oto G, Sengul E, Bulduk M, Tasdemir M, Ali Cinar D (2018) An investigation of protective effects of litium borate on blood and histopathological parameters in acute cadmium-induced rats. Biol Trace Elem Res 182:287–294CrossRefGoogle Scholar
  69. 69.
    Yuan G, Dai S, Yin Z et al (2014) Toxicological assessment of combined lead and cadmium: acute and sub-chronic toxicity study in rats. Food Chem Toxicol 65:260–268CrossRefGoogle Scholar
  70. 70.
    Yuhas E, Miya T, Schnell R (1979) Dose-related alterations in growth and mineral disposition by chronic oral cadmium administration in the male rat. Toxicology 12:19–29CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Animal Science, College of AgricultureShiraz UniversityShirazIran
  2. 2.Department of GeneticsRoyan Institute for Reproductive Biomedicine, ACECRTehranIran
  3. 3.Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical SciencesShiraz University of Medical SciencesShirazIran
  4. 4.Center of Comparative and Experimental MedicineShiraz University of Medical SciencesShirazIran

Personalised recommendations