The Impact of Perinatal Cobalt Chloride Exposure on Extramedullary Erythropoiesis, Tissue Iron Levels, and Transferrin Receptor Expression in Mice
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The objective of the present study was to elucidate the effect of perinatal cobalt chloride (CoCl2) exposure on extramedullary erythropoiesis in suckling mice in relation to iron (Fe) content and transferrin receptor (TfR) expression. Pregnant ICR mice were subjected to a daily dose of 75 mg CoCl2/kg body weight 2–3 days prior and 18 days after delivery. Co exposure significantly increased erythrocyte count (RBC), and reduced the erythrocytic parameters mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in the offspring. Total iron-binding capacity (TIBC) was decreased while bilirubin values were ~ 1.2-fold higher in the metal-exposed mice. Perinatal CoCl2 treatment also induced pathohistological changes in target organs (spleen, liver, and kidneys) as altered organ weight indices, leukocyte infiltration, abundant Kupffer cells in the liver, increased mesangial cellularity, and reduced capsular space in the kidney. CoCl2 administration induced significant 68-, 3.8-, 41.3-, and 162-fold increase of Co content in the kidney, spleen, liver, and RBC, respectively. Fe content in the target organs of CoCl2-treated mice was also significantly elevated. Immunohistochemical analysis demonstrated that TfR1 was well expressed in the renal tubules, hepatocytes, the red pulp, and marginal zone of white pulp in the spleen. TfR2 showed similar expression pattern, but its expression was stronger in the spleen and liver samples of Co-treated mice compared with that of the untreated controls. The results demonstrate that exposure to CoCl2 during late pregnancy and early postnatal period affects body and organ weights and alters hematological and biochemical parameters, iron content, and TfR expression in target organs.
KeywordsCobalt Iron Suckling mice Hematological indices TfR
The study was supported by Grant No. DNTS/Russia 02/1/14.06.2018 from the Bulgarian National Science Fund and No. 18-54-18006 from the Russian Foundation for Basic Research.
Compliance with Ethical Standards
This experimental design was carried out in accordance with the guidelines of EU Directive 2010/63/EU for animal experiments. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Conflict of Interest Statement
The authors declare that they have no conflict of interest.
- 5.Sipahi H, Eken A, Aydın A, Şahin G, Baydar T (2014) Safety assessment of essential and toxic metals in infant formulas. Turk J Pediatr 56:385–391Google Scholar
- 7.Muñoz-Sánchez J, Chánez-Cárdenas ME (2018) The use of cobalt chloride as a chemical hypoxia model. J Appl Toxicol. https://doi.org/10.1002/jat.3749
- 10.Millot S, Andrieu V, Letteron P, Lyoumi S, Hurtado-Nedelec M, Karim Z, Thibaudeau O, Bennada S, Charrier J-L, Lasocki S, Beaumont C (2010) Erythropoietin stimulates spleen BMP4-dependent stress erythropoiesis and partially corrects anemia in a mouse model of generalized inflammation. Blood 116:6072–6081CrossRefGoogle Scholar
- 12.Gluhcheva Y (2016) Transferrin receptors and hematopoiesis. Acta morphol anthropol 23:140–144Google Scholar
- 14.Skalny AV, Zaitseva IP, Gluhcheva YG, Skalny AA, Achkasov EE, Skalnaya MG, Tinkov AA (2018) Cobalt in athletes: hypoxia and doping – new crossroads. J Appl Biomed. https://doi.org/10.32725/jab.2018.003
- 15.Loréal O, Cavey T, Bardou-Jacquet E, Guggenbuhl P, Ropert M, Brissot P (2014) Iron, hepcidin, and the metal connection. Front Pharmacol 5:128Google Scholar
- 21.Kasvosve I, Delanghe J (2002) Total iron binding capacity and transferrin concentration in the assessment of iron status. Clin Chem Lab Med 40:1014–1018Google Scholar
- 22.Oyagbemi AA, Omobowale TO, Awoyomi OV, Ajibade TO, Falayi OO, Ogunpolu BS, Okotie UJ, Asenuga ER, Adejumobi OA, Hassan FO, Ola-Davies OE, Saba AB, Adedapo AA, Yakubu MA (2018) Cobalt chloride toxicity elicited hypertension and cardiac complication via induction of oxidative stress and upregulation of COX-2/Bax signaling pathway. Hum Exp Toxicol. https://doi.org/10.1177/0960327118812158
- 24.Awoyemi OV, Okotie UJ, Oyagbemi AA, Omobowale TO, Asenuga ER, Ola-Davies OE, Ogunpolu BS (2017) Cobalt chloride exposure dose-dependently induced hepatotoxicity through enhancement of cyclooxygenase-2 (COX-2)/B-cell associated protein X (BAX) signaling and genotoxicity in Wistar rats. Environ Toxicol 32:1899–1907CrossRefGoogle Scholar
- 25.Minior VK, Levine B, Ferber A, Guller S, Divon MY (2017) Nucleated red blood cells as a marker of acute and chronic fetal hypoxia in a rat model. Rambam Maimonides Med J. https://doi.org/10.5041/RMMJ.10302
- 26.Wolman M, Cervós-Navarro J, Sampaolo S, Cardesa A (1993) Pathological changes in organs of rats chronically exposed to hypoxia. Development of pulmonary lipidosis. Histol Histopathol 8:247–255Google Scholar
- 28.Chien CH, Hwu CM, Liou TL, Huang ZL, Shen AR, Yang VH, Lee CW, Chien EJ (2006) Inducible nitric oxide synthase expression and plasma bilirubin changes in rats under intermittent hypoxia treatment. Chin J Physiol 49:275–280Google Scholar
- 29.Losco P Mohr U, Dungworth DL (1992) Capen CC Normal development, growth, and aging of the spleen. Pathobiology of the aging rat. ILSI Press, Washington, DC, p 7594Google Scholar
- 41.Lu JP, Hayashi K, Awai M (1989) Transferrin receptor expression in normal, iron-deficient and iron-overloaded rats. Acta Pathol Jpn 39:759–764Google Scholar