{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T18:54:24Z","timestamp":1779216864326,"version":"3.51.4"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005632","name":"Narodowe Centrum Bada\u0144 i Rozwoju","doi-asserted-by":"publisher","award":["LIDER\/37\/0133\/L-11\/19\/NCBR\/2020"],"award-info":[{"award-number":["LIDER\/37\/0133\/L-11\/19\/NCBR\/2020"]}],"id":[{"id":"10.13039\/501100005632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharmacol. Rep"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Recombinant granulocyte colony-stimulating factor (G-CSF) is the most commonly used agent for treating neutropenia and mobilizing hematopoietic stem cells (HSCs) for transplantation. However, some patients do not respond effectively to the currently used mobilization protocols. To address this, new therapeutic approaches are needed. A potential strategy is pharmacological induction of endogenous mobilizing factors via cobalt protoporphyrin IX (CoPP). CoPP mobilizes HSCs and granulocytes by increasing endogenous G-CSF, though optimal dosing and potential side effects remain unclear. Our study aimed to optimize CoPP dosing and timing, and assess its safety in mobilizing cells from bone marrow to blood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Mice were treated with different doses of CoPP, and blood cell counts, cytokine concentrations, and organ damage markers were evaluated at various time points after injection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Our results show that CoPP exerts a dose-dependent mobilizing effect, with the highest G-CSF levels and number of mobilized leukocytes observed in mice treated with 10\u00a0mg\/kg of CoPP. While there were no severe adverse effects, there were mild fluctuations in markers of organ function, including a reduction in blood urea nitrogen (BUN) and glucose levels during the five days of administration. Additionally, although most parameters normalized within 30 days, the decrease in BUN persisted. Mice experienced short-term weight loss following CoPP administration, but they regained their initial weight within two weeks.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This study demonstrates that CoPP mobilizes cells from the bone marrow to the blood in a dose-dependent manner, with mild side effects, including temporary changes in biochemical markers and a sustained reduction in BUN levels.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s43440-025-00751-4","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:20:48Z","timestamp":1752139248000},"page":"1295-1308","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cobalt protoporphyrin IX induces transient, dose- and time-dependent granulocyte mobilization with mild metabolic effects in mice"],"prefix":"10.1007","volume":"77","author":[{"given":"Aleksandra","family":"Bednarz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"Ko\u017cuch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kacper","family":"Kowalski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7620-6089","authenticated-orcid":false,"given":"Izabella","family":"Skulimowska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3226-0726","authenticated-orcid":false,"given":"Neli","family":"Kachamakova-Trojanowska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jadwiga","family":"Filipek-Gorza\u0142a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2632-4025","authenticated-orcid":false,"given":"Patrycja","family":"Kwieci\u0144ska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7015-154X","authenticated-orcid":false,"given":"Kinga","family":"Gawli\u0144ska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kinga","family":"Male\u017cyna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"Kubiak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Bryniarska-Kubiak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7317-260X","authenticated-orcid":false,"given":"Alicja","family":"J\u00f3zkowicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7227-4276","authenticated-orcid":false,"given":"Krzysztof","family":"Szade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0575-4659","authenticated-orcid":false,"given":"Agata","family":"Szade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"751_CR1","doi-asserted-by":"crossref","unstructured":"Tenhunen R, Marver HS, Schmid R. The enzymatic conversion of Heme to bilirubin by microsomal Heme Oxygenase. Proc Natl Acad Sci U S A. 1968;61:748\u201355.","DOI":"10.1073\/pnas.61.2.748"},{"key":"751_CR2","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1021\/bi00804a016","volume":"9","author":"R Tenhunen","year":"1970","unstructured":"Tenhunen R, Ross ME, Marver HS, Schmid R. Reduced nicotinamide adenine dinucleotide phosphate dependent biliverdin reductase. Partial purification and characterization. Biochemistry. 1970;9:298\u2013303.","journal-title":"Biochemistry"},{"key":"751_CR3","first-page":"247","volume-title":"Suppression and regulation of immune responses: methods and protocols","author":"P Blancou","year":"2011","unstructured":"Blancou P, Tardif V, Simon T, R\u00e9my S, Carre\u00f1o L, Kalergis A, et al. Immunoregulatory properties of Heme oxygenase-1. In: Cuturi MC, Anegon I, editors. Suppression and regulation of immune responses: methods and protocols. Totowa, NJ: Humana; 2011. pp. 247\u201368."},{"key":"751_CR4","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/74680","volume":"6","author":"LE Otterbein","year":"2000","unstructured":"Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med. 2000;6:422\u20138.","journal-title":"Nat Med"},{"key":"751_CR5","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/nm0302-240","volume":"8","author":"TS Lee","year":"2002","unstructured":"Lee TS, Chau LY. Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med. 2002;8:240\u20136.","journal-title":"Nat Med"},{"key":"751_CR6","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1089\/ars.2008.2043","volume":"10","author":"A Loboda","year":"2008","unstructured":"Loboda A, Jazwa A, Grochot-Przeczek A, Rutkowski AJ, Cisowski J, Agarwal A, et al. Heme oxygenase-1 and the vascular bed: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. 2008;10:1767\u2013812.","journal-title":"Antioxid Redox Signal"},{"key":"751_CR7","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1152\/physrev.00011.2005","volume":"86","author":"SW Ryter","year":"2006","unstructured":"Ryter SW, Alam J, Choi AMK. Heme oxygenase-1\/carbon monoxide: from basic science to therapeutic applications. Physiol Rev. 2006;86:583\u2013650.","journal-title":"Physiol Rev"},{"key":"751_CR8","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1096\/fj.04-3259com","volume":"19","author":"SB Blumenthal","year":"2005","unstructured":"Blumenthal SB, Kiemer AK, Tiegs G, Seyfried S, H\u00f6ltje M, Brandt B, et al. Metalloporphyrins inactivate caspase-3 and\u2013\u20098. FASEB J. 2005;19:1272\u20139.","journal-title":"FASEB J"},{"key":"751_CR9","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.cbi.2009.01.004","volume":"180","author":"HY Lin","year":"2009","unstructured":"Lin HY, Shen SC, Lin CW, Wu MS, Chen YC. Cobalt protoporphyrin Inhibition of lipopolysaccharide or Lipoteichoic acid-induced nitric oxide production via blocking c-Jun N-terminal kinase activation and nitric oxide enzyme activity. Chem Biol Interact. 2009;180:202\u201310.","journal-title":"Chem Biol Interact"},{"issue":"7","key":"751_CR10","doi-asserted-by":"publisher","first-page":"4497","DOI":"10.1007\/s12035-015-9376-y","volume":"53","author":"HY Lin","year":"2016","unstructured":"Lin HY, Tsai CH, Lin C, Yeh WL, Tsai CF, Chang PC, et al. Cobalt protoporphyrin upregulates Cyclooxygenase-2 expression through a Heme Oxygenase-Independent mechanism. Mol Neurobiol. 2016;53(7):4497\u2013508.","journal-title":"Mol Neurobiol"},{"key":"751_CR11","doi-asserted-by":"publisher","first-page":"e09571","DOI":"10.15252\/emmm.201809571","volume":"11","author":"A Szade","year":"2019","unstructured":"Szade A, Szade K, Nowak WN, Bukowska-Strakova K, Muchova L, Go\u0144ka M, et al. Cobalt protoporphyrin IX increases endogenous G-CSF and mobilizes HSC and granulocytes to the blood. EMBO Mol Med. 2019;11:e09571.","journal-title":"EMBO Mol Med"},{"key":"751_CR12","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1182\/blood.V78.4.975.975","volume":"78","author":"L Weiss","year":"1991","unstructured":"Weiss L, Geduldig U. Barrier cells: stromal regulation of hematopoiesis and blood cell release in normal and stressed murine bone marrow. Blood. 1991;78:975\u201390.","journal-title":"Blood"},{"key":"751_CR13","doi-asserted-by":"crossref","unstructured":"Lapid K, Glait-Santar C, Gur-Cohen S, Canaani J, Kollet O, Lapidot T. In: StemBook, editor. Egress and mobilization of hematopoietic stem and progenitor cells: a dynamic multi-facet process. Cambridge (MA): Harvard Stem Cell Institute; 2008.","DOI":"10.3824\/stembook.1.39.1"},{"key":"751_CR14","doi-asserted-by":"publisher","first-page":"102427","DOI":"10.1016\/j.ctrv.2022.102427","volume":"109","author":"DW Blayney","year":"2022","unstructured":"Blayney DW, Schwartzberg L. Chemotherapy-induced neutropenia and emerging agents for prevention and treatment: A review. Cancer Treat Rev. 2022;109:102427.","journal-title":"Cancer Treat Rev"},{"key":"751_CR15","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1186\/s13287-021-02379-6","volume":"12","author":"C Luo","year":"2021","unstructured":"Luo C, Wang L, Wu G, Huang X, Zhang Y, Ma Y, et al. Comparison of the efficacy of hematopoietic stem cell mobilization regimens: a systematic review and network meta-analysis of preclinical studies. Stem Cell Res Ther. 2021;12:310.","journal-title":"Stem Cell Res Ther"},{"key":"751_CR16","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1007\/s12015-021-10272-1","volume":"17","author":"JB Menendez-Gonzalez","year":"2021","unstructured":"Menendez-Gonzalez JB, Hoggatt J. Hematopoietic stem cell mobilization: current collection approaches, stem cell heterogeneity, and a proposed new method for stem cell transplant conditioning. Stem Cell Rev Rep. 2021;17:1939\u201353.","journal-title":"Stem Cell Rev Rep"},{"key":"751_CR17","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.cytogfr.2014.07.011","volume":"25","author":"LJ Bendall","year":"2014","unstructured":"Bendall LJ, Bradstock KF. G-CSF: from granulopoietic stimulant to bone marrow stem cell mobilizing agent. Cytokine Growth Factor Rev. 2014;25:355\u201367.","journal-title":"Cytokine Growth Factor Rev"},{"key":"751_CR18","doi-asserted-by":"publisher","first-page":"4530","DOI":"10.1182\/blood-2011-06-318220","volume":"118","author":"LB To","year":"2011","unstructured":"To LB, Levesque JP, Herbert KE. How I treat patients who mobilize hematopoietic stem cells poorly. Blood. 2011;118:4530\u201340.","journal-title":"Blood"},{"key":"751_CR19","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1517\/13543784.2013.838558","volume":"23","author":"J Hoggatt","year":"2014","unstructured":"Hoggatt J, Pelus LM. New G-CSF agonists for neutropenia therapy. Expert Opin Investig Drugs. 2014;23:21\u201335.","journal-title":"Expert Opin Investig Drugs"},{"key":"751_CR20","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1038\/s41409-022-01789-1","volume":"57","author":"P Kuang","year":"2022","unstructured":"Kuang P, Lin T, Chen X, Yang Y, Ji J, Dong T, et al. Plerixafor as a preemptive or salvage therapy for healthy donors with poor mobilization of hematopoietic stem cells. Bone Marrow Transpl. 2022;57:1737\u20139.","journal-title":"Bone Marrow Transpl"},{"key":"751_CR21","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3324\/haematol.2015.136630","volume":"101","author":"RP Gazendam","year":"2016","unstructured":"Gazendam RP, van de Geer A, van Hamme JL, Tool ATJ, van Rees DJ, Aarts CEM, et al. Impaired killing of Candida albicans by granulocytes mobilized for transfusion purposes: a role for granule components. Haematologica. 2016;101:587\u201396.","journal-title":"Haematologica"},{"key":"751_CR22","doi-asserted-by":"crossref","unstructured":"M\u00fcller AMS, Linderman JA, Florek M, Miklos D, Shizuru JA. Allogeneic T cells impair engraftment and hematopoiesis after stem cell transplantation. Proc. Natl. Acad. Sci. 2010;107:14721\u20136.","DOI":"10.1073\/pnas.1009220107"},{"key":"751_CR23","doi-asserted-by":"publisher","first-page":"4103","DOI":"10.1016\/0006-2952(89)90692-8","volume":"38","author":"BB Muhoberac","year":"1989","unstructured":"Muhoberac BB, Hanew T, Halter S, Schenker S. A model of cytochrome P-450-centered hepatic dysfunction in drug metabolism induced by cobalt-protoporphyrin administration. Biochem Pharmacol. 1989;38:4103\u201313.","journal-title":"Biochem Pharmacol"},{"key":"751_CR24","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1016\/S0140-6736(02)11203-7","volume":"360","author":"DW Nebert","year":"2002","unstructured":"Nebert DW, Russell DW. Clinical importance of the cytochromes P450. The Lancet. 2002;360:1155\u201362.","journal-title":"Lancet"},{"key":"751_CR25","doi-asserted-by":"publisher","first-page":"846","DOI":"10.3390\/pharmaceutics12090846","volume":"12","author":"M Deodhar","year":"2020","unstructured":"Deodhar M, Al Rihani SB, Arwood MJ, Darakjian L, Dow P, Turgeon J, et al. Mechanisms of CYP450 inhibition: Understanding Drug-Drug interactions due to Mechanism-Based Inhibition in clinical practice. Pharmaceutics. 2020;12:846.","journal-title":"Pharmaceutics"},{"key":"751_CR26","first-page":"4567","volume":"17","author":"J Li","year":"2018","unstructured":"Li J, Wu B, Teng D, Sun X, Li J, Li J, et al. Cobalt-protoporphyrin enhances Heme Oxygenase 1 expression and attenuates liver ischemia\/reperfusion injury by inhibiting apoptosis. Mol Med Rep. 2018;17:4567\u201372.","journal-title":"Mol Med Rep"},{"key":"751_CR27","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s10020-022-00499-0","volume":"28","author":"PH Fang","year":"2022","unstructured":"Fang PH, Lai YY, Chen CL, Wang HY, Chang YN, Lin YC, et al. Cobalt protoporphyrin promotes human keratinocyte migration under hyperglycemic conditions. Mol Med. 2022;28:71.","journal-title":"Mol Med"},{"key":"751_CR28","doi-asserted-by":"publisher","first-page":"3757","DOI":"10.1182\/blood-2009-04-218651","volume":"114","author":"K H\u00f6lig","year":"2009","unstructured":"H\u00f6lig K, Kramer M, Kroschinsky F, Bornh\u00e4user M, Mengling T, Schmidt AH, et al. Safety and efficacy of hematopoietic stem cell collection from mobilized peripheral blood in unrelated volunteers: 12 years of single-center experience in 3928 donors. Blood. 2009;114:3757\u201363.","journal-title":"Blood"},{"key":"751_CR29","doi-asserted-by":"publisher","first-page":"238","DOI":"10.3109\/02713683.2010.539760","volume":"36","author":"PH Peng","year":"2011","unstructured":"Peng PH, Chao HM, Juan SH, Chen CF, Liu JH, Ko ML. Pharmacological preconditioning by low dose Cobalt protoporphyrin induces Heme Oxygenase-1 overexpression and alleviates retinal Ischemia-Reperfusion injury in rats. Curr Eye Res. 2011;36:238\u201346.","journal-title":"Curr Eye Res"},{"key":"751_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.trim.2010.08.002","volume":"24","author":"F Besenzon","year":"2010","unstructured":"Besenzon F, Dedja A, Vadori M, Bosio E, Seveso M, Tognato Ei in. In vitro and in vivo Immunomodulatory effects of Cobalt protoporphyrin administered in combination with immunosuppressive drugs. Transpl Immunol. 2010;24:1\u20138.","journal-title":"Transpl Immunol"},{"key":"751_CR31","doi-asserted-by":"crossref","unstructured":"Lin KK, Goodell MA. Detection of hematopoietic stem cells by flow cytometry. In: Darzynkiewicz Z, Holden E, Orfao A, Telford W, Wlodkowic D, editors. Methods in cell biology. Academic; 2011. pp. 21\u201330.","DOI":"10.1016\/B978-0-12-385493-3.00002-4"},{"key":"751_CR32","first-page":"244","volume":"36","author":"E Csongradi","year":"2012","unstructured":"Csongradi E, Docarmo JM, Dubinion JH, Vera T, Stec DE. Chronic HO-1 induction with Cobalt protoporphyrin (CoPP) treatment increases oxygen consumption, activity, heat production and lowers body weight in obese melanocortin-4 receptor-deficient mice. Int J Obes 2005. 2012;36:244\u201353.","journal-title":"Int J Obes 2005"},{"key":"751_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1542\/peds.103.1.1","volume":"103","author":"JC Martinez","year":"1999","unstructured":"Martinez JC, Garcia HO, Otheguy LE, Drummond GS, Kappas A. Control of severe hyperbilirubinemia in full-term newborns with the inhibitor of bilirubin production Sn-mesoporphyrin. Pediatrics. 1999;103:1\u20135.","journal-title":"Pediatrics"},{"key":"751_CR34","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1542\/peds.108.1.25","volume":"108","author":"A Kappas","year":"2001","unstructured":"Kappas A, Drummond GS, Valaes T. A single dose of Sn-mesoporphyrin prevents development of severe hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient newborns. Pediatrics. 2001;108:25\u201330.","journal-title":"Pediatrics"},{"key":"751_CR35","doi-asserted-by":"crossref","unstructured":"Lamy A, Chertow GM, Jessen M, Collar A, Brown CD, Mack CA et al. Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. eClinicalMedicine. 2024;68.","DOI":"10.1016\/j.eclinm.2023.102364"},{"key":"751_CR36","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.urology.2007.11.123","volume":"72","author":"T Iwai","year":"2008","unstructured":"Iwai T, Kitamoto K, Teramoto K, Machida Y, Tamada S, Yukimura T, et al. Cobalt protoporphyrin attenuates rat obstructive nephropathy: role of cellular infiltration. Urology. 2008;72:432\u20138.","journal-title":"Urology"},{"key":"751_CR37","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1007\/s10534-015-9861-9","volume":"28","author":"Y Yashima","year":"2015","unstructured":"Yashima Y, Okamoto K, Sakai E, Iwatake M, Fukuma Y, Nishishita K, et al. Cobalt protoporphyrin represses osteoclastogenesis through blocking multiple signaling pathways. Biometals. 2015;28:725\u201332.","journal-title":"Biometals"},{"key":"751_CR38","first-page":"1983","volume":"100","author":"M Li","year":"2006","unstructured":"Li M, Vizzard MA, Jaworski DM, Galbraith RA. The weight loss elicited by Cobalt protoporphyrin is related to decreased activity of nitric oxide synthase in the hypothalamus. J Appl Physiol Bethesda Md 1985. 2006;100:1983\u201391.","journal-title":"J Appl Physiol Bethesda Md 1985"},{"key":"751_CR39","doi-asserted-by":"publisher","first-page":"2690","DOI":"10.3390\/ani13172690","volume":"13","author":"L Li","year":"2023","unstructured":"Li L, Hu X, Li S, Li Y, Zhao S, Shen F, et al. Cobalt protoporphyrin blocks EqHV-8 infection via IFN-\u03b1\/\u03b2 production. Animals. 2023;13:2690.","journal-title":"Animals"},{"key":"751_CR40","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1038\/s41423-022-00887-w","volume":"19","author":"S Zhang","year":"2022","unstructured":"Zhang S, Wang J, Wang L, Aliyari S, Cheng G. SARS-CoV-2 virus NSP14 impairs NRF2\/HMOX1 activation by targeting Sirtuin 1. Cell Mol Immunol. 2022;19:872\u201382.","journal-title":"Cell Mol Immunol"},{"key":"751_CR41","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/S0006-8993(96)00423-4","volume":"729","author":"SJ Choi","year":"1996","unstructured":"Choi SJ, Meeran K, O\u2019Shea D, Lambert PD, Bloom SR. Weight loss in rats treated with intracerebroventricular Cobalt protoporphyrin is not specific to the neuropeptide Y system. Brain Res. 1996;729:223\u20137.","journal-title":"Brain Res"},{"key":"751_CR42","doi-asserted-by":"publisher","first-page":"147337","DOI":"10.1016\/j.brainres.2021.147337","volume":"1758","author":"LF Rubio-Atonal","year":"2021","unstructured":"Rubio-Atonal LF, Serrano-Garc\u00eda N, Lim\u00f3n-Pacheco JH, Pedraza-Chaverri J, Orozco-Ibarra M. Cobalt protoporphyrin decreases food intake, body weight, and the number of neurons in the nucleus accumbens in female rats. Brain Res. 2021;1758:147337.","journal-title":"Brain Res"},{"key":"751_CR43","doi-asserted-by":"crossref","unstructured":"Galbraith RA, Kappas A. Cobalt protoporphyrin regulates body weight in beagle dogs: induction of weight loss in normal animals of stable adult weight. Pharmacology. 2008;43:96\u2013105.","DOI":"10.1159\/000138834"},{"key":"751_CR44","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/laban0208-81","volume":"37","author":"DC Fitzhugh","year":"2008","unstructured":"Fitzhugh DC, Parmer A, Shelton LJ, Sheets JT. A comparative analysis of carbon dioxide displacement rates for euthanasia of the ferret. Lab Anim. 2008;37:81\u20136.","journal-title":"Lab Anim"},{"key":"751_CR45","doi-asserted-by":"publisher","first-page":"S248","DOI":"10.4103\/2230-8210.104052","volume":"16","author":"N Kotwal","year":"2012","unstructured":"Kotwal N, Pandit A. Variability of capillary blood glucose monitoring measured on home glucose monitoring devices. Indian J Endocrinol Metab. 2012;16:S248\u201351.","journal-title":"Indian J Endocrinol Metab"},{"key":"751_CR46","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1538\/expanim.45.23","volume":"45","author":"Y Kato","year":"1996","unstructured":"Kato Y, Yamamoto M, Ikegami J, Okumura S, Hara T, Shuto K. A possible mechanism of increase in serum alkaline phosphatase activity in rats given granulocyte Colony-Stimulating factor. Exp Anim. 1996;45:23\u201332.","journal-title":"Exp Anim"},{"key":"751_CR47","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1159\/000009934","volume":"45","author":"H Fukumasu","year":"1998","unstructured":"Fukumasu H, Fukumasu Y, Ogita S. Elevation in plasma alkaline phosphatase level during rhG-CSF administration: granulocytopenic patients with gynecologic cancers treated with Cancer chemotherapy. Gynecol Obstet Invest. 1998;45:99\u2013104.","journal-title":"Gynecol Obstet Invest"},{"key":"751_CR48","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1053\/j.ackd.2008.04.003","volume":"15","author":"CL Edelstein","year":"2008","unstructured":"Edelstein CL. Biomarkers of acute kidney injury. Adv. Chronic Kidney Dis. 2008;15:222\u201334.","journal-title":"Adv Chronic Kidney Dis"},{"key":"751_CR49","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/B978-0-12-380920-9.00003-1","volume-title":"The laboratory rabbit, guinea pig, hamster, and other rodents","author":"IM Washington","year":"2012","unstructured":"Washington IM, Van Hoosier G. Clinical biochemistry and hematology. In: Suckow MA, Stevens KA, Wilson RP, editors. The laboratory rabbit, guinea pig, hamster, and other rodents. Boston: Academic; 2012. pp. 57\u2013116."},{"key":"751_CR50","volume-title":"Clinical methods: the history, physical, and laboratory examinations","author":"AO Hosten","year":"1990","unstructured":"Hosten AO. BUN and creatinine. In: Walker HK, Hall WD, Hurst JW, editors. Clinical methods: the history, physical, and laboratory examinations. Boston: Butterworths; 1990."},{"key":"751_CR51","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1046\/j.1537-2995.2001.41020184.x","volume":"41","author":"U Platzbecker","year":"2001","unstructured":"Platzbecker U, Prange-Krex G, Bornh\u00e4user M, Koch R, Soucek S, Aikele P, et al. Spleen enlargement in healthy donors during G\u2013CSF mobilization of PBPCs. Transfus (Paris). 2001;41:184\u20139.","journal-title":"Transfus (Paris)"},{"key":"751_CR52","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1046\/j.1537-2995.2003.00384.x","volume":"43","author":"D Stroncek","year":"2003","unstructured":"Stroncek D, Shawker T, Follmann D, Leitman SF. G-CSF-induced spleen size changes in peripheral blood progenitor cell donors. Transfus (Paris). 2003;43:609\u201313.","journal-title":"Transfus (Paris)"},{"key":"751_CR53","doi-asserted-by":"publisher","first-page":"bcr2017222561","DOI":"10.1136\/bcr-2017-222561","volume":"2018","author":"S Benguerfi","year":"2018","unstructured":"Benguerfi S, Thepault F, Lena H, Ricordel C. Spontaneous Splenic rupture as a rare complication of G-CSF injection. BMJ Case Rep. 2018;2018:bcr2017222561.","journal-title":"BMJ Case Rep"},{"key":"751_CR54","doi-asserted-by":"crossref","unstructured":"Jing W, Guo X, Qin F, Li Y, Wang G, Bi Y et al. G-CSF shifts erythropoiesis from bone marrow into spleen in the setting of systemic inflammation. Life Sci Alliance. 2021;4.","DOI":"10.26508\/lsa.202000737"},{"key":"751_CR55","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1159\/000350282","volume":"5","author":"N Strydom","year":"2013","unstructured":"Strydom N, Rankin SM. Regulation of Circulating neutrophil numbers under homeostasis and in disease. J Innate Immun. 2013;5:304\u201314.","journal-title":"J Innate Immun"},{"key":"751_CR56","doi-asserted-by":"publisher","first-page":"2762","DOI":"10.1038\/s41467-020-16596-9","volume":"11","author":"G Boivin","year":"2020","unstructured":"Boivin G, Faget J, Ancey PB, Gkasti A, Mussard J, Engblom C, et al. Durable and controlled depletion of neutrophils in mice. Nat Commun. 2020;11:2762.","journal-title":"Nat Commun"},{"key":"751_CR57","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.cyto.2008.03.002","volume":"42","author":"AD Panopoulos","year":"2008","unstructured":"Panopoulos AD, Watowich SS. Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and \u2018emergency\u2019 hematopoiesis. Cytokine. 2008;42:277\u201388.","journal-title":"Cytokine"},{"key":"751_CR58","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.annonc.2020.04.005","volume":"31","author":"M Clemons","year":"2020","unstructured":"Clemons M, Fergusson D, Simos D, Mates M, Robinson A, Califaretti N, et al. A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer. Ann Oncol. 2020;31:951\u20137.","journal-title":"Ann Oncol"},{"key":"751_CR59","first-page":"440","volume":"10","author":"P Coluccia","year":"2012","unstructured":"Coluccia P, Crovetti G, Del Fante C, Dallavalle FM, Laszl\u00f2 D, Ferremi P, et al. Screening of related donors and peripheral blood stem cell collection practices at different Italian apheresis centres. Blood Transfus. 2012;10:440\u20137.","journal-title":"Blood Transfus"},{"key":"751_CR60","first-page":"2651","volume":"20","author":"Y Shan","year":"2006","unstructured":"Shan Y, Lambrecht RW, Donohue SE, Bonkovsky HL. Role of Bach1 and Nrf2 in up-regulation of the Heme oxygenase-1 gene by Cobalt protoporphyrin. FASEB J Off Publ Fed Am Soc Exp Biol. 2006;20:2651\u20133.","journal-title":"FASEB J Off Publ Fed Am Soc Exp Biol"}],"container-title":["Pharmacological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-025-00751-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43440-025-00751-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-025-00751-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T04:15:55Z","timestamp":1758082555000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43440-025-00751-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,9]]},"references-count":60,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["751"],"URL":"https:\/\/doi.org\/10.1007\/s43440-025-00751-4","relation":{},"ISSN":["1734-1140","2299-5684"],"issn-type":[{"value":"1734-1140","type":"print"},{"value":"2299-5684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,9]]},"assertion":[{"value":"2 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 June 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"AJ, AS, and KS are co-inventors of the patents US10010557 and US10328085: Cobalt Porphyrins for the Treatment of Blood-Related Disorders and EP 3139917: Cobalt Protoporphyrin IX for the Treatment of Blood-Related Disorders, granted to Jagiellonian University. The remaining authors declare no conflict of interest.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}