Impaired erythropoietin production in mice treated with cyclosporin A
| Autor: | Pierluigi Rossi Ferrini, Alberto Grossi, Alessandro M. Vannucchi, Rafanelli D, Renato Alterini, Alberto Bosi, Riccardo Saccardi, Stefano Guidi |
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| Rok vydání: | 1991 |
| Předmět: |
Male
medicine.medical_specialty Anemia Immunology Cyclosporins Hematocrit Biochemistry Nephrotoxicity chemistry.chemical_compound Mice Cyclosporin a Internal medicine hemic and lymphatic diseases medicine Animals Erythropoietin Bone Marrow Transplantation Creatinine medicine.diagnostic_test business.industry Cell Biology Hematology medicine.disease Transplantation Endocrinology chemistry Toxicity business medicine.drug |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v78.6.1615.bloodjournal7861615 |
| Popis: | Because recent data indicate that erythropoietin (Epo) production is defective in allogeneic bone marrow transplant (BMT) patients, we investigated the role of the immunosuppressant, nephrotoxic, agent cyclosporin A (CsA) on renal Epo production using an animal model. Mice were injected with 1.0 to 40.0 mg/kg/d CsA for 15 days. Thereafter, circulating Epo levels were evaluated in both intact animals and in mice made anemic with phenylhydrazine (PHZ). Serum Epo levels measured in CsA-treated animals were then compared with the predicted levels, which had been calculated in a reference population of normal, either intact or anemic, mice. In CsA-treated, intact animals both hematocrit and serum Epo levels were not significantly different from controls. However, serum Epo levels in CsA-treated, anemic mice were significantly lower than those expected in a control population of untreated, anemic mice with similar degrees of anemia. No significant increase in serum creatinine was recorded even at the highest doses of CsA used, nor were we able to document signs of renal toxicity by histologic examination of the kidneys. Therefore, therapeutical doses of CsA appear to affect the production of Epo under conditions in which the demand of the hormone is increased, as in response to anemia. We suggest that a subclinical kidney toxicity produced by CsA might have a role in the pathogenesis of the impaired Epo production observed in BMT patients, and may contribute to a delayed erythroid engraftment in at least some BMT patients. |
| Databáze: | OpenAIRE |
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