Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndrome
Abstract Background Patients with liver diseases often have some form of anemia. Hematological dyscrasias are known side effects of antipsychotic drug medication and the occurrence of agranulocytosis under clozapine is well described. However, the sex-dependent impact of clozapine and haloperidol on...
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| Format: | Article |
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BMC
2022-01-01
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| Series: | BMC Pharmacology and Toxicology |
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| Online Access: | https://doi.org/10.1186/s40360-021-00544-4 |
| _version_ | 1819008676556439552 |
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| author | Marie-Luise Bouvier Karin Fehsel Andrea Schmitt Eva Meisenzahl-Lechner Wolfgang Gaebel Martina von Wilmsdorff |
| author_facet | Marie-Luise Bouvier Karin Fehsel Andrea Schmitt Eva Meisenzahl-Lechner Wolfgang Gaebel Martina von Wilmsdorff |
| author_sort | Marie-Luise Bouvier |
| collection | DOAJ |
| description | Abstract Background Patients with liver diseases often have some form of anemia. Hematological dyscrasias are known side effects of antipsychotic drug medication and the occurrence of agranulocytosis under clozapine is well described. However, the sex-dependent impact of clozapine and haloperidol on erythrocytes and symptoms like anemia, and its association with hepatic iron metabolism has not yet been completely clarified. Therefore, in the present study, we investigated the effect of both antipsychotic drugs on blood parameters and iron metabolism in the liver of male and female Sprague Dawley rats. Methods After puberty, rats were treated orally with haloperidol or clozapine for 12 weeks. Blood count parameters, serum ferritin, and liver transferrin bound iron were determined by automated counter. Hemosiderin (Fe3+) was detected in liver sections by Perl’s Prussian blue staining. Liver hemoxygenase (HO-1), 5’aminolevulinate synthase (ALAS1), hepcidin, heme-regulated inhibitor (HRI), cytochrome P4501A1 (CYP1A1) and 1A2 (CYP1A2) were determined by Western blotting. Results We found anemia with decreased erythrocyte counts, associated with lower hemoglobin and hematocrit, in females with haloperidol treatment. Males with clozapine medication showed reduced hemoglobin and increased red cell distribution width (RDW) without changes in erythrocyte numbers. High levels of hepatic hemosiderin were found in the female clozapine and haloperidol medicated groups. Liver HRI was significantly elevated in male clozapine medicated rats. CYP1A2 was significantly reduced in clozapine medicated females. Conclusions The characteristics of anemia under haloperidol and clozapine medication depend on the administered antipsychotic drug and on sex. We suggest that anemia in rats under antipsychotic drug medication is a sign of an underlying liver injury induced by the drugs. Changing hepatic iron metabolism under clozapine and haloperidol may help to reduce these effects of liver diseases. |
| first_indexed | 2024-12-21T00:44:16Z |
| format | Article |
| id | doaj.art-d4754b467a2648e39b87ca741a052710 |
| institution | Directory Open Access Journal |
| issn | 2050-6511 |
| language | English |
| last_indexed | 2024-12-21T00:44:16Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pharmacology and Toxicology |
| spelling | doaj.art-d4754b467a2648e39b87ca741a0527102022-12-21T19:21:35ZengBMCBMC Pharmacology and Toxicology2050-65112022-01-0123111210.1186/s40360-021-00544-4Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndromeMarie-Luise Bouvier0Karin Fehsel1Andrea Schmitt2Eva Meisenzahl-Lechner3Wolfgang Gaebel4Martina von Wilmsdorff5Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-UniversityDepartment of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-UniversityDepartment of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilians University MunichDepartment of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-UniversityDepartment of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-UniversityDepartment of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-UniversityAbstract Background Patients with liver diseases often have some form of anemia. Hematological dyscrasias are known side effects of antipsychotic drug medication and the occurrence of agranulocytosis under clozapine is well described. However, the sex-dependent impact of clozapine and haloperidol on erythrocytes and symptoms like anemia, and its association with hepatic iron metabolism has not yet been completely clarified. Therefore, in the present study, we investigated the effect of both antipsychotic drugs on blood parameters and iron metabolism in the liver of male and female Sprague Dawley rats. Methods After puberty, rats were treated orally with haloperidol or clozapine for 12 weeks. Blood count parameters, serum ferritin, and liver transferrin bound iron were determined by automated counter. Hemosiderin (Fe3+) was detected in liver sections by Perl’s Prussian blue staining. Liver hemoxygenase (HO-1), 5’aminolevulinate synthase (ALAS1), hepcidin, heme-regulated inhibitor (HRI), cytochrome P4501A1 (CYP1A1) and 1A2 (CYP1A2) were determined by Western blotting. Results We found anemia with decreased erythrocyte counts, associated with lower hemoglobin and hematocrit, in females with haloperidol treatment. Males with clozapine medication showed reduced hemoglobin and increased red cell distribution width (RDW) without changes in erythrocyte numbers. High levels of hepatic hemosiderin were found in the female clozapine and haloperidol medicated groups. Liver HRI was significantly elevated in male clozapine medicated rats. CYP1A2 was significantly reduced in clozapine medicated females. Conclusions The characteristics of anemia under haloperidol and clozapine medication depend on the administered antipsychotic drug and on sex. We suggest that anemia in rats under antipsychotic drug medication is a sign of an underlying liver injury induced by the drugs. Changing hepatic iron metabolism under clozapine and haloperidol may help to reduce these effects of liver diseases.https://doi.org/10.1186/s40360-021-00544-4ClozapineHaloperidolBlood dyscrasiaHepatic iron metabolism |
| spellingShingle | Marie-Luise Bouvier Karin Fehsel Andrea Schmitt Eva Meisenzahl-Lechner Wolfgang Gaebel Martina von Wilmsdorff Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndrome BMC Pharmacology and Toxicology Clozapine Haloperidol Blood dyscrasia Hepatic iron metabolism |
| title | Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndrome |
| title_full | Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndrome |
| title_fullStr | Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndrome |
| title_full_unstemmed | Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndrome |
| title_short | Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndrome |
| title_sort | sex dependent effects of long term clozapine or haloperidol medication on red blood cells and liver iron metabolism in sprague dawley rats as a model of metabolic syndrome |
| topic | Clozapine Haloperidol Blood dyscrasia Hepatic iron metabolism |
| url | https://doi.org/10.1186/s40360-021-00544-4 |
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