Liver Disease in Iron Overload

Guindi, Maha

doi:10.1016/b978-0-323-42873-6.00011-1

Cited by 4 publications

(3 citation statements)

References 123 publications

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“…Atypical antipsychotics like clozapine can induce the metabolic syndrome and NAFLD [ 40 ]. In female Sprague Dawley rats, clozapine and haloperidol lead to non-significantly higher serum ferritin and lower hepatic transferrin bound iron associated with a tenfold higher hepatic ferric ion (Fe 3+ ) retention as hemosiderin granules [ 41 ], the insoluble form of iron (Table 1 , Fig. 1 ), pointing to iron overload.…”

Section: Discussionmentioning

confidence: 99%

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

Bouvier

Fehsel

Schmitt

et al. 2022

BMC Pharmacol Toxicol

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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.

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Section: Discussionmentioning

confidence: 99%

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

Bouvier

Fehsel

Schmitt

et al. 2022

BMC Pharmacol Toxicol

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“…Prussian blue staining (Perl’s stain) is known to reveal ferric iron deposits in the neuropil of the brain (Churukian, 2008; Guindi, 2018; Xiao et al, 2023). This staining is of interest in neurodegenerative diseases, small vessel diseases, or white matter pathology detected by MRI, in which brains may be affected by such iron deposits (Connor & Benkovic, 1992; Dusek et al, 2022; Kruer, 2013; Roseborough et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

Comparison of histological procedures and antigenicity of human post-mortem brains fixed with solutions used in gross anatomy laboratories

Frigon,

Gérin-Lajoie,

Dadar

et al. 2024

Preprint

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Background: Brain banks provide small tissue samples to researchers, while gross anatomy laboratories could provide larger samples, including complete brains to neuroscientists. However, they are preserved with solutions appropriate for gross-dissection, different from the classic neutral-buffered formalin (NBF) used in brain banks. Our previous work in mice showed that two gross-anatomy laboratory solutions, a saturated-salt-solution (SSS) and an alcohol-formaldehyde-solution (AFS), preserve antigenicity of the main cellular markers. Our goal is now to compare the quality of histology and antigenicity preservation of human brains fixed with NBF by immersion (practice of brain banks) vs. those fixed with a SSS and an AFS by whole body perfusion, practice of gross-anatomy laboratories. Methods: We used a convenience sample of 42 brains (31 males, 11 females; 25-90 years old) fixed with NBF (N=12), SSS (N=13), and AFS (N=17). One cm3 tissue blocks were cut, cryoprotected, frozen and sliced into 40 um sections. The four cell populations were labeled using immunohistochemistry (neuronal-nuclei (NeuN), glial-fibrillary-acidic-protein (GFAP), ionized-calcium-binding-adaptor-molecule1 (Iba1) and myelin-proteolipid-protein (PLP)). We qualitatively assessed antigenicity and cell distribution, and compared the ease of manipulation of the sections, the microscopic tissue quality, and the quality of common histochemical stains (e.g., Cresyl violet, Luxol fast blue, etc.) across solutions. Results: Sections of SSS-fixed brains were more difficult to manipulate and showed poorer tissue quality than those from brains fixed with the other solutions. The four antigens were preserved, and cell labeling was more often homogenous in AFS-fixed specimens. NeuN and GFAP were not always present in the NBF and SSS samples. Some antigens were heterogeneously distributed in some specimens, independently of the fixative, but an antigen retrieval protocol successfully recovered them. Finally, the histochemical stains were of sufficient quality regardless of the fixative, although neurons were more often paler in SSS-fixed specimens. Conclusion: Antigenicity was preserved in human brains fixed with solutions used in human gross-anatomy (albeit the poorer quality of SSS-fixed specimens). For some specific variables, histology quality was superior in AFS-fixed brains. Furthermore, we show the feasibility of frequently used histochemical stains. These results are promising for neuroscientists interested in using brain specimens from anatomy laboratories.

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“…Prussian blue staining (Perl’s stain) is known to reveal ferric iron deposits in the neuropil of the brain ( Churukian, 2008 ; Guindi, 2018 ; Xiao et al, 2023 ). This staining is of interest in neurodegenerative diseases, small vessel diseases, or white matter pathology detected by MRI, in which brains may be affected by such iron deposits ( Connor and Benkovic, 1992 ; Kruer, 2013 ; Roseborough et al, 2020 ; Dusek et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Comparison of histological procedures and antigenicity of human post-mortem brains fixed with solutions used in gross anatomy laboratories

Frigon,

Gérin-Lajoie,

Dadar

et al. 2024

Front. Neuroanat.

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BackgroundBrain banks provide small tissue samples to researchers, while gross anatomy laboratories could provide larger samples, including complete brains to neuroscientists. However, they are preserved with solutions appropriate for gross-dissection, different from the classic neutral-buffered formalin (NBF) used in brain banks. Our previous work in mice showed that two gross-anatomy laboratory solutions, a saturated-salt-solution (SSS) and an alcohol-formaldehyde-solution (AFS), preserve antigenicity of the main cellular markers (neurons, astrocytes, microglia, and myelin). Our goal is now to compare the quality of histology and antigenicity preservation of human brains fixed with NBF by immersion (practice of brain banks) vs. those fixed with a SSS and an AFS by whole body perfusion, practice of gross-anatomy laboratories.MethodsWe used a convenience sample of 42 brains (31 males, 11 females; 25–90 years old) fixed with NBF (N = 12), SSS (N = 13), and AFS (N = 17). One cm3 tissue blocks were cut, cryoprotected, frozen and sliced into 40 μm sections. The four cell populations were labeled using immunohistochemistry (Neurons = neuronal-nuclei = NeuN, astrocytes = glial-fibrillary-acidic-protein = GFAP, microglia = ionized-calcium-binding-adaptor-molecule1 = Iba1 and oligodendrocytes = myelin-proteolipid-protein = PLP). We qualitatively assessed antigenicity and cell distribution, and compared the ease of manipulation of the sections, the microscopic tissue quality, and the quality of common histochemical stains (e.g., Cresyl violet, Luxol fast blue, etc.) across solutions.ResultsSections of SSS-fixed brains were more difficult to manipulate and showed poorer tissue quality than those from brains fixed with the other solutions. The four antigens were preserved, and cell labeling was more often homogeneous in AFS-fixed specimens. NeuN and GFAP were not always present in NBF and SSS samples. Some antigens were heterogeneously distributed in some specimens, independently of the fixative, but an antigen retrieval protocol successfully recovered them. Finally, the histochemical stains were of sufficient quality regardless of the fixative, although neurons were more often paler in SSS-fixed specimens.ConclusionAntigenicity was preserved in human brains fixed with solutions used in human gross-anatomy (albeit the poorer quality of SSS-fixed specimens). For some specific variables, histology quality was superior in AFS-fixed brains. Furthermore, we show the feasibility of frequently used histochemical stains. These results are promising for neuroscientists interested in using brain specimens from anatomy laboratories.

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Liver Disease in Iron Overload

Cited by 4 publications

References 123 publications

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

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

Comparison of histological procedures and antigenicity of human post-mortem brains fixed with solutions used in gross anatomy laboratories

Comparison of histological procedures and antigenicity of human post-mortem brains fixed with solutions used in gross anatomy laboratories

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