دورية أكاديمية
The harmful acute effects of clomipramine in the rat liver: Impairments in mitochondrial bioenergetics.
| العنوان: | The harmful acute effects of clomipramine in the rat liver: Impairments in mitochondrial bioenergetics. |
|---|---|
| المؤلفون: | Bizerra PFV; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Itou da Silva FS; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Gilglioni EH; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Nanami LF; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Klosowski EM; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil., de Souza BTL; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Raimundo AFG; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Dos Santos KBP; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Mewes JM; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Constantin RP; Department of Biochemistry, Laboratory of Plant Biochemistry, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Mito MS; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Ishii-Iwamoto EL; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Constantin J; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Mingatto FE; Laboratory of Metabolic and Toxicological Biochemistry, São Paulo State University, Dracena 17900-000, São Paulo, Brazil., Esquissato GNM; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Marchiosi R; Department of Biochemistry, Laboratory of Plant Biochemistry, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Dos Santos WD; Department of Biochemistry, Laboratory of Plant Biochemistry, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Ferrarese-Filho O; Department of Biochemistry, Laboratory of Plant Biochemistry, State University of Maringá, Maringá 87020-900, Paraná, Brazil., Constantin RP; Department of Biochemistry, Laboratory of Biological Oxidations, State University of Maringá, Maringá 87020-900, Paraná, Brazil; Department of Biochemistry, Laboratory of Plant Biochemistry, State University of Maringá, Maringá 87020-900, Paraná, Brazil. Electronic address: rpconstantin@uem.br. |
| المصدر: | Toxicology letters [Toxicol Lett] 2023 Jul 01; Vol. 383, pp. 1-16. Date of Electronic Publication: 2023 May 20. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7709027 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3169 (Electronic) Linking ISSN: 03784274 NLM ISO Abbreviation: Toxicol Lett Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: Amsterdam, Elsevier/North Holland. |
| مواضيع طبية MeSH: | Clomipramine*/toxicity , Clomipramine*/metabolism , Chemical and Drug Induced Liver Injury*/metabolism, Rats ; Animals ; Energy Metabolism ; Liver/metabolism ; Mitochondria/metabolism ; Adenosine Triphosphate/metabolism ; Mitochondria, Liver/metabolism |
| مستخلص: | Clomipramine, a tricyclic antidepressant used to treat depression and obsessive-compulsive disorder, has been linked to a few cases of acute hepatotoxicity. It is also recognized as a compound that hinders the functioning of mitochondria. Hence, the effects of clomipramine on mitochondria should endanger processes that are somewhat connected to energy metabolism in the liver. For this reason, the primary aim of this study was to examine how the effects of clomipramine on mitochondrial functions manifest in the intact liver. For this purpose, we used the isolated perfused rat liver, but also isolated hepatocytes and isolated mitochondria as experimental systems. According to the findings, clomipramine harmed metabolic processes and the cellular structure of the liver, especially the membrane structure. The considerable decrease in oxygen consumption in perfused livers strongly suggested that the mechanism of clomipramine toxicity involves the disruption of mitochondrial functions. Coherently, it could be observed that clomipramine inhibited both gluconeogenesis and ureagenesis, two processes that rely on ATP production within the mitochondria. Half-maximal inhibitory concentrations for gluconeogenesis and ureagenesis ranged from 36.87 μM to 59.64 μM. The levels of ATP as well as the ATP/ADP and ATP/AMP ratios were reduced, but distinctly, between the livers of fasted and fed rats. The results obtained from experiments conducted on isolated hepatocytes and isolated mitochondria unambiguously confirmed previous propositions about the effects of clomipramine on mitochondrial functions. These findings revealed at least three distinct mechanisms of action, including uncoupling of oxidative phosphorylation, inhibition of the F Competing Interests: Declaration of Competing Interest The authors affirm that they have no known financial or interpersonal conflicts that would have seemed to influence the research that is the subject of this publication. (Copyright © 2023 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Cellular structure; Intact liver; Isolated hepatocytes; Isolated mitochondria; Mitochondrial toxicity; Tricyclic antidepressants |
| المشرفين على المادة: | NUV44L116D (Clomipramine) 8L70Q75FXE (Adenosine Triphosphate) |
| تواريخ الأحداث: | Date Created: 20230522 Date Completed: 20230731 Latest Revision: 20230731 |
| رمز التحديث: | 20230731 |
| DOI: | 10.1016/j.toxlet.2023.05.008 |
| PMID: | 37217012 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-3169 |
|---|---|
| DOI: | 10.1016/j.toxlet.2023.05.008 |