{"title":"Effect of taxifolin on clozapine-induced experimental oxidative and inflammatory heart damage in rats","authors":"Emine Fusun Akyuz Cim , Halis Suleyman","doi":"10.1016/j.amp.2023.08.004","DOIUrl":null,"url":null,"abstract":"<div><h3>Aim</h3><div><span>Clozapine is an atypical antipsychotic (AAP) drug used in treatment-resistant schizophrenia patients. The adverse effects of clozapine<span> on the heart may result in death and require drug discontinuation. Inflammatory mechanisms are thought to be responsible for the negative effect of clozapine on the heart. This suggests that using an agent with anti-inflammatory and antioxidant properties, which may be specific to clozapine-induced heart damage, may prevent possible damage. The aim of our study is to evaluate the effect of taxifolin (</span></span><em>3</em>,<em>5</em>,<em>7</em>,<em>3</em>’,<em>4’-pentahydroxy</em> flavanone), an agent with known antioxidant and anti-inflammatory effects, on myocardial damage caused by clozapine with biochemical and histopathological data.</div></div><div><h3>Material and method</h3><div>The rats were divided into three equal groups: healthy control group (HC), clozapine-treated group (CLN), and taxifolin<!--> <!-->+<!--> <!-->clozapine-treated group (TCL). To perform this experiment, taxifolin was administered to TCL (n-6) rats at a dose of 50<!--> <!-->mg/kg orally by gavage into the stomach. In the HC (n-6) and CLN (n-6) groups, the same volume of distilled water was administered orally as a solvent. One hour after the administration of taxifolin and distilled water, clozapine was administered orally at a dose of 20<!--> <!-->mg/kg to the TCL and CLN groups once a day for 28 days. At the end of the period, troponin I (TP I) and creatine kinase MB (CK-MB) levels were measured in the venous blood of each group. Malondialdehyde (MDA), total glutathione (tGSH), TNF-α, NF-<figure><img></figure>B, and IL-1β levels were measured in samples taken from heart tissues. Additionally, heart tissues were evaluated histopathologically.</div></div><div><h3>Results</h3><div>Troponin I, CK-MB, MDA, TNF-α, NF-<figure><img></figure>B, and IL-1β levels, myocardial degeneration, myofiber irregularity, and congestion scores were significantly higher and tGSH levels were lower in the clozapine group than in the healthy control and taxifolin<!--> <!-->+<!--> <!-->clozapine groups (<em>P</em> <!--><<!--> <!-->0.05). Compared with the healthy control group, troponin I, tGSH, and NF-KB levels were similar (<em>P</em> <!-->><!--> <!-->0.05), CK-MB, MDA, TNF-α, and IL-1β levels were higher in the taxifolin<!--> <!-->+<!--> <!-->clozapine group, while they were significantly lower than the clozapine group (<em>P</em> <!--><<!--> <!-->0.05). Histopathologically evaluated myocardial degeneration, myofiber irregularity, and congestion score were significantly lower in the taxifolin<!--> <!-->+<!--> <!-->clozapine group than in the clozapine group. In the clozapine group (CLN group), myofibers were found to have irregular patterns and were observed as irregular. In the taxifolin<!--> <!-->+<!--> <!-->clozapine group (TLC group), myofibrils generally showed a regular morphology.</div></div><div><h3>Conclusion</h3><div>We found that taxifolin can ameliorate damage to myocardial tissue by regulating oxidant-antioxidant and proinflammatory cytokine levels. The data of our study suggest that taxifolin may be useful in the treatment of clozapine-induced myocardial injury.</div></div>","PeriodicalId":7992,"journal":{"name":"Annales medico-psychologiques","volume":"182 9","pages":"Pages 823-829"},"PeriodicalIF":0.5000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annales medico-psychologiques","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0003448723002317","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PSYCHIATRY","Score":null,"Total":0}
引用次数: 0
Abstract
Aim
Clozapine is an atypical antipsychotic (AAP) drug used in treatment-resistant schizophrenia patients. The adverse effects of clozapine on the heart may result in death and require drug discontinuation. Inflammatory mechanisms are thought to be responsible for the negative effect of clozapine on the heart. This suggests that using an agent with anti-inflammatory and antioxidant properties, which may be specific to clozapine-induced heart damage, may prevent possible damage. The aim of our study is to evaluate the effect of taxifolin (3,5,7,3’,4’-pentahydroxy flavanone), an agent with known antioxidant and anti-inflammatory effects, on myocardial damage caused by clozapine with biochemical and histopathological data.
Material and method
The rats were divided into three equal groups: healthy control group (HC), clozapine-treated group (CLN), and taxifolin + clozapine-treated group (TCL). To perform this experiment, taxifolin was administered to TCL (n-6) rats at a dose of 50 mg/kg orally by gavage into the stomach. In the HC (n-6) and CLN (n-6) groups, the same volume of distilled water was administered orally as a solvent. One hour after the administration of taxifolin and distilled water, clozapine was administered orally at a dose of 20 mg/kg to the TCL and CLN groups once a day for 28 days. At the end of the period, troponin I (TP I) and creatine kinase MB (CK-MB) levels were measured in the venous blood of each group. Malondialdehyde (MDA), total glutathione (tGSH), TNF-α, NF-B, and IL-1β levels were measured in samples taken from heart tissues. Additionally, heart tissues were evaluated histopathologically.
Results
Troponin I, CK-MB, MDA, TNF-α, NF-B, and IL-1β levels, myocardial degeneration, myofiber irregularity, and congestion scores were significantly higher and tGSH levels were lower in the clozapine group than in the healthy control and taxifolin + clozapine groups (P < 0.05). Compared with the healthy control group, troponin I, tGSH, and NF-KB levels were similar (P > 0.05), CK-MB, MDA, TNF-α, and IL-1β levels were higher in the taxifolin + clozapine group, while they were significantly lower than the clozapine group (P < 0.05). Histopathologically evaluated myocardial degeneration, myofiber irregularity, and congestion score were significantly lower in the taxifolin + clozapine group than in the clozapine group. In the clozapine group (CLN group), myofibers were found to have irregular patterns and were observed as irregular. In the taxifolin + clozapine group (TLC group), myofibrils generally showed a regular morphology.
Conclusion
We found that taxifolin can ameliorate damage to myocardial tissue by regulating oxidant-antioxidant and proinflammatory cytokine levels. The data of our study suggest that taxifolin may be useful in the treatment of clozapine-induced myocardial injury.
期刊介绍：
The Annales Médico-Psychologiques is a peer-reviewed medical journal covering the field of psychiatry. Articles are published in French or in English. The journal was established in 1843 and is published by Elsevier on behalf of the Société Médico-Psychologique.
The journal publishes 10 times a year original articles covering biological, genetic, psychological, forensic and cultural issues relevant to the diagnosis and treatment of mental illness, as well as peer reviewed articles that have been presented and discussed during meetings of the Société Médico-Psychologique.To report on the major currents of thought of contemporary psychiatry, and to publish clinical and biological research of international standard, these are the aims of the Annales Médico-Psychologiques.
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