Cardiac and hepatic side effects of fluoxetine in male and female adolescent rats

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2023-11-08 DOI:10.1111/fcp.12963

Hajar Babaaeyan, Nona Sakhaie, Farshid Sadegzadeh, Hakimeh Saadati, Ali Niapour

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引用次数: 0

Abstract

Background

Fluoxetine (FLX) is widely prescribed as an antidepressant medicine in the juvenile population.

Objectives

Although some adverse effects of FLX have been reported in adults, the present study aimed to investigate the side effects of FLX treatment during adolescence on the cardiac and hepatic systems.

Methods

Male and female rats were gavaged with FLX (5 mg/kg/day) on postnatal days (PND) 21 to PND 60. Following treatment, blood samples were collected and hepatic enzymes were evaluated. The specimens of the liver and heart of animals were subjected to histopathological assessment.

Results

Fluoxetine significantly raised serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in males, whereas the aspartate aminotransferase (AST) level increased in both male and female animals. In the histopathological study, hepatic plates were more seriously affected, and the sinusoids were irregular in adolescent male rats. Degenerative changes were observed especially in the first and second hepatic zones of FLX-treated male rats. Signs of inflammation and accumulation of lymphoid groups were frequently observed in the portal triad of the hepatic lobules. These alterations were more severe in male livers. Minimum or nearly normal changes were observed in female liver slides. In addition, the histological assessment indicated that treatment with FLX during adolescence also increased the heart's weight and the wall thickness of the right and left ventricles (hypertrophy) in male and especially female animals.

Conclusion

Our findings may provide new insights into the cardiac and hepatic adverse effects of FLX.

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氟西汀对雄性和雌性青春期大鼠的心脏和肝脏副作用。

背景：氟西汀（FLX）在青少年人群中被广泛用作抗抑郁药物。目的：尽管FLX在成人中有一些不良反应的报道，但本研究旨在调查青少年时期FLX治疗对心脏和肝脏系统的副作用。方法：雄性和雌性大鼠于出生后21至60天灌胃FLX（5mg/kg/天）。治疗后，采集血样并评估肝酶。对动物的肝脏和心脏标本进行组织病理学评估。结果：氟西汀显著提高雄性动物的血清丙氨酸氨基转移酶（ALT）和碱性磷酸酶（ALP），而雄性和雌性动物的天冬氨酸氨基转移酶水平均升高。在组织病理学研究中，青春期雄性大鼠的肝板受影响更严重，血窦不规则。观察到变性变化，尤其是在FLX处理的雄性大鼠的第一和第二肝区。在肝小叶的门脉三联体中经常观察到炎症和淋巴群聚集的迹象。这些变化在男性肝脏中更为严重。在女性肝载玻片中观察到最小或几乎正常的变化。此外，组织学评估表明，在青春期接受FLX治疗也会增加雄性动物，尤其是雌性动物的心脏重量和左右心室壁厚（肥大）。结论：我们的研究结果可能为FLX的心脏和肝脏不良反应提供新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.