Impact of fluoxetine on liver damage in rats

Inkielewicz-Stępniak, Iwona

doi:10.1016/s1734-1140(11)70510-2

Cited by 75Drug-Induced Hepatotoxicity and ProtectionPharmacogenetics and Drug MetabolismImmunotoxicology and immune responses

Impact of fluoxetine on liver damage in rats

Inkielewicz-Stępniak, Iwona·2011·Pharmacological Reports

DOI 10.1016/s1734-1140(11)70510-2

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Abstract

Fluoxetine (Flux) is a fluorine-containing drug that selectively inhibits serotonin reuptake. It is widely prescribed as a treatment for depression disorders. Hepatic side effects have been reported during Flux therapy. These reports led us to investigate the involvement of oxidative stress mechanisms in liver injury caused by Flux. It has been shown that exposure to fluoride (F(-)) induces excessive production of free radicals and affects the antioxidant defense system. Based on this knowledge, we examined the F(-) concentration in serum and urine during administration of Flux. In our study, the effects of one month of Flux treatment on lipid and protein peroxidation, the concentration of uric acid in the liver and the activity of transaminases and transferases in the serum were investigated in rats. Eighteen adult male Wistar rats were divided into three equal groups of six animals each: (I) controls who drank tap water and received 1 ml of tap water intragastrically; (II) animals that received 8 mg Flux/kg bw/day intragastrically; and (III) animals that received 24 mg Flux/kg bw/day intragastrically. Flux treatment increased of the levels of carbonyl groups, thiobarbituric acid reactive species (TBARS) and the uric acid content in the liver. The activities of alanine transaminase (ALT), aspartate transaminase (AST) and glutathione-S transferase (GST) increased in the serum of the treated groups. The Flux levels in the plasma of the treated rats increased significantly in a dose-dependent manner. We observed no changes in the concentration of fluoride in either the serum or the urine of treated rats compared to the control group. In conclusion, our study indicates that Flux induces liver damage and mediates free radical reactions. Our data also indicate that Flux does not release F(-) during metabolism and does not affect physiological levels of F(-) in the serum or urine.

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Chronic fluoxetine treatment increases levels of TBARS, carbonyl groups, and uric acid content in the liver of male rats.
“Chronic fluoxetine treatment increased the levels of TBARS, carbonyl groups, and the uric acid content in the liver.”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [22]
Chronic fluoxetine treatment increases activities of ALT, AST, and GST in the serum of male rats.
“The activities of alanine transaminase (ALT), aspartate transaminase (AST), and GST were increased in the serum.”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [22]
The overall effects of chronic fluoxetine are more pronounced at the higher dose (24 versus 8 mg/kg).
“The overall effects are more pronounced in the higher dose (24 versus 8 mg/kg) [22].”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [22]

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Authors: Inkielewicz-Stępniak, I.
Venue: Pharmacological Reports
Publisher: Springer Science and Business Media LLC
Published: 2011-03
Volume: 63
Issue: 2
Pages: 441-447
ISSN: 1734-1140 (ISSN-L)
DOI: 10.1016/s1734-1140(11)70510-2
OpenAlex: W2029455988
Semantic Scholar: c29411fe9967a3162f814badc7db626de234bc03
Cited by: 75
References: 48
Citations by year: 2026: 1 · 2025: 2 · 2024: 9 · 2023: 5 · 2022: 10 · 2021: 9 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 6 · 2016: 6 · 2015: 7 · 2014: 6 · 2013: 2 · 2012: 4
FWCI: 4.05
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacological Reports (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
Keywords: fluoxetine, drug-induced liver injury, fluoride, oxidative stress, lipid peroxidation, protein carbonylation, uric acid, transaminases, glutathione S-transferase, dose-dependent toxicity
MeSH terms: Animals, Dose-Response Relationship, Drug, Fluorides, Fluoxetine, Free Radicals, Male, Uric Acid, Lipid Peroxidation, Rats, Wistar, Selective Serotonin Reuptake Inhibitors, Oxidative Stress, Rats, Chemical and Drug Induced Liver Injury

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Impact of fluoxetine on liver damage in rats

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