Mechanisms of oral ciprofloxacin-induced depressive-like behavior and the potential benefit of lactulose: A correlation analysis

Prolonged administration of antibiotics may be associated with depression due to the potential risk of dysbiosis. Thus, the restoration of microbial balance, through administration of prebiotics, might overcome the problem. This study investigated the mechanisms of antibiotic-induced depression, whi...

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Main Authors: Havizur Rahman, Kusnandar Anggadiredja, Lucy Sasongko
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Toxicology Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2214750025000381
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author Havizur Rahman
Kusnandar Anggadiredja
Lucy Sasongko
author_facet Havizur Rahman
Kusnandar Anggadiredja
Lucy Sasongko
author_sort Havizur Rahman
collection DOAJ
description Prolonged administration of antibiotics may be associated with depression due to the potential risk of dysbiosis. Thus, the restoration of microbial balance, through administration of prebiotics, might overcome the problem. This study investigated the mechanisms of antibiotic-induced depression, which were explored through statistical correlation analysis. The potential benefit of lactulose, a prebiotic, on this behavioral disorder was further assessed. The rats were assigned to groups receiving 102.8 mg/kg ciprofloxacin daily for 1, 8, 15, or 22 days. A different group of rat was given the same regimen for 8 days accompanied with lactulose at 2056 mg/kg. Upon completion of ciprofloxacin administration, the rats were tested for depression-like behavior (forced swimming test, FST; and sucrose preference test, SPT). They were then sacrificed for biochemical assessment in the hippocampus and prefrontal cortex. The mechanism studies revealed significant correlation between SPT vs. serotonin in the hippocampus, and SPT vs. serotonin, cortisol, NF-κB in the prefrontal cortex. Meanwhile, FST was significantly correlated with serotonin in the hippocampus and the prefrontal cortex, while in the prefrontal cortex it was significantly correlated with cortisol, NF-κB, and IL-6. Based on the afore-mentioned results, it was found that lactulose improved FST by targeting serotonin in the hippocampus. This study indicate that ciprofloxacin induce depression-like behavior via modulation of several neurotransmitter system as well as proinflammatory cytokines in the hippocampus and prefrontal cortex. The results further suggest the potential of lactulose to improve this behavior.
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spelling doaj-art-975d57e2e727489ea46af702ef0906f22025-01-27T04:21:59ZengElsevierToxicology Reports2214-75002025-06-0114101920Mechanisms of oral ciprofloxacin-induced depressive-like behavior and the potential benefit of lactulose: A correlation analysisHavizur Rahman0Kusnandar Anggadiredja1Lucy Sasongko2Department of Pharmaceutics, School of Pharmacy, Institut Teknologi Bandung, Bandung 41116, Indonesia; Department of Pharmacy, Faculty of Medicine and Health Sciences, University of Jambi, Jambi 36361, IndonesiaDepartment of Pharmacology and Clinical Pharmacy, School of Pharmacy, Institut Teknologi Bandung, Bandung 41116, IndonesiaDepartment of Pharmaceutics, School of Pharmacy, Institut Teknologi Bandung, Bandung 41116, Indonesia; Corresponding author.Prolonged administration of antibiotics may be associated with depression due to the potential risk of dysbiosis. Thus, the restoration of microbial balance, through administration of prebiotics, might overcome the problem. This study investigated the mechanisms of antibiotic-induced depression, which were explored through statistical correlation analysis. The potential benefit of lactulose, a prebiotic, on this behavioral disorder was further assessed. The rats were assigned to groups receiving 102.8 mg/kg ciprofloxacin daily for 1, 8, 15, or 22 days. A different group of rat was given the same regimen for 8 days accompanied with lactulose at 2056 mg/kg. Upon completion of ciprofloxacin administration, the rats were tested for depression-like behavior (forced swimming test, FST; and sucrose preference test, SPT). They were then sacrificed for biochemical assessment in the hippocampus and prefrontal cortex. The mechanism studies revealed significant correlation between SPT vs. serotonin in the hippocampus, and SPT vs. serotonin, cortisol, NF-κB in the prefrontal cortex. Meanwhile, FST was significantly correlated with serotonin in the hippocampus and the prefrontal cortex, while in the prefrontal cortex it was significantly correlated with cortisol, NF-κB, and IL-6. Based on the afore-mentioned results, it was found that lactulose improved FST by targeting serotonin in the hippocampus. This study indicate that ciprofloxacin induce depression-like behavior via modulation of several neurotransmitter system as well as proinflammatory cytokines in the hippocampus and prefrontal cortex. The results further suggest the potential of lactulose to improve this behavior.http://www.sciencedirect.com/science/article/pii/S2214750025000381MechanismsAnalyticalMethodsOral ciprofloxacinBehaviorDepression
spellingShingle Havizur Rahman
Kusnandar Anggadiredja
Lucy Sasongko
Mechanisms of oral ciprofloxacin-induced depressive-like behavior and the potential benefit of lactulose: A correlation analysis
Toxicology Reports
Mechanisms
Analytical
Methods
Oral ciprofloxacin
Behavior
Depression
title Mechanisms of oral ciprofloxacin-induced depressive-like behavior and the potential benefit of lactulose: A correlation analysis
title_full Mechanisms of oral ciprofloxacin-induced depressive-like behavior and the potential benefit of lactulose: A correlation analysis
title_fullStr Mechanisms of oral ciprofloxacin-induced depressive-like behavior and the potential benefit of lactulose: A correlation analysis
title_full_unstemmed Mechanisms of oral ciprofloxacin-induced depressive-like behavior and the potential benefit of lactulose: A correlation analysis
title_short Mechanisms of oral ciprofloxacin-induced depressive-like behavior and the potential benefit of lactulose: A correlation analysis
title_sort mechanisms of oral ciprofloxacin induced depressive like behavior and the potential benefit of lactulose a correlation analysis
topic Mechanisms
Analytical
Methods
Oral ciprofloxacin
Behavior
Depression
url http://www.sciencedirect.com/science/article/pii/S2214750025000381
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