Lycopene attenuates dexamethasone induced depression like behavior and immunological dysfunction via restoration of neuro-immune-metabolic homeostasis in rats.

Authors

Hend A Essa

Published in

Scientific reports. Volume 16. Issue 1. Jul 19, 2026. Epub Jul 19, 2026.

Abstract

Chronic glucocorticoid therapy, while clinically indispensable, often induces debilitating neuropsychiatric side effects, including depression-like behaviors, alongside systemic immunosuppression and metabolic dysfunction. The convergence of central neurotoxicity and peripheral immune dysregulation presents a unique therapeutic challenge requiring multi-target interventions. This study investigated the prophylactic efficacy of lycopene against dexamethasone-induced behavioral, neurochemical, oxidative, inflammatory, and immunological perturbations in rats. Thirty-two adult male Sprague-Dawley rats were randomly assigned to four groups (n = 8): normal control, dexamethasone (2 mg/kg/day/intraperitoneal), lycopene (10 mg/kg/day/orally), and dexamethasone+lycopene combination. Treatments were administered daily for 21 days. Behavioral assessments (forced swim test, tail suspension test) were conducted. In frontal cortex and hippocampal tissues, neurochemical markers (brain-derived neurotrophic factor, gamma-aminobutyric acid, and acetylcholinesterase activity), neurotransmitters (serotonin, dopamine), oxidative stress markers (malondialdehyde, nitric oxide, reduced glutathione, superoxide dismutase, catalase), inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), and caspase-3 were quantified. In serum, fasting blood glucose, insulin, liver and kidney function markers, oxidative stress markers, inflammatory cytokines (interleukin-4, tumor necrosis factor-alpha, interferon-gamma), cluster of differentiation 4 and 8 concentrations (CD4, CD8), and complete blood count were analyzed. Dexamethasone significantly (p < 0.05) increased immobility time in behavioral tests, depleted serotonin and dopamine, elevated oxidative stress markers, and induced leukopenia with disrupted CD4/CD8 ratios. Lycopene co-treatment reversed behavioral despair, restored neurotransmitter homeostasis, attenuated oxidative-inflammatory cascades, normalized immune cell populations, and improved metabolic parameters. Lycopene provides integrated multi-system protection against glucocorticoid-induced neurobehavioral and immunological dysfunction, positioning it as a potential promising nutritional adjunct for patients requiring chronic corticosteroid therapy.

PMID:
42472869
Bibliographic data and abstract were imported from PubMed on 20 Jul 2026.

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