Lycopene Mitigates Sertraline-Triggered Hepatotoxicity: Modulation of Oxidative Stress and Liver Enzymes

Sadeghzadeh, Ayla; Kargar Jahromi, Hossein; Bahman Jahromi, Enayatollah

doi:10.22092/ari.2026.370470.3805

Lycopene Mitigates Sertraline-Triggered Hepatotoxicity: Modulation of Oxidative Stress and Liver Enzymes

Articles in Press

Document Type : Original Articles

Authors

¹ Department of chemistry, Ja.C., Islamic Azad University, Jahrom, Iran

² Research Center for Noncommunicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran.

10.22092/ari.2026.370470.3805

Abstract

Liver dysfunction poses a serious threat to systemic homeostasis, and drug-induced oxidative stress (OS) is the main factor in its induction. Sertraline, a commonly prescribed selective serotonin reuptake inhibitor, can cause liver damage through increasing OS and impaired liver enzyme activity. Lycopene, a potent lipophilic antioxidant, may counteract these effects by scavenging free radicals and OS. This study aimed to investigate the hepatoprotective effects of lycopene in reducing sertraline-induced hepatotoxicity in a rat model, focusing on OS parameters and liver-specific enzymes.Forty-eight male Wistar rats were randomly divided into six groups to evaluate the protective effects of lycopene in reducing sertraline-induced liver injury. They were treated for 28 days via oral gavage with sertraline alone or in combination with different doses of lycopene (12.5, 25, and 50 mg/kg). Biochemical analyses were performed on serum samples to assess liver enzymes (AST, ALT, ALP), total bilirubin, malondialdehyde (MDA), and total antioxidant capacity (TAC). Statistical significance was determined using analysis of variance followed by Tukey's post hoc test.
Sertraline administration significantly increased serum concentrations of AST, ALT, ALP, MDA, and total bilirubin, while decreasing TAC (p<0.001 for all ANOVA comparisons). Co-administration treatment with lycopene, especially at a dose of 50 mg/kg, significantly reversed these changes by reducing liver enzymes and OS markers and restoring TAC (p<0.001). The hepatoprotective effect of lycopene was dose-dependent and was greatest at the highest concentration.
Lycopene demonstrated a dose-dependent protective effect against sertraline-induced hepatotoxicity by reducing OS and improving key biochemical markers. The 50 mg/kg dose provided the greatest benefit, indicating its potential as a therapeutic adjunct. These results highlight the antioxidant efficacy of lycopene and support further research into its mechanistic pathways, pharmacodynamics, and long-term safety in drug-induced liver injury models.

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