Different Therapeutic Doses of Sertraline Induce Liver Damage in Male Rats.

Abstract

Introduction: Sertraline is a first-line pharmacological treatment for Major Depressive Disorder (MDD) but can cause adverse effects, including acute hepatitis. This study aims to investigate, using an experimental male rat model, the effects of different therapeutic doses of sertraline on liver damage.

Material and methods: Forty adult male Wistar rats were randomly divided into 5 groups (n=8): a control group and four groups receiving daily oral sertraline at doses of 20, 50, 100, and 200 mg/kg for two months. After the treatment period, serum levels of liver enzymes (AST, ALT, ALP), bilirubin, lipid profile (cholesterol, LDL, HDL), and inflammatory cytokines (TNF-α, IL- 6) were measured. Data were analyzed using SPSS 20 software with one-way ANOVA and ttest.

Results: The control group showed the lowest mean levels of all measured parameters. A clear dose-dependent increase was observed for cholesterol, LDL, bilirubin, AST, ALT, ALP, TNF-α, and IL-6, with the 200 mg/kg group consistently exhibiting the highest values. All variables in the 200 mg/kg group were significantly elevated compared to the control group (p<0.05). Among liver enzymes, ALP demonstrated the most pronounced dose-response, whereas bilirubin showed the weakest association with sertraline dosage.

Discussion: The findings demonstrate clear dose-dependent hepatotoxicity for sertraline, involving hepatic enzyme leakage, dyslipidemia, and pro-inflammatory cytokine activation. This provides experimental validation for clinical case reports of sertraline-induced liver injury.

Conclusion: Sertraline causes dose-dependent liver damage in male rats, characterized by elevated liver enzymes, increased inflammatory markers, and adverse lipid changes. These results highlight the need for vigilant liver function monitoring in patients on higher therapeutic doses.