Folic Acid Mitigates Sertraline-Induced Liver Damage in Adult Female Albino Rats During Pregnancy and Postpartum: A Biochemical and Histological Study

Background and Objectives: Sertraline is a selective serotonin reuptake inhibitor (SSRI) that is frequently prescribed during pregnancy to treat mood disorders. Studies indicate that chronic use of sertraline is associated with elevated liver enzymes, oxidative stress, and histological alterations in the liver. Folic acid, a recommended supplement currently used during the first trimester of pregnancy, has antioxidant and anti-inflammatory effects. Hence, folic acid might be a potential protective agent against sertraline-induced liver injury. The current study aimed to investigate the possible hepatotoxic effects of sertraline administration during pregnancy and early postpartum. In addition, we sought to evaluate the potential protective effects of folic acid supplementation in alleviating any sertraline-induced liver damage. Materials and Methods: Eighty pregnant albino rats were randomly divided into four groups: control, folic acid-treated, sertraline-treated, and folic acid–sertraline-treated. Each group was divided into rats euthanized immediately after giving birth (0 h) or 14 days postpartum. Biochemical, histological, and immunohistochemical evaluations of liver function and structure were conducted. Results: Administration of sertraline was associated with a significant increase in hepatic enzymes (ALT and AST) and disrupted lipid profile (elevated cholesterol, triglycerides, and LDL-c) compared to the control group. Increased apoptosis was evidenced by increased caspase 3 expression and histological alterations, including vacuolation and inflammatory infiltrates, in sertraline-treated rats. Folic acid supplementation effectively mitigated these effects by preserving liver architecture, normalizing biochemical markers (ALT, AST, and lipid profile changes), and reducing apoptotic activity (lower caspase 3 expression). Conclusions: Folic acid mitigated sertraline-induced hepatic damage in pregnant rats. This suggests the potential benefits of using folic acid during the whole duration of pregnancy in patients treated with sertraline.