The Possible Ameliorating Role of Fisetin on Hepatic Changes Induced by Fluoxetine in Adult Male Albino Rats: Histological, Immunohistochemical, and Biochemical Study

BACKGROUND: Fluoxetine (FLX) is one of the selective serotonin reuptake inhibitors, it is widely used to treat neuropsychiatric disorders including depression, but high doses can cause several adverse effects. Fisetin (FIS), a bioactive flavonoid presents in vegetables and fruits, has antioxidant, anti-inflammatory, and anticancer effects. AIM: To evaluate the possible ameliorating effect of FIS on the hepatic alterations induced by FLX in adult male albino rats. MATERIALS AND METHODS: Our study was done, for 3-weeks, on 48 rats that were divided into four groups: Group I (control), Group II received FIS orally (100 mg/kg/day), Group III received FLX orally (10 mg/kg/day), and Group IV concomitantly received FLX and FIS at the same dose and manner of groups II and III. Blood and liver samples were obtained and prepared for histological, immunohistochemical, and biochemical studies. RESULTS: FLX group revealed disturbed liver architecture, hepatocytes with vacuolated cytoplasm, inflammatory cellular infiltration, blood extravasation, and congestion of blood vessels in addition to, a significant increase in the area percentage of caspase-3, inducible nitric oxide synthase and the number of glial fibrillary acidic protein-expressing cells as well as a significant decrease in the area percentage of periodic acid–Schiff stain. Moreover, FLX significantly increased aspartate-aminotransferase and alanine-aminotransferase levels in the serum. In addition, FLX increased malondialdehyde level and decreased superoxide dismutase, glutathione (GSH) peroxidase, and reduced GSH levels in liver tissue. The concomitant administration of FIS ameliorated these alterations. CONCLUSIONS: Administration of FIS ameliorated the histological, immunohistochemical, and biochemical alterations induced by FLX in the liver of adult male albino rats.