Protective role of ellagic acid and taurine against fluoxetine induced hepatotoxic effects on biochemical and oxidative stress parameters, histopathological changes, and gene expressions of IL-1β, NF-κB, and TNF-α in male Wistar rats

Abstract

Purposes: Hepatic bioactivation of fluoxetine (FXN) could increase free radicals' generation provoking hepatotoxicity. Therefore, the protective effects of ellagic acid (EA) and taurine (TAU) treatments against fluoxetine-induced liver damage in rats were examined.

Materials and methods: Sixty four male Wistar rats were randomly assigned to 8 groups (n = 8). Group (1) Control, group (2) FXN, group (3) FXN + EA, group (4) FXN + TAU, group (5) FXN + EA + TAU, group (6) EA, group (7) TAU, and group (8) EA + TAU. Then, the serum and tissue parameters of the oxidative stress were examined.

Key findings: FXN significantly raised serum MDA, protein carbonyl, lipid profile, ALT, AST, ALP, total bilirubin, serum IL-1β; and gene expressions of IL-1β, NF-κB, and TNF-α. Moreover, it significantly decreased HDL-C, ferric reducing antioxidant power (FRAP), catalase activity, vitamin C, and SOD activity in the liver compared to group 1. When compared to group 2, EA and TAU treatment dramatically increased antioxidant capacity and lowered hepatotoxic biochemical markers and cellular inflammation. Results also showed a protective effect of treatment against oxidative damage caused by hepatocytes' cytoarchitecture.

Significance: Our study concluded the beneficial effects of EA and TAU on FXN-induced hepatotoxicity. These effects were derived from free radical scavenging properties and the anti-inflammatory effects related to IL-1β, NF-κB, and TNF-α gene expression inhibition.

Keywords: Ellagic acid; Fluoxetine; Hepatoprotective; Inflammation; Oxidative stress; Taurine.