Effects of fennel seed oil on Nrf2 pathway in paracetamol-induced hepatoxicity in rats

Abstract

Introduction: Liver diseases represent a major global health problem. The use of medicinal plants for treating liver diseases have been common since ancient times. However the mechanisms underlying the beneficial actions of some medicinal plants are not fully elucidated. We investigated the potential hepatoprotective mechanisms of fennel seed essential oil (FSO) focusing on Nrf2 pathway against paracetamol-induced hepatotoxicity in rats. Method: Adult male Wistar rats were randomly assigned to 4 groups, 6 rats each. Group 1 received saline i.p. for 7 days, group 2 received paracetamol (single dose, 2 g/kg, p.o.), group 3 received silymarin (100 mg/kg/day, p.o. for 7 days) followed 1 h later by paracetamol administration, group 4 received FSO (0.5 mg/kg/day, i.p. for 7 days) followed by paracetamol administration. Blood samples and liver tissues were harvested 24 h after paracetamol administration. Activity of serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and serum bilirubin level were measured as indicators of liver function. Liver lysate content of reduced (GSH) and oxidized glutathione (GSSG), malondialdehyde (MDA), nuclear erythroid 2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), glutamate cysteine ligase (GCL) were measured as well as glutathione reductase (GR) activity. Standardization of FSO was carried out using gas chromatoghraphy-mass spectrometry. Results: Both silymarin and FSO reduced serum ALT, ALP, AST, and bilirubin levels in parallel with decreased hepatic MDA level and increased GSH/GSSG ratio indicating significant improvements in liver function and redox status. FSO proved superior to silymarin in its antioxidant effects. This beneficial effect of FSO is likely secondary to the observed increases in liver content of Nrf2, HO-1 and GCL.Conclusion: Pretreatment with FSO exhibited a hepatoprotective effect against paracetamol-induced hepatotoxicity via upregulation of Nrf2 and its target proteins HO-1 and GCL.