Effect of Lycopene and Genistein on Hepatic Inflammation and Fibrosis in Thioacetamide Induced Liver Injury in Rats

Abstract

Lycopene, a red crystalline carotenoid, and genistein, a phytoestrogen, have shown considerable promise as effective agents for chronic diseases prevention by reducing oxidative stress. The objective of this experiment was to elucidate the protective effect of lycopene, genistein and their combination against thioacetamide-induced chronic liver injury. Thirty-five rats were randomized into five groups: one untreated group (Control) and four groups treated with the hepatotoxicant thioacetamide (TAA) 200 mg/kg b.w. i.p., for 8 weeks. Concomitantly, the rats received a standard diet (control and TAA), lycopene 6 mg/kg, p.o. (TAA+L), genistein 1 mg/kg, p.o. (TAA+G) or lycopene and genistein (TAA+L+G). After 8 weeks of treatment, the rats were killed and blood and liver samples were collected. TAA administration elevated liver malondialdehyde (MDA), collagen type 1, tumor necrosis factor-α (TNF-α), transforming growth factor β-1 (TGF-β1), nuclear factor kappa B (NF-kB); depleted heme oxygenase-1 (HO-1), nuclear factor-E2-related factor-2 (Nrf2) and glutathione peroxidase (GPx) activity. Lycopene and genistein supplementation reduced liver MDA concentration, fibrosis/inflammation scores (P <0.001), alpha-smooth muscle actin (α-SMA) scores, TGF-β1, TNF-α, NF-kB (P <0.001) and collagen type 1 (P<0.01) levels in TAA-treated rats. Lycopene and genistein intake increased HO-1 (P <0.01), Nrf2 (P <0.001) and GPx activity (P<0.05) in the liver of TAA-treated groups. Lycopene combined with genistein significantly reduced fibrosis/inflammation, α-SMA scores (P <0.001), compared to the lycopene treated group. In conclusion, our results demonstrated that lycopene and genistein supplementation  protected the rat liver from TAA-caused fibrogenesis by suppressing hepatic inflammation and inhibiting HSC activation, possibly through downregulation of NF-kB and activation of Nrf2 pathways. Lycopene combined with genistein intake presented greater beneficial effects than lycopene against liver injury induced by TAA in rats.