Lycopene improves autophagy and attenuates carbon tetrachloride-induced hepatic fibrosis in rats

Abstract

Aim To evaluate the effect of lycopene on carbon tetra-chloride (CCl4)-induced hepatic fibrosis and elucidate the underlying mechanism. Methods Male rats were randomly assigned to the control group, CCl4 group, and lycopene group. The CCl4 group was intraperitoneally injected with CCl4 twice per week for 12 weeks to induce hepatic fibrosis. The control group was intraperitoneally injected with olive oil. Lycopene was orally administered during CCl4 treatment. Body weight and liver weight were recorded. Liver function was assessed. Biomarkers of oxidative stress and inflammatory factors were measured. Histological changes and collagen expression were evaluated. The expression of TGF-β1, α-SMA, HO-1, SIRT 1, REDD1, SHP2, P62, and LC3 in the liver was determined, as well as the levels of phosphorylated NF-κB and IκB α. Results Lycopene significantly reduced the liver/body weight ratio, and AST (P = 0.001) and ALT levels (P = 0.009). It also significantly increased CAT and SOD activities (P < 0.001) and decreased MDA content (P < 0.001), IL-6 (P < 0.001), and TNF-α (P = 0.001). Histological analysis dem-onstrated that lycopene improved lobular architecture and decreased collagen expression. It also decreased the expression of TGF-β1, α-SMA, P62, and SHP2, and increased the ratio of LC3 II/I, as well as Beclin 1 and REDD1 expres-sion. In addition, it reduced NF-κB and IκB-α phosphory-lation, and elevated the levels of HO-1, SIRT 1, and PGC 1α. Conclusion Lycopene attenuates CCl4-induced hepatic fi-brosis because of its effect on autophagy by reducing oxi-dative stress and inflammation.