Investigation of the effects of embelin on diethylnitrosamine-induced liver damage in rats

Diethylnitrosamine (DEN) has strong teratogenic, mutagenic and carcinogenic effects. Embelin is the compound isolated from the dried fruits of Embelia ribes (Vidanga-false black pepper) plants. In this study, the possible effects of embelin (E) on biochemical and histopathological parameters and gene expression levels in rats with liver damage induced by DEN were investigated. Twenty-eight three-month-old Wistar albino male rats were divided into four groups as sham, E, DEN and DEN + E groups. A single dose of 200 mg/kg DEN was injected intraperitoneally into the DEN groups, and 1.2 mg/kg embelin was injected intraperitoneally into the E and DEN + E groups for 14 days. Liver enzymes and lipid profiles, total antioxidant capacity (TAS) and total oxidant capacity (TOS) levels were measured from serum samples. Sonic hedgehog (Shh, Ptch, Smo, Gli1), inflammatory (Tnfa, Il6, Il1b) and apoptotic (Tp53, casp3, Bcl2, Bax) genes were analyzed in liver tissue using RT-PCR method. Liver tissue samples stained with hematoxylin and eosin were examined under light microscope. Administration of DEN to rats increased serum liver enzyme, lipid and oxidant capacity levels and expression of genes in the inflammatory, apoptotic and Shh signaling pathways. Additionally, an increase in congestion, degeneration, fibrosis, inflammation, apoptosis, Kupffer cell count and bile pigment accumulation was observed in the DEN group, and these histopathological changes were significantly reduced by treatment with embelin. Embelin decreased liver enzyme and lipid levels, increased the activity of TAS, which is an antioxidant capacity, decreased the gene expression levels of proinflammatory cytokines Tnfa, Il6 and Il1b, and the activation of the Shh signaling pathway. It also increased the expression of Bcl2 and decreased the gene expression levels of Tp53, Casp3 and Bax, and inhibited liver apoptosis. In conclusion, embelin may have a therapeutic effect on DEN-induced liver damage by inhibiting oxidative stress, inflammatory and apoptosis response, regulation of the Shh pathway, regulating liver functions and preventing degenerative disorders in the liver.