Piperine prevents N-nitrosodiethylamine-induced hepatocarcinogenesis via modulating oxidative stress and gap junction

Phytochemicals are shown to exhibit strong chemopreventive potential which is mediated by simultaneously targeting oxidative stress and different cellular pathways. In this study, we investigated modulatory effect of piperine in N-Nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. Study was conducted at 2 stages of hepatocarcinogenesis: initiation stage (after 24 h of NDEA administration) and progression stage (after 20 weeks of NDEA administration). Hepatocarcinogenesis mouse model was developed by administration of NDEA intraperitoneally (200 mg/kg bw, cumulative dose) at weekly intervals to male BALB/c mice. Piperine was administered orally (50 mg/kg bw, dissolved in corn oil) weekly twice, till completion of the study. The protective effect on piperine in NDEA-induced liver damage was evident during initiation phase of the study as piperine treatment normalized liver injury markers, ROS levels and modulated carcinogen biotransformation enzymes. During progression stage of carcinogenesis, piperine treatment showed decreased tumor incidence and multiplicity. The dielectric parameters of the tumors also indicated impeded tumor progression. Gap junction expressions deteriorated and modulated during carcinogenesis was normalized by piperine treatment. In conclusion, piperine showed significant protection against hepatocarcinogenesis both at initiation and progression stage.