Effects of wasabi (Wasabia japonica) rhizome and its main bioactive compound, allyl isothiocyanate, on the early stages of fibrosis-associated hepatocarcinogenesis.

Abstract

The poor prognosis of fibrosis-associated hepatocellular carcinoma (HCC) encourages preventive strategies. The wasabi rhizome (Wasabia japonica) - of the Brassicaceae family - is widely used as an ingredient in culinary, and is rich in bioactive compounds, including the abundant allyl isothiocyanate (AITC). Although other wasabi isothiocyanates showed beneficial effects on HCC in vitro, the implications of this in natura food in in vivo models are unknown. Thus, we evaluated whether wasabi rhizome or AITC attenuates the early stages of fibrosis-associated hepatocarcinogenesis. Male C57BL6/J mice were submitted to a chemically induced hepatocarcinogenesis model, receiving diethylnitrosamine (DEN) carcinogen, and multiple fibrogenic thioacetamide (TAA) cycles. Concomitantly to TAA (6 wk), the animals received by intragastric administration (5×/wk) daily prepared wasabi rhizome extract (0.5 or 1.0 g/kg body weight [bw]) or AITC (2 mg/kg bw, in 0.2% wasabi rhizome proportion). Both wasabi and AITC did not modify the alterations in body and organ weights, and serum biomarkers (ALT, AST, and urea) induced by DEN/TAA regimen used. The DEN/TAA-mediated increase in liver inflammation/fibrosis (collagen area, scores, p65 protein) and liver preneoplastic foci burden remained unaltered after wasabi/AITC interventions. In addition, AITC had minor effects on attenuating the DEN/TAA-mediated effects in pro-inflammatory CD68+ cells and antioxidant capacity in the liver. In vitro, AITC reduced the viability of collagen-producing hepatic stellate cells, while no major effects were observed in vivo. In summary, wasabi and AITC exert minor effect on the early stages of fibrosis-associated hepatocarcinogenesis, while it seemed to be safe food ingredients in doses tested herein.