Lack of Inhibitory Effects of Coumaperine from Pepper on the Promotion Stage of Chemical Hepatocarcinogenesis in the Rat

Abstract

We previously indicated that coumaperine isolated from pepper can protect against the initiation of rat hepatocarcinogenesis. In the present study, potential modifying effects of coumaperine on post-initiation promotion stage were examined, using a medium term rat liver bioassay (Ito test). F344 rats were given a single intraperitoneal injection of diethylnitrosamine (200 mg/kg body wt.) and subjected to two-thirds partial hepatectomy at week 3. Commencing 2 weeks from the start, coumaperine at doses of 0, 2, 10, 50 mg/kg body wt. was given to the rats for 6 weeks. All surviving animals were killed at week 8, and their livers were immunohistochemically examined for expression of glutathione S-transferase placental form (GST-P) and transforming growth factor-α (TGF-α). The numbers and areas of GST-P positive foci in rats given 2, 10 or 50 mg/kg coumaperine were comparable to the control values. There were also no significant intergroup differences regarding numbers and areas of TGF-α positive foci. This study suggested that coumaperine does not inhibit liver carcinogenesis in the promotion stage.