Preventive Effect of Geraniol on Diethylnitrosamine-Induced Hepatocarcinogenesis in Rats

[ABSTRACT] [Background] Geraniol is a plant-derived phytochemical possessing anti-cancer action. The anti-carcinogenic effect of geraniol was investigated in the diethylnitrosamine (DEN)-induced hepatocarcinogenic rat model. [Methods] Male Wistar rats were intraperitoneally injected with 300 μL of phosphate-buffered saline (PBS) (G1; n = 4) or DEN (100 mg/kg body weight) dissolved in PBS (G2; n = 8) every 2 weeks on experimental weeks 2, 4 and 6. The rats were treated with a low concentration (0.07%) of geraniol (G3; n = 9) and high concentration (0.35%) of geraniol (G4; n = 7) for 12 weeks. To evaluate the effects of geraniol on the DEN-induced hepatocarcinogenesis, we compared the relative liver weight, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels and expression levels of proliferating cell nuclear antigen (PCNA) and glutathione S transferase-P (GST-P) by immunohistochemical analyses among each group. [Results] Relative liver weight was significantly higher in G2 than in G1 (P < 0.01). Both serum AST and ALT levels were significantly higher in G2 than in G3 and in G4 (P < 0.05). Serum ALP levels did not show a significant difference among each group. Percentages of both PCNA- and GST-P- positive area were significantly decreased in G3 and in G4 compared to in G2 (P < 0.001, respectively), suggesting anti-hepatocarcinogenic effects of geraniol. [Conclusion] Geraniol is a promising compound useful for suppression of hepatocellular carcinoma. The mechanisms of action are required to be clarified in the future intensive study.