Z Gastroenterol 2004; 42 - 49
DOI: 10.1055/s-2004-826950

Nociceptin in experimentally induced hepatocellular carcinoma

A Horváth 1, A Folhoffer 1, T Csák 1, A Zalatnai 2, M Hantos 4, K Tekes 3, PL Lakatos 1, F Szalay 1
  • 11st Dept. of Int Med.
  • 21st Dept. of Pathology and Exp Cancer Research
  • 3Dept. of Pharmacodynamics, Semmelweis University, Budapest
  • 4Neurochemical Research Unit of Hungarian Academy of Sciences

Background/aim: Nociceptin (N/OFQ) is the endogenous agonist of opioid-like 1 receptor (ORL1) named as OP4. High plasma N/OFQ level has been reported in Wilson disease and in patients with hepatocellular carcinoma (HCC). We investigated N/OFQ in experimentally induced HCC.

Methods: HCC was induced in male F-344 rats by diethylnitrosamine (DEN)+Phenobarbital (PB)+carbon tetrachloride (CCl4) as published earlier. A total of 30 male F-344 rats were involved. Animals were divided into three groups. Group 1 (n=8, served as control), group 2 (n=5, treated with DEN+PB) and group 3 (n=8, treated with DEN+PB+CCl4). The animals were sacrificed at week 16. N/OFQ was measured by RIA (125I-Nociceptin kit, Phoenix Pharmaceuticals, Phoenix, USA) with minimum sensitivity of 1 pg/ml).

Results: HCC developed in each animal in group 3 at week 16 presenting also with cirrhosis, but no tumor was found in the others. In group 3 at week 16 N/OFQ was significantly higher both in the liquor (914±68.9 pg/mL) and in the plasma (91.4±4.8) than in group 2 (Li: 88.8±6,9, Pls: 9.4±0.7, p<0,001 for both) and group 1 (Li: 94.2±5,1, pls: 9.3±0.4, p<0,001). The N/OFQ content was significantly higher in the tumor tissue (463±80 fg/mg) than in the tumor free parts of the corresponding liver 59±11, p<0,01) and liver from untreated controls (36±10, p<0,01).

Conclusion: The striking elevation both in liquor and plasma nociceptin levels in rats with HCC indicates a significant alteration in N/OFQ/OP4 system. Since N/OFQ content was higher in tumor tissue than in tumor free parts of the liver and in control animals, further investigations are needed to clarify the role of N/OFQ in HCC. High plasma N/OFQ seems to be an indicator for HCC.