Chemoprevention by amiloride against experimental hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats

The effects of prolonged administration of the diuretic amiloride on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) and the labeling index of the liver were investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and received s.c. injections of 2.5 mg/kg or 5.0 mg/kg body weight of amiloride every other day until the end of the experiment at week 16. Preneoplastic and neoplastic lesions staining positively for glutathione-Stransferase, placental type (GST-P) were examined immunohistochemically. In week 16, administration of amiloride at 2.5 mg/kg body weight significantly reduced the size (as mean area) of GST-P-positive lesions, and amiloride at 5.0 mg/kg body weight significantly reduced the number (as no./cm2) and sizes (as mean area and percent of parenchyma) of GST-P-positive lesions. Amiloride at both dosages also significantly decreased the labeling index of enzyme-altered lesions and amiloride at higher dosage significantly decreased the labeling index of adjacent hepatocytes. These findings indicate that amiloride inhibits hepatocarcinogenesis and suggest that this effect may be closely related to amilorideʹs inhibition of cell proliferation in enzyme-altered lesions and/or adjacent liver.