Chemopreventive effect of orange oil on the development of hepatic preneoplastic lesions induced by N-nitrosodiethylamine in rats: an ultrastructural study

Indian J Exp Biol. 2002 Mar;40(3):245-51.


Orange peel oil is used extensively as an approved flavour enhancer in fruit drinks, carbonated beverages and as a scenting agent in soaps and cosmetics. Limonene, which is a monocyclic monoterpene is present in orange peel oil from 90 to 95% (w/w). Monoterpenes have been shown to be very effective chemopreventive agents against several rodent tumors and are currently in clinical trials. However, not much information is available regarding the ultrastructural changes associated with the chemopreventive effects of the monoterpenes. The effect of orange oil on the suppression of preneoplastic hepatic lesions during N-nitrosodiethylamine (DEN) induced hepatocarcinogenesis was studied electron microscopically. Rats were administered 200 ppm DEN through drinking water for a period of 1 month. After an interval of 2 weeks, the animals were administered orange oil by gavage for a period of 5 1/2 months. The chemopreventive effect of orange oil was monitored on the basis of liver weight profile, histological pattern by light microscopy and ultrastructural alterations by electronmicroscopy. Orange oil administration following DEN treatment showed decreased liver weights, increased intercellular gap junctional complexes, cell density and polarity when compared with only the DEN treated rats. In the present study chemopreventive effect of orange oil on DEN-induced hepatic preneoplasia in rats which is associated with the restoration of the normal phenotype and upregulation of junctional complexes has been demonstrated.

MeSH terms

  • Animals
  • Carcinogens / toxicity
  • Diethylnitrosamine / toxicity
  • Gap Junctions / drug effects
  • Gap Junctions / ultrastructure
  • Liver / drug effects
  • Liver / pathology
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / prevention & control*
  • Liver Neoplasms, Experimental / ultrastructure
  • Male
  • Microscopy, Electron
  • Organ Size / drug effects
  • Plant Oils / pharmacology*
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / prevention & control*
  • Precancerous Conditions / ultrastructure
  • Rats


  • Carcinogens
  • Plant Oils
  • Diethylnitrosamine
  • orange oil