title: Squalene does not exhibit a chemopreventive activity and increases plasma cholesterol in a Wistar rat hepatocarcinogenesis model.
abstract: The eventual chemopreventive effect of squalene (SQ), a triterpene present in olive oil, was evaluated when administered to Wistar rats during a period comprising the initiation and selection/promotion of the "resistant hepatocyte" (RH) model of hepatocarcinogenesis. During 8 consecutive wk, animals received by gavage SQ (100 or 150 mg/100 g body weight) dissolved in corn oil (CO) daily. Animals treated with only CO and submitted to the RH model were used as controls. Treatments with SQ did not result in inhibition of macroscopically visible hepatocyte nodules (P > 0.05) or of hepatic placental glutathione S-transferase- positive preneoplastic lesions (PNL; P > 0.05). Hepatic cell proliferation and apoptosis indexes were not different (P > 0.05) among the different experimental groups, both regarding PNL and surrounding normal tissue areas. There were no significant differences (P > 0.05) among comets presented by rats treated with the two SQ doses or with CO. On the other hand, SQ increased total plasma cholesterol levels when administered at both doses (P < 0.05). This indicates that the isoprenoid was absorbed. Thus, SQ did not present chemopreventive activity during hepatocarcinogenesis and had a hypercholesterolemic effect, suggesting caution when considering its use in chemoprevention of cancer.
authors.affiliation: Department of Pathology, Faculty of Medicine, São Paulo State University, Botucatu, Brazil.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Scolastici
authors.forename: Thomas Prates
authors.initials: TP
authors.lastname: Ong
authors.forename: Fernando Salvador
authors.initials: FS
authors.lastname: Moreno
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D018890:Chemoprevention / Q000009:adverse effects / Q000379:methods*; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D020552:Comet Assay; D003314:Corn Oil / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007408:Intestinal Absorption; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control*; D008297:Male; D000069463:Olive Oil; D010938:Plant Oils / Q000494:pharmacology; D011230:Precancerous Conditions / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013185:Squalene / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000069463:Olive Oil; D010938:Plant Oils; D013185:Squalene; D003314:Corn Oil; D002784:Cholesterol