Efeito do ácido ascórbico durante a hepatocarcinogênese quimicamente induzida em ratos

Abstract

Studies in animal models suggest that vitamins acting as antioxidants may have a protective effect in carcinogenesis; ascorbic acid seems to be one of the most effective on a wide variety of experimental neoplasias. The present research has verified the effect of ascorbic acid in rat hepatocarcinogenesis. Thirty male rats were used, distributed in 3 groups (DEN+AA, DEN and AA) with 10 rats each. The experimental protocol corresponded to that one of Solt modified: initiation with 200mg/kg diethylnitrosamine, i.p.; promotion procedure for 6 days per os, between days 18 and 24, with acetylaminofluorene (30mg/Kg) and carbon tetrachloride (2mL/Kg) in the 21st day. Ascorbic acid (4% solution) was offered continually in the drinking water starting one week before the initiation. At week 8, blood of half of the animals of each group was collected by heart puncture under sedation (ether inhalation), being afterwards euthanized by cervical displacement. Serum was immediately frozen in liquid nitrogen and maintained at -80°C until the moment of gama-glutamyltranspeptidase dosage. The liver of each animal was collected, weighed, described grossly, photographed, fixed in 10% buffered formalin, and processed for histopathology. Remaining animals stayed without any treatment during 4 months, when they were euthanized. At week 8, the gammaglutamyltranspeptidase serum concentration was higher in DEN group, being significantly different from AA group. The relative liver mass was similar among the groups. Liver gross pathology showed multiple white-grayish nodules measuring 1-5mm only in animals of DEN group. Microscopic analysis revealed phenotypically altered foci and nodules in animals of groups DEN+AA and DEN; nodules were very frequent and prevalent in DEN group. No altered foci and nodules were observed in animals of AA group. The nuclear volume of hepatocytes in altered foci and nodules was similar among the groups. The number and the area of glutathione-S-transferase positive foci and nodules in animals of DEN+AA and DEN groups were significantly larger than in AA group. At week 24, the relative liver mass in animals of DEN was significantly larger than the other groups. Liver gross pathology showed congestion and multiple white-grayish nodules measuring 1-5mm only in animals of DEN group. Microscopic analysis revealed phenotypically altered foci and nodules in all groups; nodules were frequent and prevalent in DEN group. The nuclear volume of hepatocytes in altered foci and nodules was similar among the groups. The number and the area of glutathione-S-transferase positive foci and nodules in animals of DEN+AA and DEN groups were significantly larger than in AA group, however the group DEN+AA was significantly inferior to DEN group. The tumor incidence was higher in DEN group. The ascorbic acid has a protective effect on the hepatocarcinogenesis induced in rats