A dual and opposite effect of Calendula officinalis flower extract: chemoprotector and promoter in a rat hepatocarcinogenesis model.
Calendula officinalis extracts have protective and cytotoxic effects. We previously reported the dual activity of C. officinalis in primary rat hepatocyte cultures treated with N-nitrosodiethylamine. At nM concentrations it was anti-genotoxic while at microM concentrations it exhibited genotoxic effects. Here we tested the activity of Calendula officinalis in vivo in male Fischer 344 rats initiated with N-nitrosodiethylamine, promoted with 2-acetylaminofluorene, and 70 % partially hepatectomized. Liver gamma-glutamyltranspeptidase positively altered hepatocyte foci 25 days after initiation were our end point. The protective effect of C. officinalis started at 0.1 mg/kg concentration, increased at 0.5 mg/kg and reached its maximum at 2.5 mg/kg, when it decreased the area and number of altered foci by 55 % and 49 %, respectively, in comparison with rats treated only with carcinogen. At 5 mg/kg the number and area of altered hepatocyte foci were still lower, but almost reached the figures of carcinogen-treated rats. Ten and 20 mg/kg doses produced a notorious increment in the area and number of altered hepatic foci, and at 40 mg/kg of extract the increment was 40 % and 53 %, respectively. Additionally, when 2-acetylaminofluorene was substituted by a 40 mg/kg C. officinalis extract, a promoting effect was observed with increments of 175 % and 266 % in area and number of altered hepatocyte foci with respect to controls. When N-nitrosodiethylamine was substituted by 40 mg/kg of extract, the latter did not show initiator activity. In summary, we showed a protecting activity of C. officinalis at low doses, but doses above 10 mg/kg increased altered hepatocyte foci. This dual effect is an example of the phenomenon of hormesis. Furthermore, 40 mg/kg of dry weight extract administered instead of 2-acetylaminofluorene induced a clear promoting activity. These in vivo results are similar and consistent with those reported by us in primary rat liver cell cultures.
Barajas-Farias
L M
LM
Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav), San Pedro Zacatenco, CP, México.
Pérez-Carreón
J I
JI
Arce-Popoca
E
E
Fattel-Fazenda
S
S
Alemán-Lazarini
L
L
Hernández-García
S
S
Salcido-Neyoy
M
M
Cruz-Jiménez
F G
FG
Camacho
J
J
Villa-Treviño
S
S
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020838:Calendula; D045744:Cell Line, Tumor / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D035264:Flowers; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344
D016588:Anticarcinogenic Agents; D010936:Plant Extracts