Abstract
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 μM 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 γ-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.
Abbreviations
DDT:1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane
DEN:N-diethylnitrosamine
AHF:altered hepatocytes foci
RH:resistant hepatocyte model
AEE:Aqueous-ethanol extract
GGT:γ-glutamyltranspeptidase
2-AAF:2-acetylaminofluorene
PH:partial hepatectomy
Key words
Antigenotoxicity - genotoxicity - promoter - chemopreventive effect - hepatocarcinogenesis -
Calendula officinalis
- hormesis
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