A Dual and Opposite Effect ofCalendula officinalisFlower Extract: Chemoprotector and Promoter in a Rat Hepatocarcinogenesis Model

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 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.

Perfil de polifenoles, capacidad antioxidante y efecto citotóxico in vitro en líneas celulares humanas de un extracto hidroalcohólico de pétalos de Calendula officinalis L.

“…Besides, the results from this paper also correlate with a previous study reporting that a Calendula officinalis extract with potent in vitro cytotoxic activity, may be further supported by their experimental results were in vivo models in which rats were treated with 40mg/kg for day in period for 34 days showering reduction diameters of tumors, interpreted as antitumor activity (Barajas Farías et al, 2006).…”

Enhancedin vitroandin vivoantioxidant activity and mobilization of free phenolic compounds of soybean flour fermented with different β-glucosidase-producing fungi

“…At the end, there is a doubt about the role of flavonoids present in fruits and vegetables as a disease-protective and if this protection is due to their antioxidant effects (Halliwell 2007). Indeed, although studies in cell cultures indicate that phenolic compounds have antioxidant activity, Barajas-Farias et al (2006) reported results with Calendula officinalis extracts where they show antigenotoxic effects in nmol l )1 concentrations and genotoxic effects in lmol l )1 concentrations.…”

Aqueous crude extract of Rhoeo discolor, a Mexican medicinal plant, decreases the formation of liver preneoplastic foci in rats

“…The groups of altered hepatocytes have elevated levels of detoxification enzymes such as ␥-glutamyl transpeptidase; therefore, this enzyme has been employed as a tumor marker (Semple-Roberts et al, 1987;Hanigan, 1998). The antitumoral capacity of some plants described as curative has been demonstrated experimentally, i.e., Ardisia compressa and Calendula officinalis (González de Mejía et al, 2004;Barajas-Farías et al, 2006). Rhoeo discolor L. Hér Hance [syn.…”