Cancer Letters

Cancer Letters

Volume 233, Issue 1, 20 February 2006, Pages 158-164
Cancer Letters

Chemopreventive effects of Paullinia cupana Mart var. sorbilis, the guaraná, on mouse hepatocarcinogenesis

https://doi.org/10.1016/j.canlet.2005.03.007Get rights and content

Abstract

Guaraná (Paullinia cupana) is originally from Amazon, Brazil. Its effects on mouse hepatocarcinogenesis have been investigated in this study. Mice were treated with N-nitrosodiethylamine (DEN), received three different doses of P. cupana added to commercial food, and euthanized after 25 weeks. Gross lesions were quantified, and preneoplastic lesions (PNL) were histologically measured. Cellular proliferation was evaluated by immunobloting for the proliferating cell nuclear antigen (PCNA). The incidence and multiplicity of macroscopic lesions were reduced. The PNL number and PCNA expression were reduced in the highest P. cupana dose. According to these results, guaraná presented inhibitory effects on DEN hepatocarcinogenesis in mice.

Introduction

Paullinia cupana (the guaraná), belongs to the Sapindaceae family and it is original from Amazonia, Brazil where the Saterê-Maué Indians [1] have used it for many years as a stimulant. It is used in the composition of several phytoproducts, like non-alcoholic beverages, tonics, anti-stress capsules and others. Some properties of P. cupana have already been scientifically shown, like weight loss [2], stimulation of central nervous system [3], maintenance of memory [3], blood ‘thinning’ [4] and possible aphrodisiac property [5].

The guaraná extract presents some compounds like methyl-xanthines such as caffeine, theobromine and theophyline, also occurring tannins, saponins, catechins, epicatechins, proanthocyanidols and other compounds in minor concentrations [6]. Tannins can reach 16% in dry matter, and caffeine varies from 2.5 to 5% [6]. Phytochemicals can modulate the process of carcinogenesis blocking the adverse effects of carcinogenic agents, or suppressing the malignant transformation of preneoplastic cells [7]. For instance, the green tea (Camelia sinensis) has some substances like epigallocatechin gallate, which has demonstrated chemopreventive effects in various studies [8], [9], [10] and also as an adjuvant in chemotherapy [11], [12]. There are many similar substances both in tea and guaraná, particularly substances from the polyphenolic class. Taking into account these facts, does guaraná present chemopreventive effects?

In-vitro studies evidenced that the anti-oxidant effects of P. cupana are related to the inhibition of spontaneous oxidative processes, probably due to a high concentration of tannins [13]. Some tannins have been shown to protect DNA from lesions by benzopyrene [14]. There were different possible pathways describing the action of the poliphenols in controlling the carcinogenesis specially related to genomic stability [15].

Besides several studies about plants related to cancer chemoprevention, to our knowledge there are no studies investigating the chemopreventive effects of this Brazilian plant. The aim of this study was to verify the effects of guaraná, supplied in three different doses: 0.1, 1.0 and 2.0 mg P. cupana/g BW (milligram of P. cupana per gram of body weight) on mouse hepatocarcinogenesis.

Section snippets

Animals

BALB/c female mice were used. They were maintained at the animal facility from the Department of Pathology of the Faculty of Veterinary Medicine and Animal Science, University of São Paulo. Animals (five per cage) were housed in polycarbonate cages, and maintained under controlled conditions of temperature (20±4 °C), and relative humidity (45–65%), with a 12 h-light/dark cycle.

Paullinia cupana

The P. cupana powder was kindly supplied by EMBRAPA, Amazônia Ocidental (Agropecuary Research Brazillian Enterprise) and

Food consumption, body weight, body weight gain, liver weight and relative liver weight in P. cupana treated animals

The food consumption, body weight, body weight gain, liver weight and relative liver weight of animals submitted to this experiment showed no difference from the control group (data not shown).

Effects of P. cupana on gross lesions

Effects of P. cupana on gross lesions are shown in Table 2. After macroscopic evaluation, animals that received control diet showed a 100% incidence of lesions. The other groups showed minor incidence of gross lesions when compared with control, and the animals treated with 2.0 mg P. cupana/g BW (D) showed

Discussion

By definition, chemoprevention of cancer is a means of cancer control in which the occurrence of this disease is prevented by administration of one or several chemical compounds [18], interfering beneficially in the carcinogenic process [19]. The chemoprevention of cancer can be classified as: primary prevention or preventing the induction of cancer in healthy animals; secondary prevention or preventing cancer in patients that have pre-malignant alterations; and tertiary prevention or

Acknowledgements

These experiments were made at the level of scientific initiation by Heidge Fukumasu, who was the recipient of a fellowship from FAPESP (Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil, process number 02/02736-0). The study has been supported by CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil).

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