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Year: 2006  Vol. 10   Num. 4  - Out/Dez - (6º) Print:
Section: Original Article
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Mate (Ilex Paraguariensis) as an Etiological Agent of Neoplasia in the Aerodigestive Tract. An Experimental Study
Author(s):
Geraldo Pereira Jotz1, Honório Sampaio Menezes2, Claudio Galleano Zettler2, Rafael José Vargas Alves3, Roberto Chacur4, Caroline Buzzatti4, Mariana Dias de Oliveira4, Tiago Hermes Maeso Montes5, Marta Hübner6, Eduardo Walker Zettler6
Key words:
Mate. Cancer. Esophagus. Lung. Pharynx. Trachea.
Abstract:

Background: There are studies that consider drinking "chimarrão" (an infusion of mate, Ilex paraguariensis) a risk factor for developing oropharynx, esophagus and larynx cancer. Aim: To make a histological comparison between the aerodigestive tracts of a group of rats submitted to the consumption of erva-mate Ilex paraguariensis, with a control group. Methods: Seventy-five adult Wistar rats were tested, 60 drinking mate at room temperature and 15 drinking water (control group), during a period of 5 months. The histology of the aerodigestive tracts of these animals was analyzed. Results: The animals presented alterations in the anatomical-pathological exams. There was a significant difference (p=0.02) between those that were given mate and the control group. Conclusion: There is evidence to suggest that the consumption of mate affects the upper aerodigestive tract in the animals studied, but not inducing cancer.

INTRODUCTION

The habit of drinking mate, or "chimarrão", as this drink is also called, by hot infusion, made of cut and dry leaves of Ilex paraguariensis, has been indicated as a possible cause of cancer in the aerodigestive tract in South America, where high incidence rates are noticed in an area that includes the south of Brazil, Uruguay and the northeast of Argentina.

Such habit is frequent in areas with higher incidence of esophagus cancer and it is not frequent in other areas with lower incidence (1).

Munoz et al. (1) described a case-control case which showed an association of epidermoid carcinoma of the esophagus with alcohol, tobacco, meat and mate ingestion.

Victora et al. (2) described a relative risk 12.2 times higher to develop esophagus cancer for drinkers of more than 2.5 liters of mate per day. The two possible mechanisms are involved in the rising of risks for esophagus cancer, the first would involve carcinogenic substances in the plant extract and the second would involve the thermo injury increasing the action of other ingested carcinogenic substances. (2)

The thermo injury has been studies in Paraguay (3), in Japan (4), in Iran (5), in the Soviet Union (6) and in Puerto Rico (7), which suggests an association between the ingestion of hot drinks and the development of esophagus cancer, which makes one suspect that the high temperature in which it is drunk, that is, 69,5 ºC (2,8) may increase the carcinogenesis, specially when associated to alcohol and tobacco.(9)

Mate is also used by the popular medicine for losing weight, as a simulator of the nervous central system, diuretic and antirheumatic (10).

The present study aims at evaluating the ponderal weight and the histology of the aerodigestive tract in rats which were undertaken to the consumption of mate at room temperature, comparing with a group that received only water during the period of study, just analyzing the effect of the product, without its thermo effect.


MATERIAL AND METHODOLOGY

The study was experimental, using a population of 75 adults Wistar rats (250-300g), divided into 3 groups of 20 rats each, which consumed a mate substance (with leaves of kind 1) with water at room temperature during 5 months, and a group of 15 rats which consumed water without mate, as a control group, whose aerodigestive systems were analyzed with anatomopathologic exam (hematoxiline-eosine and immunohistochemical - Ki67 and p53), at the eight months old.

The groups ingested the drink at room temperature, but it was prepared with hot water at the standard model of traditional chimarrão (grounded mate leaves). Each study group consumed one kind of mate: Group 1, green mate (a product with great quantity of thin granules, which keeps the bitter taste and is used for the consumption of chimarrão, presenting green coloring and foam. Such product is the favorite one by the citizens of the state of the south of Brazil. Group 2, Mate pure leave (export mate, which has a very low quantity of sticks; it is undertaken to a rest and aging process during storage, making a less green and softer product, according to the taste of the foreign market). And Group 3, Mate in natura (a product which is elaborated by researchers with leaves of controlled origin, with an intermediate grounding between the two previous products)

Three-month-old rats are considered adults, and 8-month-old ones are considered old. Hat being the case, this period of 5 months has been chosen in order to better simulate the human consumption. Besides consuming mate, the rats also consumed "Nuvilab®", which is a special rat food for its species. The same kind of rat food was provided to the control group.

Both the consumption of mate (A®, B® e C® brands; groups 1, 2 and 3, respectively) and the food ingestion were controlled daily. It is necessary to point out that the mate of C brand is of known and controlled plantation (in natura).

After the rats' euthanasia, the histological study of tissues from the aerodigestive tract was performed, including trachea, lungs, tongue, pharynges, esophagus, stomach, duodenum and pancreas. The obtained material was processed in histotechnic with confection of paraffin blocks, with microtome cuts at 5 micras large. Three cuts have been obtained, being the first paraffin and using the coloring through the hematoxiline and eosine method. The two following ones were obtained in organosilanus for immunohistochemical study of p53 and ki67 antibodies.

Ethical Aspects

The animals have been treated according to the law number 6638 dated from 1979 and according to the Manual for bioterium technicians, which regulates and indicates minimum and honorable cares for experiment animals, as well as to orientations stated by the Colégio Brasileiro de Experimentação Animal (COBEA) (Experiment Animal Brazilian Council). The registration has been approved by the Ethics Committee in Research in of both institutions that housed the experiment.

Statistical Analysis

For data registration and analysis, the SPSS system has been used. The results have been expressed in descriptive statistics, and the Fischer and qui-square tests have been used. The alpha limit considered in these comparisons will be of 5 %, with alpha significance level of 0.05.


RESULTS

The control over 60 rats which received mate daily and the control group of 15 rats, followed by anatomopathological exams of the aerodigestive tract, provided the folleoing results: Tongue and oropharyges have not presented any relevant histological alterations.

The Table 1 reveals the results of the exams to which the pieces have been undertaken.




The animals presented alterations in the anathomopathological exams (Table 1), presenting significant difference (p=0.02) between the ones which have consumed mate and the control group. Only one malign tumor has occurred (Mediastinum Mesothelioma) among the animals which consumed mate, related to the mediastinu, being an occasional finding. The respiratory tract has been the most affected one, and a great number on inflammatory respiratory alterations have been observed (tracheitis, bronchelitis, chronical tracheitis, trachea scaly metaplasia, pneumonia, trachea glandular hyperplasia and pleural fibrosis).

The variation in body weight has been noted and the results have been demonstrated on Table 2.




Group 1 had an average ponderal gain of 13.87% (SD=6.49), Group 2 of 15.69% (SD=3.78), Group 3 of 23.65% (SD=14.33) and the control group 44.08% (SD=5.82). There was a statistical difference between the study groups and the control group (p<0.001) and the difference between the group that used the mate of C brand (in natura) and the groups that used the commercial mate (A and B) was p<0.03.


DISCUSSION

This project evaluated the histological and weight differences of aerodigestives tracts of rats which were undertaken to the consumption of mate Ilex paraguariensis, ingested at room temperature, eliminating the high temperature of water confusion factor, once such fact is stated as a risky factor for the development of cancer on mate drinkers.(11)

Among the risky factors for the malign neoplasia of the digestive tract, mate (the habit of taking chimarrão) has been referred as an important factor in the medical literature. One factor about which a consensus has not been reached in the literature is the quantity of digested mate, as well as the previously mentioned temperature of the infusion. However, as hot liquids have not been used, the temperature factor has been forgotten.

The mouth, larynges, oropharynges cancer in mate drinkers has high predominance in Uruguay(12) and in the south of Brazil(13), presenting a double risky factor comparing to people who do not drink mate. When risky factors such as alcohol (wine) and tobacco were associated, the risky factor raised five times (14). The tongue cancer has been studied in Uruguay(15) where the risky is of 2.5 among the mate drinkers. In the mouth and oropharynges cancer there is the local heat factor in the origin of skin alterations, once in our study we were not able to demonstrate the mate had carcinogenic potential, not discarding, however, the possible effects related to their long-term exposition.

There is high incidence of esophagus cancer in areas where the habit of drinking mate is predominant, such as Uruguay and south of Brazil. Victora et al. (17) have found a 1.9 risk rate of esophagus cancer development in mate drinkers if compared to non-drinkers. Vassalo et al. (16) stated that mate contains tannin, which are responsible for the increase of esophagus cancer.

Rolon et al. (18) , Castellsague et al. (19) studied the relation between esophagus cancer and drinkers of hot mate, not relating to the habit of drinking it cold, indicating the very hot water as an arousing risky factor of esophagus cancer, a fact that has not been confirmed by other researchers such as De Stefani et al. (20) e Pintos et al. (13) . However, we have not observed in our study any alteration in the anatomopathological exam of the digestive tract, showing that as we remove heat as a risky factor, the kinds of mate which have been studied were not seen as harmful to the tissue.

Munoz et al. (1) histologically confirmed the occurrence of esophagitis in mate drinkers, a fact which has not been found in our samples.

Although the thermo injury has been suggested as an action mechanism, the chemical carcinogenesis of mate has not been excluded yet, once it is observed in the literature that many authors indicate the mate itself contains a carcinogenic and mutagenic intrinsic component, not taking into account the hot infusion and the final product (1,14,18, 21). Also, the fenatrenic derivates, including benzopirenum, have already been identified in the chemical fractions of mate. These substances have been considered carcinogenic in animal laboratories, when purified and applied on their skin (16,22).

In in vitro study, Fonseca et al. (21) found genotoxic and mutagenic mate extracts, as well as inductors of chromosomal aberrations in peripherical lymphocytes which were treated with mate. Such components found in mate may be responsible for the increase of risk of lung cancer observed in control-case study in Uruguay (23). The present study contains evident pathological alterations in the tissues of the aero tract (trachea, bronchium and lungs), probably due to the indirect actions of those substances, once there is a significant difference between the groups of rats that ingested mate and the control group.

In the literature, we have not found any data about the carcinogenicity of mate ingestion by experiment animals (11). However, in our study we have found a rat which had neoplasia (mesothelioma of mediastinum) among the ones which have ingested mate, being the only viscera with neoplasic alterations, which does not discard the hypothesis that we combine mate ingestion to other risky factors, it produces a cancer potential effect, as the fact stated by Stefani et al. (24), which justifies the high bladder cancer rate in Uruguay. Besides, the exposure to this kind of herb (Kind 1), as well as the three brands studies, do not enable us to affirm that mate ingestion does not have carcinogenic effects.

The weight loss (or little weight gain) of animals is according to the expected effect for the mate ingestion, as Gosmann et al. (10) states, probably due to its diuretic and stimulator (of the central nervous system) effect. However, in this study we have only used mate of kind 1 and, if we compare the commercial mates (A, B, C) among them and between the control group, we may observe significant difference in relation to the ponderal weight, with meaningfully higher difference in the control group. If we compare mates, we observe significant difference (p<0.03) between the group which used the brand C (natura) and the groups which used commercial herb (A and B), which proves the diuretic factor of some commercial herbs, higher than others.

The study which has been performed here eliminated confusion factors and analyzed a long period of life of experiment animals, in which mate has been prepared according to the local costumes and left to cooling. What could be eventually modified is the infusion concentration and the number of animals used.


CONCLUSION

Ccording to the presented studies it is possible to conclude that animals that ingested the mate infusion presented alterations in the aerodigestive tract in the anatomopathological exams, in which there was an statistically significant difference between them and the control group. Only one malign tumor has occurred (Mediastinum Mesothelioma) among the animals which consumed mate, related to the mediastinum, being an occasional finding. The infusions prepared with mate significantly reduced the gain of weight in rats that ingested mate in relation to the control group, during the study period.


ACKNOWLEDGEMENTS

We thank Antonio Rios for the logistic support in the treatment of animals.


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1. DR (ORL e CCP) at UNIFESP (Otorrinolaryngology Chief Department and Head and Neck Surgery department Universidade Luterana do Brasil)
2. Doctor in Medicine (Professor at ULBRA)
3. Medical Student - ULBRA
4. Medical doctor
5. Medical Student - ULBRA
6. Medical Student - ULBRA
7. Doctor (Professor at ULBRA)

Universidade Luterana Do Brasil
Rua Dom Pedro II 891 conj. 604 Porto Alegre - RS Cep 90550-142

This article was submitted to SGP - Sistema de Gestão de Publicações (Publication Management System) from RAIO on August 8, 2006 and was approved on September 26, 2006 21:49:50.
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