Phytoestrogens toxicity

ROTH A, scHAFFNER w and BERTEL c (1999) Phytoestrogen kaempferol (3,4, 5,7-tetrahydroxyflavone) protects PC 12 andT47D cells from beta-amyloid-induced toxicity. JNeurosci Res. 57 (3) 399-404. 

SHEEHAN D M (1998) Herbal medicines, phytoestrogens and toxicity risk benefit considerations. Proc Soc Exp Biol Med. 217 (3) 379-85. 

Assessment of whether a chemical has the potential to cause adverse effects in humans arises usually from direct observation of an effect in animals or humans, such as the acute poisoning episodes that have occurred when potatoes contain high levels of glycoalkaloids. Epidemiological studies have also been used to infer a possible relationship between intake of a particular type of food, or constituent of that food, and the potential to cause an adverse effect. Such observations led to the characterisation of the aflatoxins as human carcinogens. However, natural toxic substances that occur in plant foods have often been identified through observations in animals, particularly farm animals. It was observations of adverse effects in farm animals that led to the further characterisation of the phytoestrogens and the mycotoxins. In other instances, the concern arises from the chemical similarity to other known toxins. 

Wiseman H. Dietary phytoestrogens, oestrogens and tamoxifen mechanisms of action in modulation of breast cancer risk and in heart disease prevention. In Biomolecular Free Radical Toxicity Causes and Prevention (H Wiseman, P Goldfarb, TJ Ridgway, A Wiseman, editors) John Wiley, Chichester, pp. 170-208, 2000. 

There are considerable data on the chronic toxicity of NP in laboratory animals. The focus of these investigations has typically been evaluation of the potential reproductive and developmental effects of NP, due to its ability to modulate estrogen receptor-mediated responses. Many endpoints are not consistently observed across studies. Some of this variability may be due to differences in the conditions, design, and other test-specific variables of the toxicity tests. For example, since phytoestrogens are abundant in most laboratory animal feeds (such as found in soy and alfalfa) and are known to modulate estrogen receptor-mediated responses, phytoestrogens may be confounding factors as a result of the feed selection. 

Once the benefits of a key component in food are documented, the challenge is to increase its concentration, and presumably its benefits, while maintaining safety. For example, isoflavones in soy are phytoestrogens with a chemical structure similar to estrogen. Isoflavones may reduce cholesterol, but what is the risk of increasing the intake of a compound that may modulate estrogens Knowledge of the toxicity of functional food components is crucial to improve their benefit-risk ratio. The efforts... 

Several cases of hepatotoxicity associated with chaparral use have been described (see Section 16.5). The mechanism of chaparral-associated hepatotoxicity is unknown. It is not known if chaparral is an intrinsic hepatotoxin (i.e., toxic to everyone if the dose is sufficient) or an idiosyncratic hepatotoxin (i.e., toxic only to those who have certain genetically aberrant metabolic pathways or immune system defects). Proposed mechanisms of chaparral-associated hepatotoxicity include (1) inhibition of cyclooxygenase or cytochrome P-450, (2) an immune-mediated reaction, (3) formation of a toxic metabolite, (4) impairment of liver function by phytoestrogens found in chaparral, and (5) cholestatic mechanisms causing impairment of bile formation or excretion. There is likely overlap between the two categories and the various mechanisms. In addition, toxicity may be influenced by age, weight, nutritional status, exposure to other drugs and chemicals, cumulative dose, and preparation (i.e., tea, dried plant parts, etc.) (Sheikh et al., 1997). 

Lamp>e JW, Chang J-L. Interindividual differences in phytochemical metabolism and disposition. Semin Cancer Biol. 2007 17 347-353. Setchell K, Adlercreutz H. Mammalian lignans and phytoestrogens. Recent studies on their formation, metabolism, and biological role in health and disease. In Rowland IR, ed. Role of the Gut Flora in Toxicity and Cancer. London Academic Press 1988 316—345. 

Wang, C.N., Chi, C.W., Lin, Y.L., Chen, C.F., and Shiao, Y.J. 2001. The neuroprotective effects of phytoestrogens on amyloid beta protein-induced toxicity are mediated hy abrogating the activation of caspase cascade in rat eortieal neurons. The Journal of biological chemistry, 276(1), 5287-95. 

Clarke, D.B., Barnes, K.A., Castle, L, Rose, M., Wilson, L.A., Baxter, M.J., Price, K.R., and DuPont, M.S. 2003. Levels of phytoestrogens, inorganic trace-elements, natural toxicants and nitrate in vegetarian duplicate diets. Food Chem 81, 287-300. 

Isoflavones have been found in higher concentrations only in the legume family of plants (Fabaceae) and occur in significant amounts only in soybeans and soya bean products. Isoflavones exhibit oestrogenic activity, but also further toxic effects, and are often classified, together with other active compounds, as phytoestrogens (see Section 10.4). 

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