Detoxification of carcinogens

OrganosuUur compounds have been shown to modulate the activity of glutathione -transferases (GST), a family of enzymes important in detoxification of carcinogens [24], and cytochromes P450 (CYP), a family of enzymes that activate many chemical carcinogens in experimental animals [25]. The effect of proteases inhibition is a new aspect of the biological activity of these plants and further research should be carried out to identify the specific compounds from Allium or Allium products that are responsible for this biochemical effect. 

Shimada, T. (2006) Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons. Drug Metab. Pharmacokinet. 21, 257-276. 

Epidemiological studies with dietary flavonoids have also demonstrated an inverse association with incidence of stroke (Rice-Evans 2001). Antitumour activity has been demonstrated in flavonoids. Nomilin in citrus induces glutathione-S-transferase (GST), which aids in detoxification of carcinogens. Quercetin inhibits cytotoxic... 

HD is a vesicant (blister agent) and alkylating agent producing cytotoxic action on the hematopoietic (blood-forming) tissues which are especially sensitive. The rate of detoxification of HD in the body is very slow, and repeated exposures produce a cumulative effect. It causes blisters, irritates the eyes, and it is toxic when inhaled. HD has been determined to be a human carcinogen by the International Agency for Research on Cancer. 

DeZearn MB, Oberacker DA. 1980. Detoxification of materials by microwave plasma. Safe Handling of Chemical Carcinogens, Mutagens, Teratogens, and Highly Toxic Substances 2 595-615. 

Cytochrome fcs/NADH cytochrome b reductase (human) Reductive detoxification of substituted hydroxylamine carcinogens (K = 200-400 p.M) 27-29, 50... 

Figure 15.2 Inhibition of carcinogen activation and induction of phase II detoxification enzymes by resveratrol.

Cutaneous biotransformation is mostly associated with the stratum basale layer where there can be phase I and phase II metabolism. However, the skin is not very efficient, compared to the liver. The epidermal layer accounts for the major portion of biochemical transformations in skin, although the total skin activity is low (2-6% that of the liver). Where activity is based on epidermis alone, that layer is as active as the liver or, in the case of certain toxicants, several times more active. For some chemicals, metabolism can influence absorption, and transdermal delivery systems of drugs utilize this activity. For example prodrug such as lipid esters are applied topically, and cutaneous esterases liberate the free drug. These basal cells and extracellular esterases have been shown to be involved in detoxification of several pesticides and bioactivation of carcinogens such as benzo(a)pyrene. For rapidly penetrating substances, metabolism by the skin is not presently considered to be of major significance, but skin may have an important first-pass metabolic function, especially for compounds that are absorbed slowly. 

The impact of xenobiotics on health can occur in a number of ways. As we have noted, the xenobiotic can be a carcinogen, be metabolized to a carcinogen, inhibit the detoxification of... 

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