Placenta damage

Caffeine and almost all of its metabolites cross the placenta and diffuse into virtually all fetal tissues.12 Caffeine has been shown to produce chromosomal damage in mammalian cells.3 There is an increase in fetal mortality and morbidity when pregnant rats are fed caffeine in increasing doses.4... 

One of numerous examples of LOX-catalyzed cooxidation reactions is the oxidation and demethylation of amino derivatives of aromatic compounds. Oxidation of such compounds as 4-aminobiphenyl, a component of tobacco smoke, phenothiazine tranquillizers, and others is supposed to be the origin of their damaging effects including reproductive toxicity. Thus, LOX-catalyzed cooxidation of phenothiazine derivatives with hydrogen peroxide resulted in the formation of cation radicals [40]. Soybean LOX and human term placenta LOX catalyzed the free radical-mediated cooxidation of 4-aminobiphenyl to toxic intermediates [41]. It has been suggested that demethylation of aminopyrine by soybean LOX is mediated by the cation radicals and neutral radicals [42]. Similarly, soybean and human term placenta LOXs catalyzed N-demethylation of phenothiazines [43] and derivatives of A,A-dimethylaniline [44] and the formation of glutathione conjugate from ethacrynic acid and p-aminophenol [45,46],... 

Infants are protected during gestation because the placenta clears most potential toxins. The classical form of the disease therefore does not become clinically manifest until a few days after birth. An initial phase of alternating irritability and lethargy progresses over a period of days to frank coma and respiratory embarrassment. Irreversible brain damage is common in babies who survive, particularly those whose treatment is delayed until after the first week of life. 

Distribution, including accumulation of an absorbed substance, will be the same irrespective of the route of administration. However, distribution and accumulation at the site of apphcation (inhalation, oral, dermal) may depend on the route of administration. In such cases, local accumulation may occur and may be responsible for tissue damage. In these cases, systemic toxicokinetics of the substance may be of limited relevance for the risk assessment. It is generally not cmcial for risk assessment to determine the precise tissue distribution profile for a substance. In certain special cases, however, specific tissue distribution studies may assist or even be essential for the interpretation of available toxicological data. For example, it may be of interest to know whether the substance will cross the blood-brain barrier, the placenta barrier, or will accumulate in specific tissues. 

Thus, in vitamin E deficiency, selenium has a beneficial effect in lowering the concentrations of alkylperoxyl radicals, and conversely, in selenium deficiency, vitamin E has a protective effect in reducing the radicals. When selenium is adequate, but vitamin E is deficient, tissues with low activity of glutathione peroxidase [e.g., the central nervous system and (rat) placenta] are especially susceptible to lipid peroxidation, whereas tissues with high activity of glutathione peroxidase are not. Conversely, with adequate vitamin E and inadequate selenium, membrane lipid peroxidation will be inhibited, but tissues with high peroxide production and low catalase activity will still be at risk from peroxidative damage, especially to sulfhydryl proteins. 

Cisplatin and related compounds cross the placenta and can therefore cause fetal damage. Cisplatin is teratogenic in mice and embryotoxic in mice and rats. The platins should only be used during pregnancy in life-threatening situations. The patient should be informed of the potential hazard to the fetus (263). 

Animal studies suggest that exposure to bay-region polycyclic aromatic hydrocarbons can damage the hematopoietic system leading to progressive anemia as well as agranulocytosis. Subcutaneous injection of 5 mg benz[u]anthracene daily to rats from the first day of pregnancy resulted in fetal death and resorption. Benz[c ]anthracene has been shown to induce benzo[a]pyrene hydroxylase activity in the rat placenta. 

Person with inherited erythrocyte G6PD deficiency have an enhanced susceptibility to the hemolytic effects of naphthalene, a constituent of the aromatic EC>9-EC16 fraction. Infants appear to be more sensitive than adults to this effect, and infants are more prone to permanent neurological damage as a consequence of the jaundice that results from the hemolysis. Naphthalene has been shown to cross the human placenta to cause hemolysis and hemolytic anemia in the newborn infants of mothers who consumed naphthalene during pregnancy (ATSDR 1995e). 

A variety of effects have been observed in animals treated with toxic doses, but some of these, such as renal damage and anorexia, have not been observed in humans exposed to high doses. The primary tissues of concern in humans are the nervous system and particularly the developing brain, and these have been the main reason for the wide range of epidemiologial studies. Methylmercury passes about ten times more readily through the placenta than other mercury compounds. The dermal absorption of methylmercury is similar to that of inorganic mercury salts. 

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