Placental permeability

Within the OAT family, OAT4 is the only transporter expressed at appreciable levels in both the placenta and in the kidney [54]. The membrane localization of OAT4 within these tissues has not been examined. Steroid sulfates, and ochratoxinA are efficient transport substrates of OAT4, whereas PAH is weakly transported [54]. The functional importance of OAT4 in regulating placental permeability and renal drug elimination is currently unknown. 

Willhite CC, Ferm VH, Zeise L. 1990. Route-dependent pharmacokinetics, distribution, and placental permeability of organic and inorganic selenium in hamsters. Teratology 42(4) 359-371. 

Sundareson AE. An experimental study on placental permeability to cirrhogenic poisons. J Pathol Bacteriol 1942 54 289-98. 

Haelon dp and Perm VH (1977) Placental permeability of arsenate ion during early embryogenesis in the hamster. Experientia 33 1121 — 1122. 

Secretion from the mammary glands of the newborn of both sexes thought to be due to placental permeability to the lactation-producing hormones of the mother. 

Specific barriers may serve to limit dmg distribution. The placental barrier is of obvious importance to dmg action in the fetus. Dmg transfers across the placenta primarily by Hpid solubiHty. Hence, this barrier is not particularly restrictive. Similarly, the Hpid solubiHty of a dmg is a primary deterrninant in access to the brain and cerebrospinal fluid. Generally, hydrophilic or charged dmgs can also penetrate to these latter areas, but the result is slow and incomplete. The blood brain barrier is composed of cells having tight junctions which are much less permeable to solutes than are the endotheHal cells of other tissues. 

Placental tissue incubated for as long as 24 h in media containing 145 mg Ni/L MONKEYS When compared to controls, treated tissues had increased permeability, lipid peroxidation, and nickel concentration over time. Treatment with ascorbic acid or zinc decreased nickel-induced placental lipid peroxidation and permeability, but had no effect on nickel tissue concentrations 43... 

Either Transwell inserts or side-by-side diffusion chambers can be used for transport studies. Bode et al. have provided an excellent review on this subject [60], Briefly, cells are incubated for 30-60 min with a buffer solution. To initiate the transport study, a transport buffer containing the drug under investigation is added to either the apical or the basal chamber depending on the transport direction of interest. At predetermined time points, the respective receiver chamber is sampled and the withdrawn volume is replaced with the same volume of fresh buffer. The permeability coefficient (Papp) is calculated and the ratio of /apP in the basolateral-to-apical direction versus that in the apical-to-basolateral direction gives the efflux ratio. These sort of transport experiments are well suited to determine if drugs/xenobiotics are substrates of the placental efflux proteins. 

They possess a higher permeability to drugs than is suggested by the term placental barrier". 

Nowhere are the effects of the permeability of the placental membrane more graphic than in the incidence of fetal alcohol syndrome (FAS) in the children of alcoholic mothers. FAS produces distinctive anatomical features and mental retardation. Ethanol is called a teratogen because it causes genetic malfunction. Recall that thalidomide was a teratogen. 

The biochemical aspects of teratology are not particularly well understood. Several kinds of biochemical mechanisms are probably involved. One such mechanism is interference with DNA synthesis, which alters the function of nucleic acids in cell replications, resulting in effects that are expressed as birth defects. Exposure to teratogenic xenobiotic substances may result in either an absence or excess of chromosomes. Enzyme inhibition (see Section 7.6) by xenobiotics can result in birth defects. Xenobiotics that deprive the fetus of essential substrates (for example, vitamins), that interfere with energy supply, or that alter the permeability of the placental membrane may all cause birth defects. 

Tissue distribution of phenylmercury is initially similar to methylmercury. One week after administration, the distribution pattern resembles that seen after administration of inorganic compounds (Nordberg 1976). Once in the blood, phenylmercury distributes to a greater extent into the red blood cells than the plasma. Phenylmercury also predominantly distributes to the liver (Berlin 1963). It is less permeable to the placental and blood-brain barriers than methylmercury (Yamaguchi and Nunotani 1974). Phenylmercury also accumulates in the fur of rats but to a lesser extent than detected with methylmercury exposure (Gage 1964). 

Teratogens are chemical species that canse birth defects. These usually arise from damage to embryonic or fetal cells. However, mntations in germ cells (egg or sperm cells) may canse birth defects, snch as Down s syndrome. The biochemical mechanisms of teratogenesis are varied. These include enzyme inhibition by xenobiotics deprivation of the fetus of essential substrates, such as vitamins interference with energy supply or alteration of the permeability of the placental membrane. 

A variety of biochemical effects caused by xenobiotics may be responsible for teratogenesis. These include enzyme inhibition, interference with energy supply, deprivation of the fetus of vitamins and other essential substrates, and altered permeability of the placental membrane. 

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