Liver foetal

Radulovic LL, Kulkami AP, Dauterman WC. 1987. Biotransformation of methyl parathion by human foetal liver glutathione S-transferases An in vitro study. Xenobiotic 17 105-114. 

AFP is a 70 kDa glycoprotein found in the circulatory system of the developing foetus. It is synthesized primarily by the yolk sac and (foetal) liver. AFP is present only in vanishing low quantities in the serum of adults (where it is replaced by serum albumin). Elevated adult serum levels of this marker are often associated with various cancers of the liver, as well as germ cell tumours. It is also sometimes expressed by gastric and pancreatic cancer cells. Although a useful tumour marker, increased serum AFP levels also often accompany cirrhosis and some other non-cancerous liver diseases. 

Some oxidative (Phase I) drug-metabolizing enzymes are already present in the human foetal liver as early as 12 weeks after conception. Others progressively appear as foetal age advances, although... 

The analgesic paracetamol is largely excreted in the urine of adults as the glucuronide, only around 30% appearing as the sulphate. When human foetal liver cells were incubated with paracetamol, however, they produced the sulphate conjugate but no glucuronide. 

Cole, R.J., Cole, J., Henderson, L., Taylor, N.A., Arlett, C.F. Regan, T. (1983) Short-term tests for transplacentally active carcinogens. A comparison of sister-chromatid exchange and the mieronueleus test in mouse foetal liver erythroblasts. Mutat. Res., 113, 61-75... 

Foetal and neonatal livers contain exceptionally high levels of copper compared to the adult organ. Thus, the livers of new-born rats contain as much as 20 times the level of copper and zinc metallothionein as that found in 70-day-old rats.1150 Again, a metallothionein from foetal bovine liver contained eight copper and two zinc atoms per molecule of protein.1151 These proteins can only be isolated with difficulty under oxygen-free conditions. It appears then that large amounts of copper (and zinc) are stored in the liver bound to metallothionein, and are mobilized as required for enzyme synthesis after birth. 

DMF harmful by inhalation, ingestion or skin contact, may act as a carcinogen, ingestion or absorption through skin may be fatal, exposure may result in foetal death, Long-term exposure may result in kidney or liver damage, irritant... 

Tetrahydrocannabinol is metabolized in the liver to form active metabolites which are further metabolized to inactive polar compounds these are excreted in the urine. Some metabolites are excreted into the bile and then recycled via the enterohepatic circulation. Because of their high lipophilicity, most active metabolites are widely distributed in fat deposits and the brain, from which sources they are only slowly eliminated. The half-life of elimination for many of the active metabolites has been calculated to be approximately 30 hours. Accordingly, accumulation occurs with regular, chronic dosing. Traces of the cannabinoids can be detected in the blood and urine of users for many days after the last administration. There is some evidence of metabolic tolerance occurring after chronic use of the drug. THC and related cannabinoids readily penetrate the placental barrier and may possibly detrimentally affect foetal development. 

D9. Dutton, G. J., Glucuronide synthesis in foetal liver and kidney. Lancet i, 49 (1958). 

Cresteil T, Beaune P, Kremers P, Flinois JP, Leroux JP (1982) Drug-metabolizing enzymes in human foetal liver Partial resolution of multiple cytochrome P450. Paediatr Pharmacol, 2 199-207. 

Factors such as multiplication stimulatory activity (MSA) are produced by foetal rat liver explants and can be obtained from conditioned medium as follows (Nissley et al., 1979) ... 

It is only the ability of modern chemistry to detect very small quantities of materials that made the following discovery possible. In some recent research it was reported that one subtle way in which cancer tumours cells differ from normal cells is how they metabolize carbohydrates present on their surfaces. Cancer cells have far more of the carbohydrate sialic acid, which can be detected with MRI (magnetic resonance imaging) analytical techniques. It was found that the sialic acid normally appears on the surface of the cells only in foetal development, but it appears abnormally in patients with gastric, colon, pancreatic, liver, lung, prostate and breast cancers, as well as in leukaemia. Research is continuing.1... 

It is known that the first aldehyde metabolite of alcohol, acetaldehyde, stimulates collagen transcription in vitro in hepatic fibroblasts and lipocytes [85,86], suggesting a link with alcoholic liver fibrosis in vivo. Chojkier et al. [84] have shown that the lipid-peroxidation product malondialdehyde also increases collagen production 2-3-fold in cultured foetal fibroblasts. The way in which... 

Plant products have also been detected in non-plant organisms. Morphine 1, the archetypal plant alkaloid, has in fact been shown to be a physiological plasma constituent and its production in mammals could be traced to the liver expression of the critical enzymes of its biosynthesis.17 In addition, the plant hormone abscisic acid 12 has been detected as an endogenous constituent of human brain,18 while caffeine 13 was isolated from a marine gorgonian (Paramuricea chamaelon)19 and the atisane diterpenoid serofendic acid 14, an inhibitor of the oxidant-induced mitochondrial death pathway and putative activator of mitoK(ATP) channels, has been characterised from foetal calf serum.20... 

The liver grows quickly, accounting for 10% of foetal mass by the 10th week. This is largely due to the number of newly formed sinusoids, but another important factor is the haematopoietic function of the... 

Expression in foetal liver with activity towards endogenous compounds, e.g. CYP3A7 [15, 16], sulphotransferase [17]. In the case of CYP3A7 expression declines rapidly after birth, to be replaced by CYP3A4/5. Sulphotransferase activity continues. 

Expression in the early neonatal period within hours after birth but with minimal expression in the foetal liver, e.g. CYP2D6 [18], CYP2E1 [19] and glucuronidation [20]. 

GC-MS has been similarly used to give a fuller understanding of in vivo foetal steroid metabolism by studying directly the endogenous content of the adrenals [228,229], testes [230], liver [228,229] and lung [231] in addition to body fluids [232,233] in early and mid-term foetuses. 

Stem cells are progenitor cells which are not yet specifically formed. They can multiply almost infinitely and form nearly all 210 tissue types in the human being. Depending on their derivation, they are defined as follows .) embryonal (= taken from the inner cell mass of the blastocysts), (2.) foetal (= isolated from 5-9 week-old abortive foetuses, and (5.) adult (= taken from the tissue of adults or children by means of biopsy or from the umbilical cord of newborns. Adult stem cells are limited in number and life span they do, however, have a broader development potential than so far assumed. They have also been found in the liver. The transformation of stem cells from the bone marrow into hepatocytes has been carried out successfully. Liver stem cells (7-15 gm) can develop both primary cell types of the liver, (7.) mature hepatocytes and (2.) biliary epithelial cells. These stem cells are deemed to be genuine liver stem cells, and not merely derived from the activation of immature oval cells in the liver. (54,59, 60, 81) (s. fig. 2.20)... 

The oncofoetal antigen Ui-foetoprotein was described in 1963 (G. Abelev et al.) before being detected in 1964 for the first time by Y S. Tatarinov in a patient suffering from liver carcinoma. The glycoprotein AFP is formed in the foetal liver and is biochemically identical to the tumour AFP of hepatocytes. The (physiologically) elevated AFP in the neonate will slowly and steadily decline to reach normal adult levels by the 10 month. 

Monohydroxy bile acids (such as lithocholic acid produced in the intestine) are deemed to be cholestatic factors. They can, however, also be generated in the liver as a result of damage to the smooth endoplasmic reticulmn, with a decrease in activity of cytochrome P 450-dependent 7a-hydroxylase in cases of cholestasis, 3p-hydroxy-5S-cholic add is formed from cholesterol and converted into lithocholic acid and aUo-lithocholic acid (so-called foetal metabolic pathway of bile acids). (10)... 

Among the experimentally tested transplantation sites are the spleen, kidneys, lungs, pancreas, peritoneum, greater omentum and fatty tissue. Up to now, the spleen has proved to be the most suitable. The transplantation of foetal liver cells into the spleen may even culminate in a liver lobule-like formation with bile ducts and veins — however, the functional results have (so far) been no better than with normal hepatocytes. 

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