Liver adaptation

It is noteworthy, here, that one conunercial source of purified alcohol dehydrogenase is horse liver. There is a considerable quantity of this enzyme in horse liver. It is likely that alcohol arises from fermentation in the caecum of the high content of fibre present in the food of the horse. Hence its liver will be exposed chronically to high concentrations of alcohol, and the liver adapts by synthesising large quantities of the enzyme. 

Figure 18.7. Mechanism of biotransformation of bromobenzene in rat liver. [Adapted from...

Lieber, C. S, (1973). Liver adaptation and injury in alcoholism- N. Engl. /. Med. 286,356-362-Licbor, C. S. (198S). Biochemical and inolecuiar basis of alcohol-induced injury to liver and Other tissues. N. Engl. f. Med. 319,1639-1650. 

Fig. 5 Liver-on-a-chip platform. (A) A microfluidic liver on a chip consisting of a liver cell chamber in the center surrounded by a nutrient flow chamber to mimic the structure of the liver (Adapted from [29]). (B) Microengineered perfusion of the hepatic culture (Adapted from [58]). (C) 3D microfluidic liver on a chip consists of two different chambers connected with a tube (Adapted from [57]).

FIGURE 24.13 The subunit structure of medium chain acyl-CoA dehydrogenase from pig liver mitochondria. Note the location of the bound FAD (red). (Adapted from Kim, J-T., and Wiz, J., 1988. Structure of the medium-chain acyl-CoA clchyclro-genase from pig liver mitochonciria at 3-A resolution. Proceedings of the National Academy of Sciences, USA 85 6671-668. )... 

Studies in experimental animals indicate that both toxic effects and adaptive effects may be seen in the liver following oral exposure to endosulfan. 

Table 19-1. Regulatory and adaptive enzymes of the rat (mainly liver).

LFT, liver function tests MIC, minimum inhibitory concentration. Adapted, with permission, from ref. 14. 

Flutamide is an androgen receptor antagonist that achieves peak concentrations approximately 2 to 4 hours after an oral dose. Flutamide is metabolized extensively, with a terminal half-life of about 8 hours. Bicalutamide achieves peak concentrations approximately 6 hours after the dose, with a terminal half-life of 6 to 10 days. Bicalutamide undergoes stereospecihc metabolism, where the S-enantiomer is cleared more rapidly by the liver than the -enantiomer. Nilutamide achieves peak serum concentrations between 1 to 4 hours after an oral dose and has a terminal half-life of 38 to 60 hours. Nilutamide is metabolized extensively, with less than 2% excreted as unchanged drug by the kidney. Side effects common to these agents are hot flashes, gynecomastia, and decreased libido. Flutamide tends to be associated with more diarrhea and requires three-times-daily administration, whereas bicalutamide is dosed once daily. Nilutamide may cause interstitial pneumonia and is associated with the visual disturbance of delayed adaptation to darkness. 

Fate. Preliminary investigations directed at adapting the method of Averell and Norris (2) to the analysis of animal tissues indicated that if precautions were taken to avoid emulsions the method could be used satisfactorily. Tissue samples of about 5 grams were most convenient, and the usual reagent and tissue blanks were run simultaneously. Following the administration of an acutely lethal intravenous dose to a dog it was found that parathion could be recovered from the urine, liver, bile, kidney, spleen, and lung. 

Fig. 8.6 The muscular structure and endocrine glands of man with some specially required elements indicated. (Adapted from Purves et al., Life - the Science of Biology (5th ed.). Associates, Inc. and W.H. Freeman, Sunderland, MA.) Note that organs such as liver are rich in other elements, for example, iron. The large part of the body is linked by internal bones.

Reinheckel T et al. Adaptation of protein carbonyl detection to the requirements of proteome analysis demonstrated for hypoxia/reoxygenation in isolated rat liver mitochondria. Arch Biochem Biophys 2000 376 59-65. 

Fig. 24.1 Variant alleles at the human TPMT locus. Grey boxes are exons containing mutations. White boxes are untranslated regions and black boxes represent exons in the ORF. Dashed box represents exon 2, which was detected in one of 16 human liver cDNAs (adapted from [30]).

Some effects in the liver have been reported, but they may be adaptive changes related to increased metabolic activity. Increased glutathione levels were reported at doses of 70 mg/kg/day for 21 days (Szabo et al. 1977). Because the metabolism of acrylonitrile includes pathways that utilize glutathione (see Section 2.3.3), the higher glutathione levels in the liver may be due to increased demand for glutathione for the metabolism of acrylonitrile. 

A consistent observation in rats exposed to acrylonitrile was increased liver weight, both in acute studies at 65 mg/kg/day (Murray et al. 1978) and chronic studies at 10 mg/kg/day (Bio/dynamics 1980a, 1980b, 1980c). Again, this may be an adaptive change related to increased metabolic activity by the liver due to the presence of acrylonitrile in the body. 

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