Liver accumulation

Hypolipoproteinemias Abetaiipoproteinemia No chylomicrons, VLDL, or LDL are formed because of defect in the loading of apo B with lipid. Rare blood acylglycerols low intestine and liver accumulate acylglycerols. Intestinal malabsorption. Early death avoidable by administration of large doses of fat-soluble vitamins, particularly vitamin E. 

Liver sends triglycerides to adipose tissue packaged as very low-density lipoproteins (VLDL reviewed later in this chapter). A small amount of triglyceride may be stored in the liver. Accumulation of significant triglyceride in tissues other than adipose tissue usually indicates a pathologic state. 

Labbe, G. et al. (1991) Effects of various tetracycline derivatives on in vitro and in vivo beta-oxidation of fatty acids, egress of triglycerides from the liver, accumulation of hepatic triglycerides, and mortality in mice. Biochemical Pharmacology, 41 (4), 638-641. 

The minimum antibody binding domain, Fv, has also been linked to toxin to produce a more compact, recombinant immuno-toxin. The recombinant F -toxin appears to be more stable and exhibits less liver accumulation [27,28]. The immunogenicity of Fv-toxin as a consequence of the highly antigenic determinants of bacterial toxin remains a barrier to development. 

E. coZZ-infected chickens, residues could be detected in tissues of both healthy and infected birds (184). Residual levels in infected birds were higher than those of healthy birds and remained longer in bile for 4 days after multiple administration. Bile, kidney, and liver accumulated the highest concentration of the drug. 

Ethionine is a hepatotoxic analogue of methionine causing fatty liver (accumulation of triglycerides). Chronic exposure causes cirrhosis, bile duct proliferation, and heptatocellular carcinoma. It forms S-adenosyl ethionine, which traps adenosyl leading to ATP depletion, which reduces triglyceride export from the liver. It also leads to ethylated bases in DNA. 

Intermediate-duration exposure to 2,3,7,8-TCDD in the feed has been shown to produce higher liver accumulation in male (85%) than in female rats (70%) (Fries and Marrow 1975). The percentage retained was related to intake, and at steady state, the total amount retained was about 10.5 times the average daily intake. 

P Sinclair Department of Veterans Affairs Medical Center, White River Junction, VT Determine the mechanism by which 2,3,7,8-TCDD and related planar PAHs cause massive liver accumulation of uroporphyrin (URO) ... 

The chromium content in major organs of mice receiving drinking water that provided doses of 4.8, 6.1, or 12.3 mg chromium(III)/kg/day as chromium trichloride or 4.4, 5.0, or 14.2 mg chromium(VI)/kg/day as potassium dichromate was determined after 1 year of exposure. Chromium was detected only in the liver in the chromium(III)-treated mice. Mice treated with chromium(VI) compounds had accumulation in all organs, with the highest levels reported in liver and spleen. Liver accumulation of chromium was... 

The bile acids produced by the liver accumulate in the gall bladder in the form of bile salts they are bile acids in which the carboxylic acid group is conjugated with glycine or taurine. 

Liver. In humans, chronic Cd exposure does not typically result in hepatotoxicity. In laboratory animals, the liver accumulates the largest concentrations of Cd after acute or chronic exposures. In chronically exposed rats, liver injury occurs prior to renal dysfunction. Chronic Cd effects in the liver include increased plasma activities of alanine and aspartate aminotransferases, structural irregularities in hepatocytes, and decreased microsomal mixed function oxidase and CYP450 activities. Acute exposures in rats result in hepatic necrosis, particularly in parenchymal cells. Additionally, rough endoplasmic reticulum deteriorates, while smooth endoplasmic reticulum proliferates. Mitochondria are also degraded. As is the case with chronic exposure, microsomal mixed function oxidases and CYP450s are inhibited. 

Glycogen synthase Enlarged liver, accumulation of fat (fatty liver) fasting hypoglycaemia occasional muscle cramping... 

In analysis of the hver metabolism in rats treated with anti-colorectal carcinoma mAh 1A3 radiolabeled with Cu through three different macrocyclic bifunctional chelates, it was apparent that the radiocopper was transchelated and bound to proteins such as superoxide dismutase (SOD see Copper Proteins with Type Sites). Transchelation of the copper radiolabel appears to be a major factor for liver accumulation ofthe Cu-labeledBFC-lA3 conjugates After extensive evaluation, experimental results are consistent with in vivo transchelation of Cu from TETA-octreotide to superoxide dismutase (SOD) in rat liver. ... 

Figure 20. C-NMR spectra from a perfused mouse liver at SS C. (c) C natural abundance background of this liver, accumulated before the substrate was added. The substrate, 8 mM [3- C]alanine and 20 mM unlabelled ethanol, was then added at 0 minutes and again at 120 minutes, and a series of C-NMR spectra were taken, (b) Spectrum measured during the period 150-180 minutes (a) C-NMR spectrum of the perfusate after the perfusion was terminated, at 240 minutes this spectrum consisted of 5000 scans. The pulse repetition times were 0.5 seconds for b and c and 2 seconds for a. Abbreviations pci, oCl, ]9C3.5, aC4, pC6, aC6, PC2, C2.5 and aC3, the carbons of the glucose anomers Glu C2, glutamate C-2 Gin C2, glutamine C-2 Asp C2, aspartate C-2 Ala C2, alanine C-2 LacC3, lactate C-3 CB, cell background peak W, X, Y and Z, unknowns AA Ca, acetoacetate CHj and / -HB Ca, -hydroxybutyrate CHj (from [31]).

However, every molecule of acetoacetic add or its derivatives that the liver accumulates and subsequently excretes means that two potential acetyl-CoA molecules have not been exploited so as to release their potential energy through oxidation by way of the citric add cycle. Why Particularly as fatty acid oxidation only occurs under conditions of carbohydrate starvation, one may well... 

Fig. 5.1 Whole-body images of a patient with non-Hodgkin s lymphoma at selected times after administration of In-labeled ibritumomab tiuxetan (Zevalin ) demonstrating strong uptake of radioactivity in regions of periaortic lymphadenopathy (red arrows). Normal liver accumulation ofZeva-lin is also observed. [Reprinted from Witzig T. E., et al.J. Clin. Oncol. 1999 3793-3803.]...

Similar findings in terms of liver accumulation were found in a study in which two female LAC Porton rats were fed 10 mg/kg of 14C-MBOCA, and MBOCA s distribution was measured 48 hours later (Farmer et al. 1981). Again, liver had the highest amount of radioactivity, followed by white fat, blood, and kidney. This study is limited because it used only two animals. In another acute study, radiolabeled MBOCA was administered by gavage to rats by gavage (Morton et al. 1988). Forty-eight hours later, 64-87% of the administered radioactivity was recovered in the urine and feces. 

One hour after a single intravenous dose of 0.49 mg/kg of radiolabeled MBOCA to rats, radioactivity was found in the tissues in the following order small intestine gt liver > fat tissue > lungs > kidneys > skin > adrenals (Tobes et al. 1983). Similar results in terms of liver accumulation were obtained in rats 48 hours after an intraperitoneal injection of 1 mg/kg of radioactive MBOCA (Farmer et al. 

The most significant biological consequence of nanocarrier modification with protecting polymers is a sharp increase in the carrier circulation time and decrease in its RES (liver) accumulation. ° This fact is very important clinically, since various long-circulating nanocarriers have been shown to effectively accumulate in many tumors via the EPR effect. ... 

Unlike all other species, marmoset monkeys cannot metabolize iAs to methylated forms. During 4 days after i.p. administration of 0.4mg As Vkg, marmoset monkeys eliminated only 30% of the dose, mainly via urine (Vahter et al. 1982). As in urine and tissues of marmosets was iAs. Liver accumulated the largest portion of the dose (20%). Half of the liver As was bound to the rough microsomal membranes. No biotransformation (except of partial reduction of As to As ) was found after i.v. injection of 0.4mg As /kg (Vahter and Marafante 1985). Within 3 days posttreatment, about 39% of the dose was excreted in urine and only 2% in feces. Urinary As consisted of iAs and iAs present at a ratio of 1 1. The basis for the absence of iAs methylation in marmoset monkeys remains unknown. In contrast to the marmoset, other monkey species Cynomologus and Rhesus)... 

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