Hver cells

Hepatocytes are the dominant cell type in the Hver constituting approx. 70% of all hver cells. They are responsible for the uptake of substances from the blood and for the excretion by the bihary system. Specific requirements have to be met by compounds to be able to enter the hepatocytes. These are definite ranges of molecular weight, lipophiHcity and polarity or charge. Additionally, receptor-mediated transport systems of the hepatocytes pose further requirements on the structure of the substance. 

Because of the need for isolation techniques applicable to other species, Hoogenboom et al [18] investigated the isolation of hepatocytes from porcine livers and developed an enzymatic method with closed-loop and open-loop perfusion stages for the perfusion of liver lobes. We investigated a method to perfuse the whole organ to receive a great amount of hver cells (up to 25-10 cells per pig liver) and a viability higher than 90%. 

Lindahl-Kiessling, K., Karlberg, 1. Olofsson, A.-M. (1989) Induction of sister-chromatid exchanges by direct and indirect mutagens in human lymphocytes, co-cultured with intact rat liver cells. Effect of enzyme induction and preservation of the hver cells by freezing in liquid lutrogen. Mutat. Res., 211,11-Kl... 

Kamps, J.A., Morselt, H.W., and Scherphof, G.L., 1999, Uptake of liposomes containing phosphatidylserine by hver cells in vivo and by sinusoidal hver cells in primary culture in vivo - in vitro differences, Biochem. Biophys. Res. Commun. 256 57-62. 

While in vitro experiments offer a partial solution to the safety evaluation of chemicals, they cannot completely replace animal experiments for this purpose. Many chemicals are poisonous because they affect organs or systems as well as, or rather than, individual cells. The human body, like that of any mammal, is a highly complex, integrated system and reacts to chemicals in many different ways, far more than can be predicted from one or two different types of isolated cells. Most of the cells in our bodies have some similarities (for example, they all have a nucleus), but brain cells are very different from muscle cells, otherwise we would not be able to think Different types of cells have specialized functions which can make them a target for chemicals in specific ways. In particular, their metabolic capabihties are different and they may be unable to detoxify chemicals in the same way as hver cells, for example. This is illustrated by the story on p. 296. There is no doubt that the world would be a more hazardous place if the safety of chemicals were evaluated only in vitro. 

Levine L. Statins stimulate arachidonic acid release and prostaglandin 12 production in rat hver cells. Lipids Health Dis. 2003 2 1. 

Fig. 2.13 Diagram of the classic hepatic lobule (I), the portal vein lobule (II) and the hepatic acinus (III) CV = central vein ( ), P = portal tract ( ). Flow direction venous blood (= blue arrow), arterial blood (= red arrow) and bile (= green arrow), with the microcirculatory acinus zones 1, 2, 3. (cf. W Ekataksin et af, 1992 the microvascular unit is regarded as an area in which all hver cells receive blood from a common terminal vessel)...

H.D. Angiographic findings in benign hver cell tumors. Radiology 1974 110 339 - 343... 

Reduced storage of bilirubin can be caused by the bilirubin competing with exogenous substances for binding to the Y protein or with long-chain fatty adds for binding to the Z protdn. Thus bilirubin may diffuse back from the hver cell into the blood. 

BLSS The bioartificial hver support system is made up of a blood pump, a heat exchanger to control the blood temperature, as well as an oxygenator and a bioreactor. The hollow-fibre bioreactor generally contains 70—100 g of porcine hver cells. Initial experience with BLSS is encouraging. (92)... 

In histomorphological terms, hepatitis means inflammation of the liver . The factor causing the disease may spread from the initially or predominantly affected mesenchyma to the liver cells (such as in kala-azar and malaria), or the primarily or mainly affected Hver cells may subsequently incorporate the mesen-ch)mia into the damaging process (as for example in yellow fever). In leptospirosis and herpes virus infection, the morphological finding is determined almost exclusively by changes in the parenchyma, while mesench)mial reactions are hardly or not at all present. 

An increase in uric add values up to an acute gout attack can only be attributed to a minor extent to diminished uric acid excretion from the kidneys, since decreased uricosuria due to hyprerlactacid-aemia is generally not observed unless the lactate value is >2 mmol. Excessive production of uric acid caused by increased catabolism of preformed purine nucleotides is considered to be an essential cause. This is also supported by the observation that the purine nucleotide content in hver cells is diminished after prolonged alcohol consumption. (36) (s. tab. 28.2)... 

Terbinafine can cause hepatitis, with an estimated rate of about 1 in 50 000 (34). Idiosyncratic reactions can lead to hver cell necrosis as well as cholestasis. Prolonged cholestatic hepatitis and liver failure have been reported (35-39). 

Renal tubular cells are able to generate ammonia from glutamine and other amino acids derived from muscle and hver cells according to the following reaction ... 

B. N. Melgert, K. Poelstra, V. K. Jack, G. Molema, and D. K. F. Meijer, Dexameth-asone coupled to albumin is taken up by non parenchymal hver cells and protects against endotoxin in rats with hver cirrhosis. Hepatology 2S 440A [abstract] (1998). 

M5. Marquardt, H., Todaro, G. J., Henderson, L. E., and Oroszlan, S., Purification and primary structure of a polypeptide with multiplicating-stimulating activity from rat hver cell cultures.. Biol. Chem. 256, 6859-6865 (1981). 

Fatty Liven The buildup of fat in hver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [NIH]... 

Approximately half of the VLDL remnants are not taken up by the liver but, instead, have additional core triacylglycerols removed to form IDL, a specialized class of VLDL remnants. With the removal of additional triacylglycerols from IDL through the action of hepatic triglyceride lipase within hepatic sinusoids, LDL is generated from IDL. As seen in Table 34.4, the LDL particles are rich in cholesterol and cholesterol esters. Approximately 60% of the LDL is transported back to the hver, where its apoB-100 binds to specific apoB-100 receptors in the hver cell plasma membranes, allowing particles to be endocytosed into the hepatocyte. The remaining 40% of LDL particles are carried to extrahepatic tissues such as adrenocortical... 

Ann Jeina was treated with a statin (pravastatin) and cholestyramine, a bile acid sequestrant. With the introduction of the cholesterol absorption blocker ezetimibe, the use of cholestyramine with its high level of gastrointestinal side effects may decline. Ezetimibe reduces the percentage of absorption of free cholesterol present in the lumen of the gut and hence the amount of cholesterol available to the enteroc5de to package into chylomicrons. This, in turn, reduces the amount of cholesterol returning to the liver in chylomicron remnants. The net result is a reduction in the cholesterol pool in hepatocytes. The latter induces the synthesis of an increased number of LDL receptors by the hver cells. As a consequence, the capacity of the liver to increase hepatic uptake of LDL from the circulation leads to a decrease in serum LDL levels. 

Chen, J. and G.J. Barritt, Evidence that TRPCl (transient receptor potential canonical 1) forms a Ca -permeable channel linked to the regulation of cell volume in hver cells obtained using small interfering RNA targeted against TRPCl. Biochem J, 2003 373 (Pt 2) 327-336. 

Where within a hver cell does fatty acid synthesis occnr ... 

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