Hepatic tissue

When ketone bodies are being metabolized in extra-hepatic tissues there is an alternative reaction catalyzed by succinyl-CoA-acetoacetate-CoA transferase (thio-phorase)—involving transfer of CoA from succinyl-CoA to acetoacetate, forming acetoacetyl-CoA (Chapter 22). 

Insulin is secreted as a direct response to hyperglycemia it stimulates the liver to store glucose as glycogen and facilitates uptake of glucose into extra-hepatic tissues. 

Type I Crigler-Najjar syndrome is a rare autosomal recessive disorder. It is characterized by severe congenital jaundice (serum bilirubin usually exceeds 20 mg/dL) due to mutations in the gene encoding bilirubin-UGT activity in hepatic tissues. The disease is often fatal within the first 15 months of life. Children with this condition have been treated with phototherapy, resulting in some reduction in plasma bilirubin levels. Phenobarbital has no effect on the formation of bilirubin glucuronides in patients with type I Crigler-Najjar syndrome. A liver transplant may be curative. 

Garcea, G. et al.. Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration, Br. J. Cancer, 90, 1011, 2004. 

NF-xB activation has been linked with atherosclerosis (Andalibi etal., 1993 Liao etui., 1993). Mice that were maintained on an atherogenic diet, which resulted in ox-LDL accumulation in the liver and arteries, showed NF-xB activation in hepatic tissues. Furthermore, inflammatory gene up-regulation corresponded to the concentration of accumulated lipid peroxides as well as genetic susceptibility to fetty-streak development. 

Fig. 9-4). Very low-density lipoprotein particles are released into the circulation where they acquire apolipoprotein E and apolipoprotein C-II from HDL. Very-low density lipoprotein loses its triglyceride content through the interaction with LPL to form VLDL remnant and IDL. Intermediate-density lipoprotein can be cleared from the circulation by hepatic LDL receptors or further converted to LDL (by further depletion of triglycerides) through the action of hepatic lipases (HL). Approximately 50% of IDL is converted to LDL. Low-density lipoprotein particles are cleared from the circulation primarily by hepatic LDL receptors by interaction with apolipoprotein B-100. They can also be taken up by extra-hepatic tissues or enter the arterial wall, contributing to atherogenesis.4,6... 

Wilson s disease is another autosomal recessive disease leading to cirrhosis. Protein abnormalities result in excessive copper deposition in body tissues. The faulty protein is responsible for facilitating copper excretion in the bile, so copper accumulates in hepatic tissue. High copper levels within hepatocytes are toxic, and fibrosis and cirrhosis may develop in untreated patients. Those with Wilson s disease usually present with symptoms of liver or neurologic disease while still in their teens. 

Prolonged residence in the intestine or urinary bladder lumen could allow time for significant reaction with tissue components however, N-glucuronyloxy-AAF was only weakly carcinogenic at local subcutaneous sites of application (89). Enzymatic deacetylation to N-glucuronyloxy-AF has been detected in hepatic tissue but this activity in different species does not correlate with their relative susceptibility to AAF hepatocarcinogenesis (94). On the other hand, the alkaline pH-induced conversion to a reactive derivative may play an important role in urinary bladder carcinogenesis (87) by AAF and other arylamides in those species or individuals where normal urine pH is alkaline (e.g. normal rabbit urine pH is 8.5-9.0). 

Venugopal, N.B.R.K. and S.L.N. Reddy. 1992a. Effect of bivalent and hexavalent chromium on renal and hepatic tissue glycogen metabolism of a fresh water teleost Anabas scandens. Environ, Monitor. Assess. 21 133-140. 

Mueller and Miller (33) and Brodie et al. (34) were the first to show that enzymes in the microsomal fraction of rat liver could effectively oxidize xenobiotics. Comparable enzymes (aryl hydrocarbon monooxygenases) were later reported in the hepatic tissues of fresh water and marine fish by Creaven et al. (35) and Buhler and Rasmusson (36). Reconstituted hepatic microsomal systems require cytochrome P-450 for monooxygenase activity in both mammals (37) and fish (38,39). Bend et al. 

Information regarding the distribution of the very commonly used detergent sodium lauryl sulfate (SLS) also appears in Table V. Twenty-four hrs. after injection of the form of SLS, most of it (65%) has been excreted in the urine of the shark. At the earlier time point, 4 hrs., the hepatic tissue has a higher concentration and quantity of the detergent than any other tissue. Muscle retained the isotope longer than did other tissues in this table and may represent sulfur exchange with endogenous substances. 

The observed mutagenic responses to AFB reflect the overall effects of activation and detoxification systems on the in vitro metabolism of AFB. It appeared that the effect of high casein levels fed to trout was that a greater amount of activated AFB was produced and/or that less could be detoxified by these fish than by those fed lower casein diets. If lowered cytochrome P-450 content and AE activities in fish fed the high casein diets represented a decrease in the activation of AFB, then these effects were overcome by the observed decreases in GTr activity and/or increases in AFB conversion to AFL relative to those of trout fed lower casein diets. Alternately, the results could be explained by dietary effects upon some unknown OAFB metabolizing enzyme system in trout, upon free GSH levels in hepatic tissue, or that the levels of the cytochrome P-450 involved in AFB activation were not reflected by the observed total cytochrome P-450 levels. 

Chen H, Fantel AG, Juchau MR. 2000. Catalysis of the 4-hydroxylation of retinoic acids by CYP3A7 in human fetal hepatic tissues. Drug Metab Dispos 28 1051-1057. 

Classically the liver has been divided into hexagonal lobules centred around the terminal hepatic venules. Blood enters the liver through the portal tracts that are situated at the corners of the hexagon. The portal tracts are triads of a portal vein, an hepatic artery, and a common hepatic bile duct. The vast expanse of hepatic tissue, mostly consisting of parenchymal cells (PC) or hepatocytes, is serviced via terminal branches of the portal vein and hepatic artery, which enters the tissue at intervals. The hepatocytes are organized into cords of cells radially disposed about the central hepatic venule. Between these cords are vascular sinusoids that transport the blood to the central hepatic venules. The blood is collected through the hepatic venules into the hepatic vein which exits the liver into the inferior vena cava (Figure 4.1). 

In an acute-duration study using pregnant Alderley-Park rats, whole-body exposure to 1,4-diehlorobenzene at air eoneentrations of 74.7, 198.6, or 508.4 ppm, 6 hours a day from Gd 6 to 15 produeed no adverse clinieal or pathologieal signs in the hepatic tissues of the dams (Hodge et al. 1977). In a similar study. New Zealand White rabbits exposed whole-body to 1,4-dichlorobenzene 6 hours a day on Gd 6-18 experieneed no adverse effects on absolute or relative maternal liver weights at air eoneentrations up to 800 ppm (Hayes et al. 1985). 

CYP2A6 is responsible for the majority of coumarin 7-hydroxylase and nicotine C-oxidase activity in hepatic tissue. Substrate selectivity of 2A6 and 2A5 (mouse enzyme) was studied using 23 lactone-containing compounds... 

This is the most highly expressed member of the CYP2C subfamily in hepatic tissues. It is a polymorphic enzyme, and is involved in the metabolism of a number of anti-inflammatory drugs. 

Beside this dermatoxic activity pederin (147) has various biological activities (92). When administered in appropriate doses to partially hepatectomized rats, this compound stimulates development of hepatic tissues. The inhibitory effect at the cellular level has been found in chicken heart fibroblast cultures, and mice embryo, dog kidney, HeLa, and KB cell lines. In plants, root growth of Lupinus albus is inhibited and mitosis in Allium cepa blocked at the metaphasic stage. Also, pederin (147) inhibits protein synthesis and growth of yeast cells. In addition, the treatment of rat ascites sarcoma with purified extracts of P. fuscipes produces almost complete regression. 

While the detection of adducts (GSH, amino, and/or cyano) and covalent binding to hepatic tissue is indicative of the formation of reactive metabolites, the data need to be placed in proper context prior to making a decision on discarding a drug candidate... 

Hatch GE, Santrock J, Slade R, et al. 1988. Detection of CCK induced oxidation of hepatic tissue in vivo by oxygen-18 tracing. Toxicol AppI Pharmacol 93 81-88. 

In the body retinol can also be made from the vitamin precursor carotene. Vegetables like carrots, broccoli, spinach and sweet potatoes are rich sources of carotene. Conversion to retinol can take place in the intestine after which retinyl esters are formed by esterifying retinol to long chain fats. These are then absorbed into chylomicrons. Some of the absorbed vitamin A is transported by chylomicrons to extra-hepatic tissues but most goes to the liver where the vitamin is stored as retinyl palmitate in stellate cells. Vitamin A is released from the liver coupled to the retinol-binding protein in plasma. 

In the oral cavity, drug metabolism occurs in mucosal epithelial cells, microorganisms, and enzymes in the saliva metabolism also takes place in renal and hepatic tissue once the drug is swallowed. Although biotransformation of agents in the oral cavity is potentially an important aspect of reducing effective drug concentra-... 

Hepatoblastoma. A malignant intra-hepatic tumor occurring in infants and young children and consisting chiefly of embryonic hepatic tissue. 

---