Liver Ultrastructure

Strmac, M. and Braunbeck, T. (1999). Effects of triphenyltin acetate on survival, hatching success, and liver ultrastructure of early life stages of zebrafish (Danio rerio). Ecotoxicology and Environmental 44, 25-39. 

Rydzinski, K., Korsak, Z., JedlinSca, U. Sokal, J.A. (1992) The toxic effects of combined exposure to toluene and m-xylene in animals. IV. Liver ultrastructure after subchronic inhalatory exposure. Pol. J. occup. Med. environ. Health, 5, 35-42... 

Larsson-Cohn U, Stenram U. Liver ultrastructure and function in icteric and non-icteric women using oral contraceptive agents. Acta Med Scand 1967 181(3) 257-64. 

Braunbeck, T., V. Storch, and H. Bresch. 1990a. Species-specific reaction of liver ultrastructure in zebra fish (Brachydanio rerio) and trout (Salmo gairdneri) after prolonged exposure to 4-chloroaniline. Arch. Environ. Contam. Toxicol. 19 405-418. 

Partin JS, Daugherty CC, McAdams AJ, Partin JC, Schubert WK (1984) A comparison of liver ultrastructure in salicylate intoxication and Reye s syndrome. Hepatology 4 687-690 Pastorino JG, Simbula G, Yamamoto K, Glascott PA Jr, Rothman RJ, Farber JL (1996) The cytotoxicity of tumor necrosis factor depends on induction of the mitochondrial permeability transition. J Biol Chem 271 29792-29798... 

The cellular/molecular mechanism of action for these cyclic peptide toxins is now an area of active research in several laboratories. These peptides cause striking ultrastructural changes in isolated hepatocytes (95) including a decrease in the polymerization of actin. This effect on the cells cytoskeletal system continues to be investigated and recent work indirectly supports the idea that these toxins interact with the cells cytoskeletal system (86,96). Why there is a specificity of these toxins for liver cells is not clear although it has been suggested that the bile uptake system may be at least partly responsible for penetration of the toxin into the cell (92). 

Elcombe CR, Rose MS, Pratt IS. 1985. Biochemical, histological, and ultrastructural changes in rat and mouse liver following the administration of trichloroethylene Possible relevance to species differences in hepatocarcinogenicity. Toxicol Appl Pharmacol 79 365-376. 

Lemaire, P., J. Berhaut, S. Lemaire-Gony, and M. Lafaurie. 1992a. Ultrastructural changes induced by benzo[a]pyrene in sea bass (Dicentrarchus labrax) liver and intestine importance of the intoxication route. Environ. Res. 57 59-72. 

Anonymous. 1970. Oral toxicity of mirex in adult and suckling rats, with notes on the ultrastructure of liver changes. Arch Environ Health 21 (1 ) 7-14. 

Schecter A, Schaffner F, Tiernan T, et al. 1984. Ultrastructural alterations of liver mitochondria in response to dioxins, furans, polychlorinated biphenyls, and biphenylenes. In Poland A, Kimbrough RD, eds. Biological mechanisms of dioxin action. Cold Spring Harbor, New York Cold Spring Harbor Laboratory, Banbury Report, Vol. 18. Meeting, Cold Spring Harbor, NY, April 1984, 177-190. 

Singh A, Valli VE, Ritter L, et al. 1981. Ultrastructural alterations in the liver of rats fed photomirex (8-monohydromirex). Pathology 13(3) 487-496. 

Because disrupted tissue preparations were unsatisfactory, attempts were made to work either with more organized systems such as tissue slices (liver-Krebs) or to identify and isolate the intracellular organelles involved in the reactions. Cytochemical procedures were developed in the 1930s and 1940s to locate sites of reaction in situ in cells (Chapter 9). Examination of cell ultrastructure became possible when the electron microscope was introduced after 1945. Techniques for the isolation of cell organelles, notably mitochondria, were developed about this time (Chapter 9). 

Terao, K., et al., Histopathological studies on experimental marine toxin poisoning. I. Ultrastructural changes in the small intestine and liver of suckling mice induced by dinophysistoxin-1 and pectenotoxin-1, Toxicon, 24, 11-12, 1141, 1986. 

Dvorak M, Halacka K. 1975. Ultrastructure of liver cells in pig at normal conditions and after administration of small doses of heptachlorine. Folia Morphol 23 71-76. 

Hepatocytes were isolated from male Wistar-derived rats, male Alderley Park guinea-pigs and three human liver samples (liver transplant donors). Treatment with up to 1100 pM metabolite VI for 72 h caused a concentration-dependent induction of cyanide-insensitive palmitoyl-CoA oxidation in rat hepatocytes, but had no significant effect in either guinea-pig or human hepatocytes. Ultrastructural examination revealed an increase in the numbers of peroxisomes in rat hepatocytes, but no such effect was observed in cultured human hepatocytes (Elcombe et al, 1996). 

In mice and rats, di(2-ethylhexyl) adipate induced hepatic markers of peroxisome proliferation (ultrastructural and biochemical) as well as hepatomegaly and increased replicative DNA synthesis. The species differences in carcinogenicity assays of di(2-ethylhexyl) adipate (increased hepatocellular tumours in mice, not rats) are consistent with a higher intake of di(2-ethylhexyl) adipate and a greater extent of peroxisome proliferation and associated responses in livers of mice compared with rats fed the same dietary doses. 

Administration of coumarin to baboons at dose levels of 0, 2.5, 7.5, 22.5 or 67.5 mg/kg bw per day in the diet for 16-24 months resulted in increased relative liver weight only at the highest dose level. While light microscopic examination of liver sections revealed no abnormalities, ultrastructural examination revealed a dilatation of the endoplasmic reticulum in three of four baboons given 67.5 mg/kg per day coumarin (Evans et al, 1979). 

Lee KP, Hebert RR, Sherman H, et al. 1975b. Octabromobiphenyl-induced ultrastructural changes in rat liver. Arch Environ Health 30 465-471. 

Raber BT. Carter JW. 1986. Localization of ultrastructural alterations induced in rat liver by dietary polybromobiphenyls (Firemaster BP-6). Arch Environ Contam Toxicol 15 725-732. 

FIGURE 1.1. Electron micrographs of liver tissue processed differently for transmission electron microscopy. (A) Processed by the conventional method. Note superior quality of ultrastructural preservation compared with that obtained with microwave heating. (B) Rapidly processed by vacuum microwave heating. The whole process from tissue fixation to resin embedding was completed in 2 hr. The quality of ultrastructural preservation is satisfactory. Magnification 6,21 Ox (B). (B) courtesy of Richard T. Giberson. 

Fiejka M, Fiejka E, Dlugaszek M. 1996. Effect of aluminum hydroxide administration on normal mice Tissue distribution and ultrastructural localization of aluminum in liver. Pharmacol Toxicol 78 123-128. 

The primary mechanisms of action in the liver are an impairment of protein synthesis (particularly a decrease in apolipoprotein), resulting in an accumulation of triglycerides, which eventually leads to fibrosis and cirrhosis, and mitochondrial damage, which results in diminished ATP levels, and cell necrosis. Similar mechanisms of action probably occur in the kidney, heart, and brain. A compound that would interfere with the white phosphorus-induced ultrastructural damage would mitigate these effects no compound has been identified that would interfere with this mechanism of action. 

Schecter A, Tieman T, Schaffher F. 1985b. Patient fat biopsies for chemical analysis and liver biopsies for ultrastructural characterization after exposure to polychlorinated dioxins, furans and PCBs. Environ Health Perspect 60 241-254. 

Staubli W, Hess R. 1975. Lipoprotein formation mthe liver cell. Ultrastructural and functional aspects relevant to hypolipidemic action. In Kritchersky D, ed. Handbook of experimental pathology, VoL 41. Hypolipidemic/agents. Berlin Springer-Verlag, 229-289. 

Ham M. and Kaunitz J.D. (2007) Gastroduodenal defense. Curr Opin Gastroentrol 23, 607-616 Hidaka E., Ota H. and Hidaka H. (2001) Helicobacter pylori and two ultrastructurally distinct layers of gastric mucous cell mucins in the surface mucous gel layer. Gut 49, 474-480 Hong D.H., Forstner J. and Forstner G. (1997) Protein kinase C-e is the likely mediator of mucin exocytosis in human colonic cell lines. Am J Physiol Gastrointest Liver Physiol 272,G31-G37... 

In another in vitro study, the effect of uncoupling by DNOC on the structure of rat liver mitochondria was investigated using electron microscopy (Muscatello et al. 1975). When the mitochondria were placed in the uncoupled state, the rate of oxygen uptake was increased and the mitochondria appeared condensed with deep invaginations of the inner membrane, compared to its expanded configuration when DNOC was not present. The authors also determined that the ultrastructural modification was as rapid as the functional one. 

Braunbeck T, Volkl A. 1991. Induction of biotransformation in the liver of Eel (Anguilla anguilla L.) by sublethal exposure to dinitro-o-cresol an ultrastructural and biochemical study. Ecotoxicol Environ Safety 21 (2) 109-127. 

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