Oxidative damage: The biochemical mechanism of cellular injury and necrosis in choline deficiency

Experimental infection of chimpanzees with non-A, non-B hepatitis (NANB) or with delta agent hepatitis results in the appearance of characteristic cytoplasmic alterations in the hepatocytes. These alterations include spongelike inclusions (Type I), attached convoluted membranes (Type II), tubular structures (Type III), and microtubular aggregates (Type IV) (Fig. 1). Type I, II and III structures are, by association, believed to be derived from endoplasmic reticulum and may be morphogenetically related. Type IV structures are generally observed free in the cytoplasm but sometimes in the vicinity of type III structures. It is not known whether these structures are somehow involved in the replication and/or assembly of the putative NANB virus or whether they are simply nonspecific responses to cellular injury. When treated with uranyl acetate, type I, II and III structures stain intensely as if they might contain nucleic acids. If these structures do correspond to intermediates in the replication of a virus, one might expect them to contain DNA or RNA and the present study was undertaken to explore this possibility.

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Erythrophagocytosis in the Liver in Hemolytic Anemias

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100664 ◽

1968 ◽

Vol 26 ◽

pp. 184-185

Author(s):

O. T. Minick ◽

E. Orfei ◽

F. Volini ◽

G. Kent

Keyword(s):

Acid Phosphatase ◽

Oxidative Damage ◽

Phosphatase Activity ◽

Kupffer Cells ◽

Acid Phosphatase Activity ◽

Common Type ◽

Red Cell ◽

Cell Fragments ◽

Reticulo Endothelial System ◽

Important Site

Hemolytic anemias were produced in rats by administering phenylhydrazine or anti-erythrocytic (rooster) serum, the latter having agglutinin and hemolysin titers exceeding 1:1000.Following administration of phenylhydrazine, the erythrocytes undergo oxidative damage and are removed from the circulation by the cells of the reticulo-endothelial system, predominantly by the spleen. With increasing dosage or if animals are splenectomized, the Kupffer cells become an important site of sequestration and are greatly hypertrophied. Whole red cells are the most common type engulfed; they are broken down in digestive vacuoles, as shown by the presence of acid phosphatase activity (Fig. 1). Heinz body material and membranes persist longer than native hemoglobin. With larger doses of phenylhydrazine, erythrocytes undergo intravascular fragmentation, and the particles phagocytized are now mainly red cell fragments of varying sizes (Fig. 2).

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Mitochondrial Changes in Choline-Deficient Rat Myocardium

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100305 ◽

1968 ◽

Vol 26 ◽

pp. 112-113

Author(s):

F. G. Zaki

Keyword(s):

Muscle Fibers ◽

Liver Mitochondria ◽

Ultrastructural Changes ◽

Choline Deficiency ◽

Nutritional Disorder ◽

Low Protein ◽

Structural Abnormalities ◽

Cross Striation ◽

Pericardial Edema ◽

Myocardial Lesions

Choline-deficiency was induced in Holtzman young rats of both sexes by feeding them a high fat - low protein diet.Preliminary studies of the ultrastructural changes in the myocardium of these animals have been recently reported from this laboratory. Myocardial lesions first appeared in the form of intraventricular mural thrombi, loss of cross striation of muscle fibers and focal necrosis of muscle cells associated with interstitial myocarditis. Prolonged choline-deficiency induced cardiomegaly associated with pericardial edema.During the early phase of this nutritional disorder, heart mitochondria - despite of not showing any swelling similar to that usually encountered in liver mitochondria of the same animal - ware the most ubiquitous site of marked structural abnormalities. Early changes in mitochondria appeared as vacuolation, disorganization, disruption and loss of cristae. Degenerating mitochondria were often seen quite enlarged and their matrix was replaced by whorls of myelin figures resembling lysosomal structures especially where muscle fibers were undergoing necrosis. In some areas, mitochondria appeared to be unusually clumped together where some contained membranelined vacuoles and others enclosed dense bodies and granular inclusions.

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Potentiation of bromotrichloromethane hepatotoxicity in male rats exposed to 10 ppm dietary chlordecone: Electron Microscopic and biochemical study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100158972 ◽

1990 ◽

Vol 48 (3) ◽

pp. 284-285

Author(s):

O. M. Faroon ◽

R. W. Henry ◽

M. G. Soni ◽

H. M. Mehendale

Keyword(s):

Free Radical ◽

Biochemical Study ◽

Prior Exposure ◽

Male Rats ◽

Cellular Injury ◽

Low Doses ◽

Mixed Function Oxidase ◽

Electron Microscopic ◽

Potent Inducer ◽

Cellular Energy

Previous work has shown that mirex undergoes photolytic dechlorination to chlordecone (CD) (KeponeR) in the environment. Much work has shown that prior exposure to nontoxic levels of CD causes potentiation of hepatotoxicity and lethality of CCl4, BrCCl3 and other halomethane compounds. Potentiation of bromotrichloromethane hepatotoxicity has been associated with compounds that stimulate the activity of hepatic mixed-function oxidase (MFO). An increase in the metabolism of halomethane by the MFO to a free radical initiates peroxidative decomposition of membranal lipids ending in massive cellular injury. However, not all MFO inducers potentiate BrCCl3 hepatotoxicity. Potentiation by much larger doses of phenobarbital is minimal and th at by a more potent inducer of MFO, mirex, is negligible at low doses. We suggest that the CD and bromotrichloromethane interaction results in a depletion of cellular energy and thereby reducing the cellular ability to undergo mitosis.

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