Utilization of Electron Probe Microanalysis in Gadolinium-Treated Mice

Wasserman, Arthur J.; Monticello, Thomas M.; Feldman, Robert S.; Gitlitz, Peter H.; Durham, Stephen K.

doi:10.1177/019262339602400508

Cited by 14 publications

(14 citation statements)

References 18 publications

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“…Hepatotoxicity was clearly evident in the present study, although, interestingly, when GdC13 is given at lower dosages the effects on the mononuclear phagocytic system can protect the liver from necrosis induced by some agents (e.g., acetaminophen) (24). At does not make a significant contribution to total plasma ALP in healthy rats, increases in this enzyme have been described in rats given hepatotoxic compounds (7,26).…”

Section: Methodsmentioning

confidence: 43%

“…The ability of intravenously administered GdC'3 to accumulate in Kupffer cells to inhibit their phagocytic ability and lead to their death is well known (15,17,19,24), but effects on the hepatocytes have received little attention (15,22,24). Hepatotoxicity was clearly evident in the present study, although, interestingly, when GdC13 is given at lower dosages the effects on the mononuclear phagocytic system can protect the liver from necrosis induced by some agents (e.g., acetaminophen) (24).…”

Section: Methodsmentioning

confidence: 99%

“…Gadolinium has an anticoagulant effect (9) and Gd salts along with other lanthanide salts have been used to investigate mechanisms of tissue calcification (21,22). Gadolinium salts have also been used in experiments to impair the functioning of the mononuclear phagocytic system and, thus, provide information on the role of Kupffer cells in injury to the liver via a variety of mechanisms (15,17,19,24). In addition, in a pharmacology study in the cat, intravenous Gd chloride (GdCl,) produced hypotension and electrocardiographic abnormalities preceding death (13).…”

Section: Introductionmentioning

confidence: 99%

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Gadolinium Chloride Toxicity in the Rat

et al. 1997

Toxicol Pathol

128

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Groups of 10 male and 10 female Sprague-Dawley rats were given a single intravenous injection of gadolinium chloride solution at dosages of 0 (saline vehicle), 0.07, 0.14, and 0.35 mmol/kg. Apart from 1 top-dose female, which died during dosing, 5 rats/sex/ group were necropsied 48 hr postdose, and the remaining 5 rats/sex/group were necropsied 14 days postdose. Macroscopic, hematological, and clinical chemistry analyses were undertaken on all animals that were necropsied. Histopathological examination was undertaken on all organs from high-dose and control animals necropsied 48 hr postdose and on tissues that showed treatment-related changes from all other rats necropsied either 48 hr or 14 days postdose. Major lesions related to gadolinium chloride administration consisted of mineral deposition in capillary beds (particularly lung and kidney), phagocytosis of mineral by the mononuclear phagocytic system, hepatocellular and splenic necrosis followed by dystrophic mineralization, mineralization of the fundic glandular mucosa in the absence of necrosis followed by mucous cell hyperplasia, decreased platelet numbers and increased prothrombin time, and activated partial thromboplastin time. Electron microscopy and x-ray microanalysis of the spleen and liver revealed electron-dense deposits in splenic macrophages, Kupffer cells, and hepatocytes composed of gadolinium, calcium, and phosphate.

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Section: Methodsmentioning

confidence: 43%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gadolinium Chloride Toxicity in the Rat

et al. 1997

Toxicol Pathol

128

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“…XRMA identified widespread uptake of Gd, calcium, and phosphate complexes in the cells of the mononuclear phagocytic system, notably in the spleen and liver; a nonspecific entrapment of complexes in small blood vessels in the lungs and liver; and dystrophic mineralization in areas of hepatic and splenic necrosis (22). Such a pattern is consistent with the formation of insoluble colloids in the plasma (discussed below) producing an &dquo;embolic shower&dquo; with uptake in splenic macrophages and hepatic Kupffer cells and subsequent necrosis in these organs (16 (26).…”

Section: Ultrastructual Observationsmentioning

confidence: 84%

“…Although some specific effects of Gd salts have been investigated, for instance blockade of the mononuclear phagocytic system, hepatic necrosis, and anticoagulant activity (12,16,22,26), only recently were the effects on all organ systems investigated and reported by our group (22). In that study the effects of a single intravenous administration of gadolinium chloride (GdCl3) in the rat were investigated 2 days and 14 days postadministration over a dosage range from 0.07 to 0.35 mmol/kg (22).…”

Section: Introductionmentioning

confidence: 99%

Time Course of Stomach Mineralization, Plasma, and Urinary Changes After a Single Intravenous Administration of Gadolinium(III) Chloride in the Male Rat

et al. 1997

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Inhibition of Macrophages With Gadolinium Chloride Alters Intercellular Adhesion Molecule–1 Expression in the Liver During Acute Endotoxemia in Rats

et al. 1999

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Cell adhesion molecules are important for localized accumulation of phagocytes at sites of tissue damage. In the present studies, we analyzed the effects of blocking hepatic macrophages on expression of ␤ 2 integrins and intercellular adhesion molecule-1 (ICAM-1) adhesion molecules on liver cells during acute endotoxemia. Flow cytometric analysis revealed distinct subpopulations of macrophages from control animals that varied on the basis of their size and density. In contrast, hepatocytes and endothelial cells were relatively homogeneous. Treatment of rats with endotoxin (5 mg/kg, intravenously) resulted in a time-dependent increase in the percentage of small, dense macrophages and a progressive loss of larger, less-dense cells. In contrast, no major effects were observed on the physical properties of hepatocytes or endothelial cells. ICAM-1 was found to be constitutively expressed on endothelial cells and hepatocytes, as well as on macrophages. Induction of acute endotoxemia resulted in a time-dependent increase in ICAM-1 expression on hepatocytes, which was observed within 3 hours and reached a maximum after 24 hours. An increase in ICAM-1 expression was also observed on endothelial cells and on macrophages at 3 hours, followed by a decrease at 24 to 48 hours. Macrophages and endothelial cells also constitutively expressed ␤ 2 integrins. Induction of acute endotoxemia had no effect on Tissue damage initiates an inflammatory response characterized by an accumulation of macrophages at the site of injury. These cells are primarily derived from blood monocytes. Cell adhesion molecules are a group of membraneassociated proteins present on leukocytes, endothelial cells, and parenchymal cells that facilitate monocyte adherence and emigration out of the blood and into the tissue. Expression of several different classes of cell adhesion molecules have been reported to be up-regulated on liver cells after exposure of animals to hepatotoxic doses of alcohol 1,2 or endotoxin, 3,4 following reperfusion injury, 5,6 and in humans with acute and chronic inflammatory liver diseases. 7-9 Increased quantities of soluble circulating adhesion molecules have also been detected in various models of liver injury. 2,7,8,10 These findings, together with the observation that liver injury is abrogated by administration of antibodies to certain cell adhesion molecules, [4][5][6]11 suggest that they play a role in hepatotoxicity associated with inflammation.Endotoxin is a bacterially derived product known to induce liver injury at toxic doses. 12 We have previously demonstrated that acute endotoxemia is associated with an increase in the number of macrophages in the liver. 13,14 These cells are activated to release reactive oxygen and nitrogen intermediates that we speculate contribute to hepatotoxicity. 14-17 Intercellular adhesion molecule-1 (ICAM-1) is one important cell surface molecule that mediates antigenindependent contact between cells. ICAM-1 serves as a counter-receptor for the ␤ 2 integrins, LFA-1 and MAC-1. [18][19][20] Inter...

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Utilization of Electron Probe Microanalysis in Gadolinium-Treated Mice

Cited by 14 publications

References 18 publications

Gadolinium Chloride Toxicity in the Rat

Gadolinium Chloride Toxicity in the Rat

Time Course of Stomach Mineralization, Plasma, and Urinary Changes After a Single Intravenous Administration of Gadolinium(III) Chloride in the Male Rat

Inhibition of Macrophages With Gadolinium Chloride Alters Intercellular Adhesion Molecule–1 Expression in the Liver During Acute Endotoxemia in Rats

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