Liver injury in hypervitaminosis A: Evidence for activation of Kupffer cell function.

Persistent Link:
http://hdl.handle.net/10150/184410
Title:
Liver injury in hypervitaminosis A: Evidence for activation of Kupffer cell function.
Author:
Sim, Wai-Lum Winnie.
Issue Date:
1988
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The most important and novel finding of this work was enhanced liver Kupffer cell phagocytic and metabolic function by hypervitaminosis A. An animal model of hypervitaminosis A was developed in male Sprague-Dawley rats gavaged with 250,000 I.U. retinol/Kg body weight/day for 3 weeks. Presence of hypervitaminosis A was indicated by characteristic changes in the fur coat, presence of brittle bones and spontaneous fractures and a significant increase in plasma and liver concentrations of retinyl palmitate while retinol levels remained the same as in controls. Hypervitaminosis A did not cause severe liver abnormalities as reflected by normal plasma glutamate pyruvate transaminase activity and bilirubin. Hepatic blood flow and portal pressure were also normal. Liver microsomal cytochrome P-450 was decreased while malondialdehyde, a by-product of lipid peroxidation, was increased by the Vitamin A treatment. Examination of liver tissue by light microscopy showed no signs of liver cell injury. The main change was a marked increase in size of the fat or Vitamin A storing cells. Although hypervitaminosis A itself did not cause severe liver damage, pretreatment with high doses of Vitamin A severely potentiated liver injury by known hepatotoxicants such as carbon tetrachloride, endotoxin and acetaminophen. The potentiation of hepatotoxicity was determined by activity of glutamate pyruvate transaminase in plasma as well as by histological examination of liver tissue. Measurement of clearance from blood of indocyanine green and ⁹⁹ᵐTc-disofenin indicated this hepatocyte function was normal. Kupffer cell phagocytic function was enhanced in hypervitaminosis A as determined by clearance from blood of ⁹⁹ᵐTc-sulfur colloid. In vitro, there was also evidence that treatment with high doses of Vitamin A activated or enhanced Kupffer cell function. Kupffer cells from control and Vitamin A treated rats were isolated by enzymatic dispersion, purified by centrifugal elutriation, and placed in culture. Activation was indicated by (1) increased phagocytosis of ⁵¹Cr-labeled opsonized sheep red blood cells (2) enhanced release of superoxide anion and (3) enhanced production of tumor cytolytic factor by Kupffer cells from Vitamin A treated rats. Stimulation of Kupffer cell function in hypervitaminosis A seemed to be via lymphokines produced by lymphocytes in response to the excess Vitamin A. We propose that activated Kupffer cells may play an important role in liver injury in hypervitaminosis A.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Hypervitaminosis.; Vitamin A in the body.; Kupffer cells.; Liver -- Diseases.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Nutritional Sciences; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Earnest, David L.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleLiver injury in hypervitaminosis A: Evidence for activation of Kupffer cell function.en_US
dc.creatorSim, Wai-Lum Winnie.en_US
dc.contributor.authorSim, Wai-Lum Winnie.en_US
dc.date.issued1988en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe most important and novel finding of this work was enhanced liver Kupffer cell phagocytic and metabolic function by hypervitaminosis A. An animal model of hypervitaminosis A was developed in male Sprague-Dawley rats gavaged with 250,000 I.U. retinol/Kg body weight/day for 3 weeks. Presence of hypervitaminosis A was indicated by characteristic changes in the fur coat, presence of brittle bones and spontaneous fractures and a significant increase in plasma and liver concentrations of retinyl palmitate while retinol levels remained the same as in controls. Hypervitaminosis A did not cause severe liver abnormalities as reflected by normal plasma glutamate pyruvate transaminase activity and bilirubin. Hepatic blood flow and portal pressure were also normal. Liver microsomal cytochrome P-450 was decreased while malondialdehyde, a by-product of lipid peroxidation, was increased by the Vitamin A treatment. Examination of liver tissue by light microscopy showed no signs of liver cell injury. The main change was a marked increase in size of the fat or Vitamin A storing cells. Although hypervitaminosis A itself did not cause severe liver damage, pretreatment with high doses of Vitamin A severely potentiated liver injury by known hepatotoxicants such as carbon tetrachloride, endotoxin and acetaminophen. The potentiation of hepatotoxicity was determined by activity of glutamate pyruvate transaminase in plasma as well as by histological examination of liver tissue. Measurement of clearance from blood of indocyanine green and ⁹⁹ᵐTc-disofenin indicated this hepatocyte function was normal. Kupffer cell phagocytic function was enhanced in hypervitaminosis A as determined by clearance from blood of ⁹⁹ᵐTc-sulfur colloid. In vitro, there was also evidence that treatment with high doses of Vitamin A activated or enhanced Kupffer cell function. Kupffer cells from control and Vitamin A treated rats were isolated by enzymatic dispersion, purified by centrifugal elutriation, and placed in culture. Activation was indicated by (1) increased phagocytosis of ⁵¹Cr-labeled opsonized sheep red blood cells (2) enhanced release of superoxide anion and (3) enhanced production of tumor cytolytic factor by Kupffer cells from Vitamin A treated rats. Stimulation of Kupffer cell function in hypervitaminosis A seemed to be via lymphokines produced by lymphocytes in response to the excess Vitamin A. We propose that activated Kupffer cells may play an important role in liver injury in hypervitaminosis A.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHypervitaminosis.en_US
dc.subjectVitamin A in the body.en_US
dc.subjectKupffer cells.en_US
dc.subjectLiver -- Diseases.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineNutritional Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorEarnest, David L.en_US
dc.contributor.committeememberSipes, I. Glennen_US
dc.contributor.committeememberChvapil, Milosen_US
dc.contributor.committeememberLei, David K. Y.en_US
dc.contributor.committeememberWatson, Ronald R.en_US
dc.identifier.proquest8814277en_US
dc.identifier.oclc701248428en_US
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