Liver and Environmental Xenobiotics

243 Pages·1997·15.2 MB·English

by  P. R. Sudhakaran

Liver and Environmental
_____ Xenobiotics
Liver and Environmental
_____ Xenobiotics
Editors
S.V.S. Rana
K. Taketa
Springer-Verlag Berlin Heidelberg GmbH
EDITORS
S.V.S. Rana
Department of Zoology
Ch. Charan Singh University
Meerut 250 004, India
K. Taketa
Department of Public Health
Okayama University Medical School
Okayama 700, Japan
Copyright © 1997 Springer-Verlag Berlin Heidelberg
Originally published by Berlin Heidelberg New York in 1997
All rights reserved. No part of this publication may be reproduced, stored in a retrieval
system. or transmitted in any form or by any means. electronic. mechanical. photocopying.
recording or otherwise. without the prior permission of the publisher.
Exclusive distribution in North America (including Canada and Mexico) and Europe by
Springer-Verlag Berlin Heidelberg GmbH.
All export rights for this book vest exclusively with Narosa Publishing House.
Unauthorised export is a violation of Copyright Law and is subject to legal action.
ISBN 978-3-662-12387-4 ISBN 978-3-662-12385-0 (eBook)
DOI 10.1007/978-3-662-12385-0
_______ Foreword ________
Today the general populations are incidentally exposed to a wide variety of
xenobiotics as a consequence of the pollution of the environment by industrial
and agricultural chemicals. The action of these xenobiotics on the body
shows certain specificity, depending upon the compound's chemical structure
and reactivity. Further, the final exposition of cytotoxicity and genetic
injury is determined by receptors, enzyme active or regulatory sites, structural
elements and ion channels as weB as covalent interactions with tissue
macromolecules including nucleic acids. The consequences of metabolism
for the pharmacological and toxic activity of a compound may involve a
number of possibilities. It may form reactive species and cause oxidative
stress. Free radicals are important in tissue damage, e.g., in intlammation,
ageing and chemical injury so that their formation as a consequence of
xenobiotic metabolism is noteworthy.
Hepatocellular degeneration and death are amongst the most important
effects caused by these xenobiotics. There are well accepted mechanisms
for a few of them. However, we have to update our knowledge on many
others. Therapeutic advances are also to be considered. There have not
been sufficient attempts to study liver protective mechanisms.
I am happy to go through this book that not only describes general
aspects of toxic liver injury but also deals with the involvement of liver in
handling the industrial and environmental xenobiotics.
Dr. S.V.S. Rana studied toxic liver injury in the Department of Public
Health, Okayama University Medical School, Japan as a Senior JSPS scientist
when I worked as Professor and Chairperson. In 1991, Dr. Kazuhisa Taketa
took over as Professor and Chairman of the Department of Public Health.
Dr. Rana worked in that Department again in 1995. They worked together
on this book. In my opinion this colabortion has been successful and I wish
them success in their future endeavours.
MASANA OGATA
MD
Kawasaki University of Medical Welfare
Japan
Preface
The general populations are incidentally exposed to a wide variety of
xenobiotics as a consequence of the pollution of the environment by industrial
and agricultural chemicals. Xenobiotics entering the animal will undergo
one or more of the following fate: (a) elimination unchanged, (b) metabolism
by enzymes, (c) spontaneous chemical transformation and (d) remain
unchanged in the body. The actions of xenobiotics on the body exhibit
certain specificity depending upon the compound's chemical structure and
reactivity. Since the processes of metabolism change these chemical properties
ofaxenobiotic, bewildering number of reactions continue to pose new
challenges to toxicologists and pharmacologists. It necessitates periodic
and precise revision of the subject.
This book contains invited contributions from learned colleagues that
offer an excellent survey of and profound insight into the disposition and
metabolism of a few environmentally and industrially significant xenobiotics.
The topics range from an assessment of drug metabolising enzymes in the
liver, DNA damage by reactive oxygen species generated by pesticides,
role of NO in liver injury, hepatotrophicgrowth factor in liver regeneration,
extracellular matrix in the liver, oncogene expression in liver injury, the
hepatocarcinogenesis to oxidative stress and undifferentiated gene expression.
Detailed analysis of the validity of liver function tests has been included.
Last Chapter addresses the problem of apoptosis, which plays a key role in
the signal transduction system of xenobiotics-induced liver injury.
The reader should appreciate that overall exposure to this field is expanding
at a rapid pace and selections had to be made.
During the development of this book, we received help and advice from
many colleagues for which we are thankful. We gratefully acknowledge the
understanding, care and precision of the publisher that made this book
possible.
EDITORS
Contents
Foreword v
Preface vii
1. Extracellular Matrix in Liver 1
P.R. Sudhakaran, N. Anil Kumar and
Anitha Santhosh
2. Drug Metabolizing Enzymes in the Liver 19
Mohammad Athar, S. Zakir Husain and
Nafisul Hasan
3. Liver Injury: Genetic factors in alcohol and
acetaldehyde metabolism 31
Mikihiro Tsutsumi and Akira Takada
4. An Enhanced Liver Injury Induced by Carbon
Tetrachloride in Acatalasemic Mice 40
Kunihiko Ishii, Da-Hong Wang, Li-Xue Zhen,
Masaki Satho and Kazuhisa Taketa
5. Liver Injury in Ischemia and Reperfusion 53
Koji Ito, lunichi Vchino, Yasuaki Nakajima and
fun Kimura
6. Liver Injury and Serum Hyaluronan 61
Takato Veno and Kyuichi Tanikawa
7. Phthalic Acid Esters and Liver 72
D. Parmar and P.K. Seth
8. Role of Nitric Oxide (NO) in the D-Galactosamine-
Induced Liver Injury 92
Hironori Sakai, Hidehiko Isobe and Hajime Nawata
9. Generation of Reactive Oxygen Species, DNA Damage
and Lipid Peroxidation in Liver by Structurally
Dissimilar Pesticides 102
S.J. Stohs, D. Bagchi, M. Bagchi and E.A. Hassoun
10. Oxidative Stress and Liver Injury by Environmental
Xenobiotics 114
S. V.S. Rana
x Contents
11. Experimental Hepatocarcinogenesis and
Its Prevention 135
Kiwamu Okita, Isao Sakaida and Yuko Matsuzaki
12. Oncogene Expression in Liver Injury 151
Yutaka Sasaki, Norio Hayashi, Masayoshi Horimoto,
Toshifumi Ito, Hideyuki Fusamoto and Takenobu Kamada
13. Undifferentiated Gene Expression as the Entity of
Liver Injuries 167
Kazuhisa Taketa
14. Standard Liver Function Tests and Their
Limitations: Selectivity and sensitivity of
individual serum bile acid levels in hepatic
dysfunction 178
Samy A. Azer, Geoffrey W. McCaughan and
Neill H. Stacey
15. Hepatic Bilirubin Metabolism: Physiology and
pathophysiology 204
Yukihiko Adachi and Toshinori Kamisako
16. Hepatotrophic Activities of HGF in Liver
Regeneration after Injury and the Clinical
Potentiality for Liver Diseases 220
Uichi Koshimizu, Kunio Matsumoto and
Toshikazu Nakamura
17. Apoptosis in Liver 230
Akira Ichihara
Liver and Environmental Xenobiotics
S.Y.S. Rana and K. Taketa (Eds)
Copyright © 1997. Narosa Publishing House. New Delhi. India
I. Extracellular Matrix in Liver
P.R. Sudhakaran, N. Anil Kumar and Anitha Santhosh
Department of Biochemistry. University of Kerala. Trivandrum. India
Introduction
The extracellular matrix is a complex network of macromolecules that
interact with one another as well as with cells in tissues. It comprises both
interstitial stroma and the basement membrane that surround the epithelial
tissues. nerves. fat cells and muscle. The major components of the extracellular
matrix (ECM) in various tissues are collagen. elastins. proteoglycans and
glyco-proteins such as fibronectin, laminin. nidogen. entactin. tenascin etc.
Apart from providing physical support to hold cells and tissues together.
the ECM provides a highly organised lattice within which the cells can
migrate and interact with one another. The interactions of cells with the
ECM are critically important in the embryonic development. growth regulation
and differentiation. The composition of ECM interacting with cell surface
has important regulatory and structural consequences for cells and an extensive
literature now documents these biological roles. The proportion of the ECM
and the connective tissue in relation to the parenchymal tissue is very small
in liver. Nevertheless, the tasks which the ECM of the liver have to fulfil
are complex. It has to combine maximum mechanical stability with minimum
hindrance to the free transport of proteins and metabolites between
parenchymal cells and the blood stream. In this chapter a brief review on
the composition and distribution of extracellular matrix in liver. the interaction
of liver cells with the components of the ECM and the biological consequences
of these interactions, is presented.
Hepatic Parenchyma
Liver is a vital organ involved in a series of physiological functions in
vertebrates. Some of the major functions include: synthesis and secretion
of plasma proteins and bile; absorption. utilisation. storage and redistribution
of nutrients derived from diet; detoxification of potentially harmful xenobiotic
substances. By virtue of its unique and strategic positioning between blood
plasma and bile. hepatocytes. the main epithelial type of cell in liver is
carrying out these diverse group of activities [I]. The organisation of hepatic
parenchyma is different from other epithelia and is described as a continuum
2 SUDHAKARAN ET AL
of hepatocytes arranged in I-cell thick plates separated by blood sinusoidal
spaces. In the livers of birds, amphibians and certain fishes, the hepatocytes
are arranged in 2-cell thick plate instead of one. In human liver, the plates
are several cell thick at birth forming what is known as a muralium multiplex,
which then gradually remodels to a I-cell thick muralium simplex within
the first several years of postnatal life [2].
Hepatocytes constitute more than 90% of the liver mass in most mammalian
species. It is a polyhedral cell whose shape ranges from heptahedral to
dodecahedral, depending upon its placement within the liver muralium [2].
Unlike simple epithelial cells, hepatocytes in adult liver is structurally and
functionally polarised and has three distinct membrane domains, sinusoidal
(basal), lateral and canalicular (apical). Functional polarisation of hepatocytes
is evident in the secretion of bile into bile duct by traversing the apical
surface whereas albumin is secreted into circulation by traversing the
sinusoidal surface [3, 4]. Sinusoids are modified capillaries which carry
blood from portal vein and hepatic artery to the central vein and are lined
by discontinuous, fenestrated endothelium. Other than endothelial cells, the
major type of nonparenchymal cells are Kupffer cells (resident macrophages
in sinusoidal lumen) and fat storing Ito cells residing in peri-sinusoidal
space of Disse. Canalicular surfaces form the bile canalicular network that
transports bile. Lateral plasma membrane fuse along side bile canaliculi to
form tight junctions that occlude the apical domain from the basolateral
surface. Intermediate junctions, desmosomes and gap junctions on lateral
domains provide cohesive strength and functional communication between
hepatocytes.
Hepatic Matrix
Unlike the classical epithelium, hepatocytes have a belt of apical surtace
dividing the two basolateral surfaces that are in contact with the ECM.
Although there is no morphologically identifiable basement membrane close
to the putative basal surface of the hepatocytes, the sinusoids contain typical
matrix components that appear to contact the sparse endothelial cells as
well as the hepatocytes and these components are found elsewhere through
the tissue indicating that the ECM is a structurally important component in
liver [5-9]. Characterisation and distribution of ECM in liver have been
studied by biochemical and immunocytochemical methods [5-8, 10-11].
The major types of collagens are Col. I, ill and IV. The matrix glycoproteins,
fibronectin and laminin and heparan sulphate proteoglycan are also present.
Ultrastructural localization studies in mouse liver revealed the presence of
typical collagen fibrils and small bundles in portal tracts and Disse's space.
Col. I is present in liver capsule, portal stroma and in the perisinusoidal
space indicating a structural role supporting the hepatocyte layer at the
intralobular regions. Col. type III appears to be present only in stroma in
liver and is not in direct contact with hepatocyte surface. Basal surface of