Acetaldehyde-Related Pathology

Part of the prestigious Novartis Foundation, this is the first book to review the pathology associated with acetaldehyde, a known toxic agent found in cigarette smoke and other pollutants and derived from ingested alcohol, amongst other sources. In the body, acetaldehyde affects several tissues, particularly the brain and liver, causing various diseases, including cancer, alcoholic liver disease and Alzheimer’s.

Acetaldehyde-Related Pathology describes the toxic effects of acetaldehyde at the tissue and cellular levels, reviewing enzyme biochemistry, transgenic mouse models of alcohol dehydrogenase mutants, and the cell-signalling pathways implicated in alcohol-related pathology. It explores the mechanisms of acetaldehyde-induced damage to tissues, often a first step in carcinogenesis, including the oral cavity, the human airway, and the GI tract. The book considers pharmacological strategies and treatments for reducing oral and intestinal acetaldehyde. Acetaldehyde-Related Pathology features in-depth, round-table discussions by an international array of scientists from major laboratories worldwide involved in studies of acetaldehyde-related pathology.

This book is essential reading for anyone interested in the effects of this compound - pathologists, biochemists, toxicologists, cell and molecular biologists.

Symposium on Acetaldehyde-related pathology: bridging the trans-disciplinary divide, held at the Novartis Foundation, London 5–7th September 2006

Editors: Derek J. Chadwick (Organizer) and Jamie Goode

This symposium is based on a proposal made by Victor Preedy, Peter Emery and Mikko Salaspuro

Peter Emery Chair’s introduction 1

David W. Crabb and Suthat Liangpunsakul Acetaldehyde generating enzyme systems: roles of alcohol dehydrogenase, CYP2E1 and catalase, and speculations on the role of other enzymes and processes 4

Discussion 16

Richard A. Deitrich, Dennis Petersen and Vasilis Vasiliou Removal of acetaldehyde from the body 23

Discussion 40

Shih-Jiun Yin and Giia-Sheun Peng Acetaldehyde, polymorphisms and the cardiovascular system 52

Discussion 63

Jun Ren Acetaldehyde and alcoholic cardiomyopathy: lessons from the ADH and ALDH2 transgenic models 69

Discussion 76

Mikko Salaspuro Interrelationship between alcohol, smoking, acetaldehyde and cancer 80

Discussion 89

Hiroto Matsuse, Chizu Fukushima, Terufumi Shimoda, Sadahiro Asai and Shigeru Kohno Effects of acetaldehyde on human airway constriction and inflammation 97

Discussion 106

Helmut K. Seitz The role of acetaldehyde in alcohol-associated cancer of the gastrointestinal tract 110
Discussion 119

Robert Tardif The determination of acetaldehyde in exhaled breath 125

Discussion 133

Mostofa Jamal, Kiyoshi Ameno, Mitsuru Kumihashi, Weihuan Wang, Ikuo Uekita and Iwao Ijiri Ethanol and acetaldehyde: in vivo quantitation and effects on cholinergic function in rat brain 137

Discussion 141

Ville Salaspuro Pharmacological treatments and strategies for reducing oral and intestinal acetaldehyde 145

Discussion 153

Victor R. Preedy, David W. Crabb, Jaume Farrés and Peter W. Emery Alcoholic myopathy and acetaldehyde 158

Discussion 177

Onni Niemelä Acetaldehyde adducts in circulation 183

Discussion 193

General discussion 198

M. Apte, J. McCarroll, R. Pirola and J. Wilson Pancreatic MAP kinase pathways and acetaldehyde 200

Discussion 211

Shivendra D. Shukla, Youn Ju Lee, Pil-hoon Park and Annayya R. Aroor Acetaldehyde alters MAP kinase signalling and epigenetic histone modifications in hepatocytes 217

Discussion 224

Paul J. Thornalley Endogenous „´-oxoaldehydes and formation of protein and nucleotide advanced glycation endproducts in tissue damage 229

Discussion 243

C. J. Peter Eriksson Measurement of acetaldehyde: what levels occur naturally and in response to alcohol? 247

Discussion 256

Final discussion 261

Contributors Index 265

Subject index 267

"…will be found on the shelves of most scientific biomedical libraries." (Doody's Book Reviews) The Novartis Foundation is an international scientific and educational charity which promotes the study and general knowledge of science and in particular encourages international co-operation in scientific research.
Chairman: Peter Emery Acetaldehyde contributes to pathologies ranging from cancer to asthma. It affects the whole body, the architecture of the cell and molecular control mechanisms. The origins of acetaldehyde vary from bacteria in the oral cavity and intestinal tract to atmospheric acetaldehyde as an environmental pollutant. Significant amounts of acetaldehyde are also derived from cigarette smoke and alcohol, both of which are major contributors to disease globally.

Acetaldehyde has deleterious effects in the liver, brain and skeletal muscle. It has also been shown that bacteria can generate significant amounts of acetaldehyde in the gastrointestinal tract, thus contributing to carcinogenesis in this tissue. Many of the toxic effects of ethanol ingestion are mediated through acetaldehyde and there is increasing awareness that acetaldehyde is a principal disease-forming agent in tobacco-related illnesses.

Alcohol is metabolized by conversion to acetaldehyde, which in turn is converted to acetate by aldehyde dehydrogenase (ALDH). There are a number of forms of ALDH of which the mitochondrial isoform (ALDH2) is particularly important. The ALDH2 gene has a functional polymorphism: homozygous subjects have little or no ALDH2 activity compared to their wild-type counterparts. Heterozygotes generally also have low ALDH2 activity. Epidemiological studies have found increased risk of certain diseases, including cancer of the gastrointestinal tract, alcoholic liver disease and late-onset Alzheimer’s disease in subjects with ALDH2 deficiency.

This book features contributions from researchers working on all aspects of acetaldehyde-related pathology. From their expert accounts and the lively discussions accompanying each chapter, we can derive a better understanding of the pathogenesis of diseases in which acetaldehyde, from whichever source, is implicated.