Current Nutrition & Food Science

ISSN: 1573-4013

Current Nutrition & Food Science
Volume 3, Number 3, August 2007

Contents

Oxidative Stress in Disease
Guest Editor: Prof. Alessandro Laviano

Editorial Never Underestimate The Power of ROS - The Controversial Role of Oxidative Stress in Health and Disease Pp. 183


Antioxidant Therapy for the Treatment of Oxidative Stress Associated to Cancer and Cancer- Related Anorexia/Cachexia Pp. 184-193
Giovanni Mantovani, Clelia Madeddu, Antonio Macciò, Elena Massa, Giulia Gramignano and Roberto Serpe
[Abstract]


Oxidative Stress in the Pathogenesis/Treatment of Diabetes and its Complications Pp. 194-199
Ludovica Piconi, Michael A. Ihnat and Antonio Ceriello
[Abstract]


Oxidative Stress in the Pathogenesis/Treatment of Atherosclerosis Pp. 200-208
Francesco Violi and Roberto Cangemi
[Abstract]


Oxidative Stress in the ICU Pp. 209-215
Pierre Singer, Joelle Attal Singer, Haim Shapiro and Shaul Lev
[Abstract]


Poor Nutrition with Aging: An “Oxidatively Stressing” Condition Pp. 216-221
Benedetta Bartali
[Abstract]


How to Keep Oxidative Stress Under Control? Pp. 222-235
Laetitia Pire, Ginette Deby-Dupont, Thierry Lemineur and Jean\ Charles Preiser
[Abstract]


General Articles


Trace Mineral Losses in Sweat Pp. 236-241
Troy D. Chinevere, James P. McClung and Samuel N. Cheuvront
[Abstract]


Nutritional Support in Cancer Pp. 242-248
Paola Costelli, Maurizio Muscaritoli, Fabio Penna, Andrea Bonetto, Valerio Giacomo Minero, Zaira Aversa, Silvia Iannuzzi, Gabriella Bonelli, Francesco M. Baccino and Filippo Rossi Fanelli
[Abstract]




Abstracts


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Editorial

Never Underestimate The Power of ROS - The Controversial Role of Oxidative Stress in Health and Disease
There is general agreement that the most powerful step in the evolution of life on planet Earth was the acquisition of mitochondria, and thus of oxidative phosphorylation, by primordial cells. This achievement provided cells with larger amount of energy, which significantly contributed to the evolution of unicellular organisms into more complex and specialized living forms. However, this progress did not occur without any expenses. The use of oxygen in energy metabolism increased the production of energy as ATP, but toxic and potentially lethal substances were also produced, the reactive oxygen species (ROS), which should be rapidly detoxified to prevent molecular and cellular damages. As a consequence, antioxidant systems developed to counteract the negative effects of ROS, and living organisms adapted to strive by maintaining a specific redox state, i.e. a balance between ROS production and antioxidants’ scavenger activity.

During the last two centuries, the life expectancy significantly increased, mostly because of improved nutrition, since medical advances contributed to this progress when mortality rates had already fallen substantially [1]. However, longer life results in longer exposure to toxic agents, including ROS. Also, age- and/or disease-related inefficiency of antioxidant systems and reduced intake of antioxidants with the diet due to age- and/or disease-related anorexia increase oxidative stress, which in turn may promote molecular damages triggering the onset of degenerative diseases, worsening the clinical condition of patients and preventing healthy aging.

Based on these premises, it is not surprising that considerable scientific efforts have been put into the investigation of the role of oxidative stress in the aging process, in the pathogenesis of degenerative diseases, and in influencing the outcome of patients. Consequently, a large number of papers have been published in these areas during the last few years, making difficult to people not directly involved in the study of oxidative stress to get a comprehensive view of the scientific and clinical problems. In this light, the aim of this special issue of Current Nutrition & Food Science is to provide the readers with an authoritative update on the clinical implications of oxidative stress. Leading researchers in their respective fields reviewed the available evidence to delineate the role of oxidative stress in cancer [2], diabetes [3], atherosclerosis [4], critically ill patients [5] and in the aging process [6]. From their reviews, it appears that oxidative stress play a role in the pathogenesis of many diseases, yet we have very few clues on how we can develop an effective antioxidant therapeutic strategy [7]. Indeed, many clinical trials testing the effects of antioxidant supplementation yielded controversial and even negative results [8], underlying our limited knowledge on the optimal timing and dosing of antioxidant therapy, and even on the best antioxidant(s) to be given.

Therefore, further research should be conducted in order to fully explore the role of oxidative stress in health and disease. Yet, we can say that although oxidative stress is involved in the pathogenesis of many diseases, its complete annihilation may lead to even worse clinical effects. We have evolved and adapted to “symbiotically” leave with mitochondria and mitochondria-related persistent, yet low-grade, oxidative stress, which in turn may contribute to the physiological functioning of the cell. Thus, reducing oxidative stress to levels below the physiological threshold may trigger intracellular signalling pathways further damaging cellular machinery. This could represent a critical area for future scientific investigations, with tremendous social implications. Indeed, vitamin supplements are regularly taken all over the world because their prescription is just based on the media-driven assumption that oxidative stress is harmful for health and supplements are beneficial. However, when considering antioxidant therapy, it should be remembered that “more” not necessarily means “better”.

REFERENCES

[1] Birn AE. Gates’s grandest challenge: transcending technology as public health ideology. Lancet 2005; 366:514-519.

[2] Mantovani G, Madeddu C, Macciò A, Massa E, Gramignano G, Serpe R. Antioxidant therapy for the treatment of oxidative stress associated to cancer and cancer- related anorexia/cachexia. Curr Nutr Food Sci 2007; 3: 184-193.

[3] Piconi L, Ihnat MA, Ceriello A. Oxidative stress in the pathogenesis/treatment of diabetes and its complications. Curr Nutr Food Sci 2007; 3: 194-199.

[4] Violi F, Cangemi R. Oxidative stress in the pathogenesis/treatment of atherosclerosis. Curr Nutr Food Sci 2007; 3: 200-208.

[5] Singer P, Singer JA, Shapiro H. Lev S. Oxidative stress in the ICU. Curr Nutr Food Sci 2007; 3: 209-215.

[6] Bartali B. Poor nutrition with aging: an “oxidatively stressing” condition. Curr Nutr Food Sci 2007; 3: 216-221.

[7] Pire L, Deby-Dupont G, Lemineur T, Preiser JC. How to keep oxidative stress under control? Curr Nutr Food Sci 2007; 3: 222-235.

[8] Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 2007; 297:842-57.


Prof. Alessandro Laviano
Department of Clinical Medicine
Sapienza - University of Rome
Viale dell’Università 37, 00185 Rome,
ITALY
E-mail: alessandro.laviano@uniroma1.it


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Antioxidant Therapy for the Treatment of Oxidative Stress Associated to Cancer and Cancer- Related Anorexia/Cachexia
Giovanni Mantovani, Clelia Madeddu, Antonio Macciò, Elena Massa, Giulia Gramignano and Roberto Serpe

Cancer-related anorexia/cachexia syndrome (CACS) is a complex phenomenon: metabolic abnormalities, proinflammatory cytokines produced by the host immune system, circulating tumor-derived catabolic factors, decreased food intake, and probably additional unknown factors, all play different roles. This review examines the pathophysiology and the mechanisms linking CACS and Oxidative Stress (OS) in cancer. On the basis of several of our previously published studies and our clinical experience we have developed an innovative treatment approach wich consists of an integrated nutritional and pharmacological treatment. This treatment approach of CACS/OS based on multiple components, each targeted at the different factors involved, may be effective both in improving objective clinical symptoms, including lean body mass, and subjective symptoms, including quality of life.


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Oxidative Stress in the Pathogenesis/Treatment of Diabetes and its Complications
Ludovica Piconi, Michael A. Ihnat and Antonio Ceriello

In diabetes oxidative stress plays a key role in the pathogenesis of vascular complications, and an early step of such damage is considered the development of an endothelial dysfunction. Hyperglycemia directly promotes an endothelial dysfunction inducing process of overproduction of superoxide and consequently peroxynitrite that damages DNA and activates the nuclear enzyme poly(ADP-ribose) polymerase. This process, depleting NAD+, slowing glycolisis, ATP formation and electron transport, results in acute endothelial dysfunction in diabetic blood vessels and contributes to the development of diabetic complications.

These new findings may explain why classical antioxidants, like vitamin E, that work scavenging already formed toxic oxidation products, have failed to show beneficial effects on diabetic complications, and suggest new and attractive “causal” antioxidant therapy. New, low molecular mass compounds that act as SOD or catalase mimetics or L-propionyl-carnitine and lipoic acid, that work as intracellular superoxide scavengers, improving mitochondrial function and reducing DNA damage, may be good candidates for such strategy, and preliminary studies support this hypothesis. This “causal” therapy would also be associated with other promising tools such as LY 333531, PJ34 and FP15, which block protein kinase β isoform, poly(ADP-ribose) polymerase and peroxynitrite, respectively. It is now evident that, statins, ACE inhibitors, AT-1 blockers, calcium channel blockers and thiazolinediones have a strong intracellular antioxidant activity, and it has been suggested that many of their beneficial ancillary effects are due to this property. This preventive activity against oxidative stress generation can justify a large utilization and association of this compounds for preventing complications in diabetic patients where antioxidant defences have been shown to be defective.


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Oxidative Stress in the Pathogenesis/Treatment of Atherosclerosis
Francesco Violi and Roberto Cangemi

Oxidative stress seems to play a key-role in the pathogenesis of atherosclerosis. Intracellular ROS (reactive oxygen species) have been increasingly appreciated to have a role in this context. ROS seem to mediate various signaling pathways that underlie atherogenesis, from the initiation of fatty streak development through lesion progression to ultimate plaque rupture. Moreover enhanced oxidative stress has been found in many of the classical risk factors for cardiovascular disease.

However some issues remain to be clarified. Agents that prevent LDL from oxidation have been shown in a range of in vitro and animal models to reduce the development and progression of atherosclerosis, but most of the trials with antioxidants, planned in the last years in patients with cardiovascular disease, have given equivocal results. The reason for the disappointing findings is unclear but one possible explanation is the lack of identification criteria of patients who are potentially candidates for antioxidant treatment.

In this review we focused on potential source of ROS in atherosclerotic disease, the relationship between ROS generation and atherosclerotic progression and the potential role of antioxidants.


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Oxidative Stress in the ICU
Pierre Singer, Joelle Attal Singer, Haim Shapiro and Shaul Lev

The critically ill patient is undergoing episodes of ischemia reperfusion, systemic inflammatory response syndrome, sepsis and multiorgan failure. These episodes are associated with lower levels of antioxidants in specific populations such as acute pancreatitis, head trauma, acute respiratory distress syndrome (ARDS) or acute lung injury patients. This review will deal with the definition of oxidative stress, the reactive oxygen species that are produced by the tissues during the oxidative stress, the antioxidant capacity of the ICU patients, but also the role of the glucose control in the regulation of anti oxidant therapy in addition to trace elements, vitamins and N-acetyl-cysteine. A special accent will be given to supplements such as polyphenols for the prevention and the therapy of oxidative stress in specific situations such as organ transplantation or hemorrhagic shock.


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Poor Nutrition with Aging: An “Oxidatively Stressing” Condition
Benedetta Bartali

A large proportion of community-living older persons have a deficient intake of nutrients according to the Recommended Dietary Allowance but the prevalence of undernutrition is frequently underestimated. A low dietary intake of antioxidants may alter the balance between oxidants and antioxidants and lead to oxidative stress, which has been associated with dysregulation of cellular and immune function, increased levels of markers of inflammation, muscle and neural damage and the development of clinical conditions. Previous studies showed an association between poor nutrition and frailty and disability in older persons and suggested that oxidative stress plays a central role in this pathway. This review summarizes the evidence that: 1) the older population is particularly prone to undernutrition; and 2) poor nutrition in older persons represents an “oxidatively stressing condition” that may lead to the development of important adverse outcomes such as frailty and disability. A conceptual framework for this hypothesized link between poor nutrition and frailty and disability in older persons is presented. More attention on nutritional status in older persons could represent an important window of opportunity to reduce or postpone the detrimental consequences related to oxidative stress.


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How to Keep Oxidative Stress Under Control?
Laetitia Pire, Ginette Deby-Dupont, Thierry Lemineur and Jean Charles Preiser

An excessive production of oxidants disturbs the normal intracellular equilibrium, and can lead to an “oxidative stress”. Recent data indicate that several components of the regular diet as well as chemical compounds and drugs can modulate the so-called “oxidative stress” both via anti-oxidant effects and via inhibition or activation of the enzymes involved in reactive nitrogen oxygen species (RNOS).

We will describe in this review article the biochemistry of oxygen, the physiological roles and regulation of oxidative stress. The clinical relevance of uncontrolled oxidative stress will be presented as well as the results of therapeutic trials with antioxidants. New promising strategies which modulate the activities of the RNOS generating enzymes, with selected catalytic inhibitors will be discussed.


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Trace Mineral Losses in Sweat
Troy D. Chinevere, James P. McClung and Samuel N. Cheuvront

Copper, iron and zinc are nutritionally essential trace minerals that confer vital biological roles including the maintenance of cell structure and integrity, regulation of metabolism, immune function, oxygen transport, and muscle and central nervous system function. Dietary Reference Intakes (DRIs) for these minerals are useful for the general population, but these guidelines may be inadequate for some populations (e.g., soldiers, athletes) who experience copious sweating due to high physical activity levels and/or frequent exposure to extreme environmental conditions. The trace mineral content of sweat may predispose these populations to subclinical/clinical nutritional deficiencies. Studies on sweat trace mineral losses report highly variable results. Much of the variability may be methodological. Non-standardization of collection techniques, collection sites (local versus whole body), and numerous other variables cloud definitive conclusions on sweat trace mineral losses. The objectives of this manuscript are to 1) review the literature on sweat copper, iron, and zinc losses, 2) present the potential sources of variability, 3) interpret findings in relation to nutritional needs, and 4) identify directions for future research.


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Nutritional Support in Cancer
Paola Costelli, Maurizio Muscaritoli, Fabio Penna, Andrea Bonetto, Valerio Giacomo Minero, Zaira Aversa, Silvia Iannuzzi, Gabriella Bonelli, Francesco M. Baccino and Filippo Rossi Fanelli

The management of cancer patients is frequently complicated by the occurrence of cachexia, a complex syndrome characterized by marked depletion of body weight, associated with profound alterations of both nutritional status and metabolic homeostasis. Progressive wasting of skeletal muscle mass and adipose tissue is a typical feature of cancer cachexia. This syndrome has a large impact on morbidity and mortality, and significantly affects patients’ quality of life. On this line, understanding the pathogenic mechanisms of cachexia is of crucial importance to define targeted therapeutic strategies.

Many studies have addressed the relevance of nutritional interventions in cancer hosts. In particular, it has been shown that malnutrition in cancer patients can be delayed when nutritional supplementation is adopted early in the course of the disease. The preservation of a good nutritional status, in particular when it is achieved concurrently with specific antineoplastic treatment, will prevent or at least delay the onset of overt cachexia, allowing the use of more aggressive therapeutic regimens. This paper will review the relevant literature, focusing on those options that have shown more promising for the clinical practice.