Abstract This chapter describes several situations in which free radicals/reactive species (RS) are especially problematic and require special protective mechanisms. The first is the gastrointestinal tract, which is exposed to pro-oxidants from the diet and must protect itself from oxidative damage using a range of antioxidants. It also produces some RS for useful purposes, including the regulation of bacterial colonization, by NADPH oxidase enzymes. The respiratory tract has to cope with inhaled air pollutants (O3, NO2, SO2, and O2 itself) and contains many antioxidants (especially GSH) in its lining fluids and cells. The relation of antioxidants (especially vitamin C) to asthma is also reviewed. Erythrocytes have special problems because of the haemoglobin they carry, which can oxidize to generate superoxide. Hence erythrocytes are rich in antioxidants. The effects of toxins (e.g. favism), glucose-6-phosphate dehydrogenase deficiency, and infection with malaria parasites on oxidative damage in erythrocytes are presented. Indeed, malaria can be treated with drugs that impose oxidative stress, such as artemisinin. Plants are discussed in detail, including the mechanisms of photosynthetic O2 production, how plants protect themselves against O2 toxicity (using many antioxidants, especially carotenoids), and how they can be damaged by poisons such as paraquat, air pollutants, atrazine, or oxyfluorfen. The problems of the ear and the involvement of RS in hearing loss are discussed. Conception (spermatozoa, ova), pregnancy, embryonic development, normal birth, and premature birth, and the action of teratogens are also considered in the free-radical/antioxidant context, as are the potential benefits and harm from exercise.
Oxidative Stress: Oxidants and Antioxidants, Helmut Sies, editor, Academic Press, 1991, xxii + 650 pages. £76 ($150)Oxygen Chemistry D.T. Sawyer Oxford University Press, England, E30, xiii + 223 pages
The production of superoxide and nitric oxide individ- ually has been associated with the development of several diseases but only recently has it been realised that interactions between them may also be important in disease pathology. The central hypothesis which is emerging is that the balance between nitric oxide and superoxide generation is a critical determinant in the aetiology of many human diseases including atherosclerosis, neu- rodegenerative disease, ischaemia-reperfusion and cancer. These ideas are discussed in this short overview and placed in the context of the current and future status of therapies which could modulate the balance between nitric oxide and superoxide. Key worv Superoxide; Reactive nitrogen species: Peroxynitrite; Oxygen radicals
The ability of oxyhaemoglobin and methaemoglobin to generate hydroxyl radicals (OH.) from H2O2 has been investigated using deoxyribose and phenylalanine as 'detector molecules' for OH.. An excess of H2O2 degrades methaemoglobin, releasing iron ions that react with H2O2 to form a species that appears to be OH.. Oxyhaemoglobin reacts with low concentrations of H2O2 to form a 'reactive species' that degrades deoxyribose but does not hydroxylate phenylalanine. This 'reactive species' is less amenable to scavenging by certain scavengers (salicylate, phenylalanine, arginine) than is OH., but it appears more reactive than OH. is to others (Hepes, urea). The ability of haemoglobin to generate not only this 'reactive species', but also OH. in the presence of H2O2 may account for the damaging effects of free haemoglobin in the brain, the eye, and at sites of inflammation.
The brain has a high oxygen consumption and is rich in oxidizable substrates, mainly catecholamines and unsaturated lipids. Much interest has been shown recently in ‘oxygen radicals’ as mediators of the action of certain neurotoxins, in the role of vitamin E in the nervous system and in the possible use of anti-oxidants in treating degenerative diseases of the nervous system and the consequences of ischaemia. The purpose of this brief review is to explain some of the scientific background to these developments.
Time for primary review 27 days. It is widely agreed that increased consumption of fruits, grains and vegetables, decreased intake of saturated fats, a moderate degree of exercise and perhaps judicious consumption of red wine or other alcoholic beverages (or even tea) would improve the cardiovascular health of the populations in most developed and ‘near-developed’ countries [1–8]. Fruits, grains, teas, vegetables and red wines are rich in antioxidants (ascorbate, tocopherols, tocotrienols, flavonoids, other phenols and carotenoids are among the antioxidants found in various plants consumed by humans; reviewed in [9]), and so it is widely thought that antioxidants make an important contribution to this cardiovascular protective effect [9–14]. This assumption is logical, because there is good evidence that oxidative damage contributes to the pathology of atherosclerosis and vascular dysfunction generally, and that free radicals are involved in myocardial ischemia-reperfusion injury [9,15–20]. However, intervention trials with vitamin E that assess clinical end-points are giving a confused picture [21–23]. Indeed, foods and beverages derived from plants are chemically complex, and cardiovascular protective effects could also arise from many other components or mixtures of components present, including fibre, immunostimulatory agents, monounsaturated fatty acids, agents that modulate cholesterol synthesis, B-vitamins, folic acid, agents modulating nitric oxide production, and even the humble ethanol molecule itself [2,3,5,6,14,24–29]. One obvious way to assess the contribution of antioxidants to the cardiovascular protective effects of the above diets is to conduct intervention trials with single antioxidants, or combinations of a few antioxidants. For example the intervention trials with β-carotene convincingly demolished the concept that this carotenoid is an important anti-cancer agent in humans, at least in smokers [30]. Hence high plasma levels of β-carotene are negatively associated with cancer incidence because both are a consequence of eating a good diet; β-carotene is not …
We propose that the diet-derived compound ergothioneine (ET) is an important nutrient in the human body, especially for maintenance of normal brain function, and that low body ET levels predispose humans to significantly increased risks of neurodegenerative (cognitive impairment, dementia, Parkinson's disease) and possibly other age-related diseases (including frailty, cardiovascular disease, and eye disease). Hence, restoring ET levels in the body could assist in mitigating these risks, which are rapidly increasing due to ageing populations globally. Prevention of neurodegeneration is especially important, since by the time dementia is usually diagnosed damage to the brain is extensive and likely irreversible. ET and vitamin E from the diet may act in parallel or even synergistically to protect different parts of the brain; both may be "neuroprotective vitamins". The present article reviews the substantial scientific basis supporting these proposals about the role of ET.
No abstract is provided for this article.
: Resveratrol is a naturally occurring polyphenolic compound commonly found in plant‐derived products, including red wine. A large number of beneficial effects including anticarcinogenic action and protection from atherosclerotic disease have been attributed to resveratrol. Increased resveratrol intake has been suggested as an explanation for the beneficial effects of moderate red wine consumption. Resveratrol also consistently extends the mean and maximum life span in model organisms including nematode worms. It has been suggested that resveratrol exerts its life‐span–extending effect through calorie restriction or hormesis mimetic effects. We have characterized the effect of resveratrol on stress resistance, developmental rate, growth, and fecundity in the nematode worm Caenorhabditis elegans in order to determine whether the beneficial effects of resveratrol on life span are associated with trade‐offs in terms of early life fitness in nematodes. We find that resveratrol treatment increases stress resistance, specifically to oxidative stress, and causes a small but significant decrease in fecundity early in life without affecting overall fecundity. Resveratrol increased mean and maximum life span by delaying the onset of the exponential increase in mortality characterizing the “dying phase” in C. elegans , but did not affect the dying phase itself, suggesting that it did not act by directly affecting metabolism .
No abstract is provided for this article.
Background and Purpose— We observed recently that elevated plasma cysteine levels are associated with poor clinical outcome in acute stroke patients. In a rat stroke model, cysteine administration increased the infarct volume apparently via its conversion to hydrogen sulfide (H 2 S). We therefore investigated the effects of H 2 S and the inhibition of its formation on stroke. Methods— Cerebral ischemia was studied in a rat stroke model created by permanent occlusion of the middle cerebral artery (MCAO). The resultant infarct volume was measured 24 hours after occlusion. Results— Administration of sodium hydrosulfide (NaHS, an H 2 S donor) significantly increased the infarct volume after MCAO. The NaHS-induced increase in infarct volume was abolished by the administration of dizolcilpine maleate (an N -methyl- d -aspartate receptor channel blocker). MCAO caused an increase in H 2 S level in the lesioned cortex as well as an increase in the H 2 S synthesizing activity. Administration of 4 different inhibitors of H 2 S synthesis reduced MCAO-induced infarct volume dose dependently. The potency of these inhibitors in effecting neuroprotection in vivo appeared to parallel their potency as inhibitors of H 2 S synthesis in vitro. It also appeared that most of the H 2 S synthesizing activity in the cortex results from the action of cystathionine β-synthase. Conclusions— The present results strongly suggest that H 2 S plays a part in cerebral ischemic damage after stroke. Inhibition of H 2 S synthesis should be investigated for its potential as a novel neuroprotective stroke therapy.
