Current Medicinal Chemistry - Volume 8, Issue 7, 2001

The age-related neurodegenerative diseases exemplified by Alzheimer's disease (AD), Lewy body diseases such as Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease are characterized by the deposition of abnormal forms of specific proteins in the brain. Although several factors appear to underlie the pathological depositions, the cause of neuronal death in each disease appears to Read More

Hypoxia is a feature of some regions of many tumours, ischaemic events, and arthritis. Drugs activated in hypoxia have wide potential application, particularly in overcoming the resistance of hypoxic tumour cells to radiotherapy. Key features of such drugs include redox properties appropriate for activation by reductase enzymes (typically flavoproteins), and oxygen-sensitive reduction chemistry such that normal levels of oxyge Read More

Reactive oxygen (ROS) and reactive nitrogen species (RNS) produced in vivo at levels that cannot be dealt with adequately by endogenous antioxidant systems can lead to the damage of lipids, proteins, carbohydrates and nucleic acids. Oxidative modification of these molecules by toxic levels of ROS and RNS represents an extreme event that can lead to deleterious consequences such as loss of function. More recently, h Read More

For more than half a century, numerous proposals have been advanced for the mode of action of carcinogens. This review presents a wide array of evidence that implicates oxidative stress (OS) in many aspects of oncology, including: formation of reactive oxygen species (ROS) by the major classes of carcinogens (as well as minor ones), cancer stages, oncogene activation, aging, genetic and infectious illnesses, nutrition, and Read More

In order to ascertain the role of dietary flavonoids as antioxidants in vivo it is necessary to understand the chemical nature of the absorbed forms in the circulation in vivo and how the multiplicity of research findings in vitro reflect the bioactivity of flavonoids in vivo. Only when we gain adequate information on the circulating forms can we begin to understand the targeting to the tissues, whether flavonoids cross the blood-brain b Read More

Parkinson's disease occurs in 1percent of people over the age of 65 when about 60percent of the dopaminergic neurons in the substantia nigra of the midbrain are lost. Dopaminergic neurons appear to die by a process of apoptosis that is induced by oxidative stress. Oxygen radicals abstract hydrogen from DNA forming DNA radicals that lead to DNA fragmentation, activation of DNA protective mechanisms, NAD depletion and Read More

Oxidative stress in brain is emerging as a potential causal factor in aging and age-related neurodegenerative disorders. Brain tissue from living patients is difficult to acquire; hence, animal models of aging and age-related neurodegenerative disorders, though not perfect models, have provided tissue to study the role of oxidative stress in these disorders. In this review, the central role of oxidative damage in brain in mo Read More

Increased aerobic metabolism during exercise is a potential source of oxidative stress. In muscle, mitochondria are one important source of reactive intermediates that include superoxide,hydrogen peroxide, and possibly hydroxyl radical . The recent discovery that mitochondria may generate nitric oxide also has implications for oxidant production and mitochondrial function. In this review, we critically examine the co Read More

Redox cycling of catecholestrogen metabolites between quinone and catechol forms is a mechanism of generating potentially mutagenic oxygen radicals in estrogen-induced carcinogenesis. Consistent with this concept, multiple forms of oxygen radical-generated DNA damage are induced by estrogen in cell-free systems, in cells in culture and in rodents prone to estrogen-induced cancer. Metal ions, specifically iron, are necess Read More

Impairment of normal spermatogenesis and sperm function are the most common causes of male factor infertility. Abnormal sperm function is difficult to evaluate and treat. There is a lack of understanding of the factors contributing to normal and abnormal sperm function leading to infertility. Many recent studies indicate that oxygen-derived free radicals induce damage to spermatozoa. The excessive generation of t Read More

Reproductive toxicity has been a topic of increasing interest and concern in recent years, generating controversy in association with danger to humans and other living things. A veritable host of chemicals is known to be involved, encompassing a wide variety of classes, both organic and inorganic. Exposure is pervasive and virtually unavoidable due to contamination of air, water, ground, food, beverages, drugs, and hous Read More