Nitrative and Oxidative Stress in Toxicology and Disease

Abstract

Persistent inflammation and the generation of reactive oxygen and nitrogen species play pivotal roles in tissue injury during disease pathogenesis and as a reaction to toxicant exposures. The associated oxidative and nitrative stress promote diverse pathologic reactions including neurodegenerative disorders, atherosclerosis, chronic inflammation, cancer, and premature labor and stillbirth. These effects occur via sustained inflammation, cellular proliferation and cytotoxicity and via induction of a proangiogenic environment. For example, exposure to the ubiquitous air pollutant ozone leads to generation of reactive oxygen and nitrogen species in lung macrophages that play a key role in subsequent tissue damage. Similarly, studies indicate that genes involved in regulating oxidative stress are altered by anesthetic treatment resulting in brain injury, most notable during development. In addition to a role in tissue injury in the brain, inflammation, and oxidative stress are implicated in Parkinson's disease, a neurodegenerative disease characterized by the loss of dopamine neurons. Recent data suggest a mechanistic link between oxidative stress and elevated levels of 3,4-dihydroxyphenylacetaldehyde, a neurotoxin endogenous to dopamine neurons. These findings have significant implications for development of therapeutics and identification of novel biomarkers for Parkinson's disease pathogenesis. Oxidative and nitrative stress is also thought to play a role in creating the proinflammatory microenvironment associated with the aggressive phenotype of inflammatory breast cancer. An understanding of fundamental concepts of oxidative and nitrative stress can underpin a rational plan of treatment for diseases and toxicities associated with excessive production of reactive oxygen and nitrogen species.

A multibiomarker approach in rats to assess the impact of pollution on Sinos River, Southern Brazil

“…Several studies have reported that oxidative stress plays a central role in disease pathogenesis and in tissue damage in response to toxicant exposures (Roberts et al, 2009). For example, Koyu et al (2006) showed that cadmium has an important toxic effect on liver tissue and concluded that cadmium exhibits its toxicity by increasing lipid peroxidation.…”

Resveratrol and health – A comprehensive review of human clinical trials

“…Oxidative stress occurs when an excess of reactive oxygen species (ROS) are generated from any of a variety of sources, including the mitochondrial electron transport chain and reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidases. ROS can damage macromolecules and activate signaling pathways that include a number of inflammatory mediators [43,44]. Inflammation, in turn, can lead to further oxidative stress in a cycle that contributes to the progression of many diseases.…”

“…Inflammation, in turn, can lead to further oxidative stress in a cycle that contributes to the progression of many diseases. Atherosclerosis, diabetes mellitus, chronic obstructive pulmonary disease, and cancer are examples of diseases associated with ROS-induced chronic inflammation [43,45,46]. Laboratory models suggest these diseases can either be prevented, treated, or cured through attenuating ROS, which may be achieved through treatment with resveratrol [22,47,48].…”

Tumor microenvironment and breast cancer progression

“…95 Curtis recently identified a number of oxidative stress and DNA repair proteins that are needed to prevent the accumulation of ROS and influence the estrogen-responsiveness of MCF-7 breast cancer cells, showing that these proteins may be differentially expressed in normal mammary tissue, DCIS, and IDC. 96 Some authors demonstrated that these oxidative stress proteins form an interactive network, acting collectively to regulate oxidative stress and maintain a functional cellular environment.…”