Indirect oxidative stress from pulmonary inflammation exceeds direct oxidative stress from chemical damage to mitochondria. (22nd April 2019)

• Record Type: Journal Article
• Authors: Smith, Carr J; Perfetti, Thomas A; King, Judy A
• Is Part Of: Toxicology research and application. Volume 3(2019)
• Publication Date: 2019-04-22
• Subjects: Oxidative stress -- inflammation -- pulmonary -- mitochondria -- direct versus indirect; Toxicology -- Periodicals; 571.9505
• DOI: 10.1177/2397847319842845
• Languages: English
• ISSNs: 2397-8473

Abstract

The term oxidative stress was introduced by the National Toxicology Program (NTP) in 1985. It is now invoked as a contributing mechanism to the induction of tumors in chronic rodent cancer bioassays following administration of a chemical agent, especially via inhalation. The term oxidative stress is confusing as there are two different types of oxidative stress. Direct oxidative stress derives from chemical damage to mitochondrial energy-producing structures with concomitantly altered mitochondrial function. Indirect oxidative stress is frequently quantitatively greater than direct oxidative stress in terms of release of activated oxygen or nitrogen species secreted by one or more of 12 potential in situ or recruited inflammatory cell types. Evidence supporting a role for direct oxidative stress in chemical carcinogenesis comes from cell culture studies wherein the cells have been removed from their natural environment and denuded of defense systems, for example, removal of particles by cilia, macrophage engulfment of particles, and suspension and dilution of chemicals or particles in pulmonary surfactant. In contrast, extensive direct evidence from bronchoalveolar lung washes conducted on humans shows elevations in pulmonary macrophage and neutrophil counts, release of intravascular proteins into the extracellular space, and activation of pro-inflammatory cytokines that correlate with observed pulmonary pathology. Higher rates of lung cancer in smokers with chronic obstructive pulmonary disease (COPD) than in smokers at the same cigarette consumption level but without COPD demonstrate a positive contribution by pulmonary inflammation to pulmonary carcinogenesis. Indirect oxidative stress from pulmonary inflammation should be considered before allocating a primary carcinogenic role for direct oxidative stress.