Description of pathogenesis of paraquat induced mucosal injury
Paraquat, as all bipyridyl salts, is caustic in nature. After ingestion, the local corrosive effects of paraquat cause erythema, irritation to the oral and gastrointestinal mucosa; this further worsens to ulceration and sloughing of the mucosa. The cellular effects of paraquat are exerted due to redox cycling leading to the formation of reactive oxygen species, whose concentration increases significantly in time, which can lead to a situation described as oxidative stress. This phenomenon occurs when there is an overproduction of reactive oxygen species, the high overwhelm the natural radical blocking or scavenging mechanisms of the existing antioxidant defense systems. This intracellular oxidative stress is generated by accumulation of superoxide anion, hydrogen peroxide, and hydroxyl radicals within the cells. Destructive actions of reactive oxygen species on the cells include: free radical-mediated lipid oxidation leading to production of phospholipid peroxides, oxidative damage of proteins, carbohydrates and nucleic acids.8 9. The effects eventually lead to the subsequent disruption of cellular metabolism, apoptosis and finally programmed cell death. These effects eventually cause epithelial thinning and mucosal damage. Therefore, this oxidative stress process also plays a key role in the associated subsequent mucosal (oral and gastrointestinal) damage caused by paraquat. Another complication that arises from the over accumulation of reactive oxygen species is inflammation. This activate transcription factors which results in upregulation of pro-inflammatory cytokines, cytokines modulators, adhesion molecules, and stress responders. This amplification causes a cycle of constant production of cytokines that result in further damage and ulceration of the mucosa and increases pain and discomfort.10 14
Another precipitating factor in the extent and severity of oral mucosal injury is microbial colonization of the ulcers and the damaged mucosa. The oral cavity is coated by a plethora of bacteria, and some of these bacteria are harmful and are implicated in oral diseases (caries and periodontitis) and several systemic diseases.13 Most ulcers are covered by a whitish pseudomembrane composed of dead cells and fibrin. The pseudomembrane creates a favorable environment for bacterial colonization by both Gram-positive and Gram-negative organisms. Secondary infections caused by the bacteria and by-products of bacterial metabolism further intensifies mucosal inflammation, leading to further damage.15 Figure 1